Materiały źródłowe

• #1 What causes Prader-Willi syndrome (PWS)? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  http://www.nichd.nih.gov/health/topics/prader-willi/conditioninfo/causes

  Prader-Willi syndrome is caused by genetic changes on an „unstable” region of chromosome 15 that affects the regulation of gene expression, or how genes turn on and off. […] The genetic changes that cause Prader-Willi syndrome occur in a portion of the chromosome, referred to as the Prader-Willi critical region (PWCR), around the time of conception or during early fetal development. […] Although Prader-Willi syndrome is genetic, it usually is not inherited and generally develops due to deletions or partial deletions on chromosome 15. […] A majority of PWS cases result from a deletion in one region of the father’s chromosome 15 that leads to a loss of function of several genes. […] The corresponding mother’s genes on chromosome 15 are always inactive and thus cannot make up for the deletion on the father’s chromosome 15.

• #2 Prader-Willi syndrome – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/symptoms-causes/syc-20355997

  Prader-Willi syndrome is a genetic condition that is caused by an error in one or more genes. Although it’s not known exactly what causes Prader-Willi syndrome, the problem lies in the genes in a region of chromosome 15. […] Prader-Willi syndrome occurs because certain paternal genes that should be expressed aren’t because: […] A missing or changed gene on chromosome 15 disrupts how a portion of the brain called the hypothalamus typically works. This part of the brain controls the release of hormones. A hypothalamus that isn’t working properly can affect hunger, growth, sexual development, body temperature, mood and sleep. […] In most cases, a random gene change that isn’t inherited causes Prader-Willi syndrome. Finding which gene change caused Prader-Willi syndrome can help with genetic counseling.

• #3 Prader-Willi syndrome | Genetics in Medicine

  https://www.nature.com/articles/gim0b013e31822bead0

  Prader-Willi syndrome is due to absence of paternally expressed imprinted genes at 15q11.2-q13 through paternal deletion of this region (6575% of individuals), maternal uniparental disomy 15 (2030%), or an imprinting defect (13%). […] The absence of expression of one or more of the paternally inherited genes must contribute to the phenotype of PWS. This lack of expression occurs by three primary mechanisms: (i) deletion of a 56 Mb region from the paternally contributed chromosome 15 (found in 6575% of affected individuals); (ii) maternal uniparental disomy (UPD) 15 (found in 2030%); and (iii) a defect in the genomic region that controls the imprinting process, a so-called imprinting defect (ID; 13%). […] The genomic and epigenetic changes causing PWS all lead to a loss of expression of the normally paternally expressed genes on chromosome 15q11.2-q13. Absence of the paternally inherited copy of these genes, or failure to express them, causes total absence of expression for those genes in the affected individual because the maternal contribution for these genes has been programmed by epigenetic factors to be silenced.

• #4 Prader–Willi syndrome | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg2008165

  Three major genetic causes exist: 57Mb deletion of the paternally inherited chromosomal 15q11.2q13 region, maternal uniparental disomy 15, and a defect in the imprinting process in the 15q11.2q13 region on the paternally inherited chromosome. […] PWS is an example of a genomic disorder, as it results from altered genomic structure (an epigenetic phenomenon) and not a specific DNA sequence change. The various genomic changes causing PWS all lead to loss of expression of the paternally expressed genes on chromosome 15q11.2q13 through loss or failure of expression because the maternal contribution has been programmed by epigenetic factors (eg, DNA methylation) to be silenced. […] Most cases of PWS result from a deletion of 57Mb in 15q11.2q13. This region is highly complex and contains a number of imprinted and non-imprinted genes.

• #5 What causes Prader-Willi syndrome (PWS)? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  http://www.nichd.nih.gov/health/topics/prader-willi/conditioninfo/causes

  Prader-Willi syndrome is caused by genetic changes on an „unstable” region of chromosome 15 that affects the regulation of gene expression, or how genes turn on and off. […] The genetic changes that cause Prader-Willi syndrome occur in a portion of the chromosome, referred to as the Prader-Willi critical region (PWCR), around the time of conception or during early fetal development. […] Although Prader-Willi syndrome is genetic, it usually is not inherited and generally develops due to deletions or partial deletions on chromosome 15. […] A majority of PWS cases result from a deletion in one region of the father’s chromosome 15 that leads to a loss of function of several genes. […] The corresponding mother’s genes on chromosome 15 are always inactive and thus cannot make up for the deletion on the father’s chromosome 15.

• #6 What is Prader-Willi Syndrome

  https://www.fpwr.org/what-is-prader-willi-syndrome

  PWS is caused by a lack of active genetic material in a particular region of chromosome 15 (15q11-q13). […] The genetic defect causing the inactivity of chromosome 15 from the father (paternal chromosome 15) can occur in one of three ways: […] Most often, part of the chromosome 15 that was inherited from the persons father is missing, or deleted, in this critical region. This small deletion occurs in approximately 60% of cases and usually is not detectable with routine genetic analysis such as amniocentesis. […] Another 35-40% of cases occur when an individual inherits two chromosome 15s from their mother and none from their father. This scenario is termed maternal uniparental disomy (UPD). […] Finally, in a very small percentage of cases (1-3%), a small mutation in the Prader-Willi region causes the paternal chromosome 15 genetic material (although present) to be inactive.

• #7 Prader-Willi syndrome | Genetics in Medicine

  https://www.nature.com/articles/gim0b013e31822bead0

  Prader-Willi syndrome is due to absence of paternally expressed imprinted genes at 15q11.2-q13 through paternal deletion of this region (6575% of individuals), maternal uniparental disomy 15 (2030%), or an imprinting defect (13%). […] The absence of expression of one or more of the paternally inherited genes must contribute to the phenotype of PWS. This lack of expression occurs by three primary mechanisms: (i) deletion of a 56 Mb region from the paternally contributed chromosome 15 (found in 6575% of affected individuals); (ii) maternal uniparental disomy (UPD) 15 (found in 2030%); and (iii) a defect in the genomic region that controls the imprinting process, a so-called imprinting defect (ID; 13%). […] The genomic and epigenetic changes causing PWS all lead to a loss of expression of the normally paternally expressed genes on chromosome 15q11.2-q13. Absence of the paternally inherited copy of these genes, or failure to express them, causes total absence of expression for those genes in the affected individual because the maternal contribution for these genes has been programmed by epigenetic factors to be silenced.

• #8 Prader-Willi Syndrome: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/947954-overview

  Prader-Willi syndrome (PWS) is a disorder caused by a deletion or disruption of genes in the proximal arm of chromosome 15 or by maternal disomy in the proximal arm of chromosome 15. […] Prader-Willi syndrome results from the loss of imprinted genomic material within the paternal 15q11.2-13 locus. […] Approximately 70% of Prader-Willi syndrome cases arise from deletion of band 15q11-13 on chromosome 15. Maternal uniparental disomy caused by chromosomal nondisjunction accounts for 28% of Prader-Willi syndrome cases. […] Less than 1% of patients have mutations isolated to the imprinting center, which carries a risk of recurrence. […] Prader-Willi syndrome is caused by the loss of the paternal copy in the proximal arm of chromosome 15 in the region of 15p11-13.

• #9 What causes Prader-Willi syndrome (PWS)? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  http://www.nichd.nih.gov/health/topics/prader-willi/conditioninfo/causes

  In around one-fourth of PWS cases, the child has two copies of chromosome 15 from the mother and none from the father. […] Because genes located in the PWCR are normally inactive in the chromosome that comes from the mother, the child’s lack of active genes in this region leads to PWS. […] In a small percentage of PWS cases, the chromosome 15 inherited from the father is imprinted in the same way as the mother’s. […] This can be caused by a small deletion in a region of the father’s chromosome that controls the imprinting process, called the imprinting center. […] In these cases, both of the child’s copies of chromosome 15 have inactive PWCRs, leading to Prader-Willi syndrome.

• #10 Prader-Willi Syndrome: Symptoms & Causes

  https://my.clevelandclinic.org/health/diseases/21016-prader-willi-syndrome

  Maternal uniparental disomy: About 25% of PWS cases happen when a child inherits two maternal copies of chromosome 15 instead of one from each biological parent. This means that both copies of chromosome 15 don’t work because they’re inactive. […] Translocation: Less than 1% of all cases occur when a piece of chromosome 15 relocates itself to another chromosome. This makes the genes that the chromosome produces work ineffectively since they’re not where they’re supposed to be. […] A change to chromosome 15 limits its ability to create snoRNAs or they don’t receive the instructions they need to complete their jobs correctly.

• #11

  https://link.springer.com/article/10.1007/s40618-015-0312-9

  PWS individuals with the larger Type I deletion have been reported to be more prone to obsessive compulsion and self-injury (skin picking) in addition to visual processing deficits and lower measures of academic performance than those PWS individuals with the smaller Type II deletion having the four genes intact between proximal breakpoints BP1 and BP2. […] The second most frequent genetic finding in PWS is due to an error in meiosis, most common when two maternal chromosome 15 s are contributed in the egg and fertilized by a normal sperm. […] Most individuals with PWS are due to sporadic causes but in some families the defective error is from an epimutation or incomplete processing of the imprint in germ cell meiosis from the father or from a microdeletion of the DNA imprinting center.

• #12 What causes Prader-Willi syndrome (PWS)? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  http://www.nichd.nih.gov/health/topics/prader-willi/conditioninfo/causes

  In around one-fourth of PWS cases, the child has two copies of chromosome 15 from the mother and none from the father. […] Because genes located in the PWCR are normally inactive in the chromosome that comes from the mother, the child’s lack of active genes in this region leads to PWS. […] In a small percentage of PWS cases, the chromosome 15 inherited from the father is imprinted in the same way as the mother’s. […] This can be caused by a small deletion in a region of the father’s chromosome that controls the imprinting process, called the imprinting center. […] In these cases, both of the child’s copies of chromosome 15 have inactive PWCRs, leading to Prader-Willi syndrome.

• #13 Causes of Prader-Willi Syndrome (PWS)Envelope icon

  https://praderwillinews.com/causes-of-prader-willi-syndrome-pws/

  In less than 5% of people with the disease, the PWS locus of the father’s chromosome 15 is present. However, the genes are not functioning. This is because the PSW locus is silenced in the same way as the mother’s. […] In very rare cases, PWS may be the result of translocation in the PWS locus. Here, a portion of a chromosome breaks off and reattaches to a different chromosome. This results in the shifting of genetic material that leads to altered chromosome pairing and affects the normal regulation of genes.

• #14 What Is Prader-Willi Syndrome? Symptoms, Causes, Diagnosis, Treatment, and Prevention

  https://www.everydayhealth.com/prader-willi-syndrome/guide/

  A very small percentage of cases happen from an imprinting problem. Imprinting means that the ability of the gene to be turned on depends on which parent it came from. In this case, the genes on chromosome 15 from the father are there, but they’re „turned off” or silenced. […] The missing or inactive genes lead to the symptoms of Prader-Willi syndrome.

• #15 Prader–Willi syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Prader%E2%80%93Willi_syndrome

  Prader-Willi syndrome (PWS) is a rare genetic disorder caused by a loss of function of specific genes on chromosome 15. […] About 74% of cases occur when part of the father’s chromosome 15 is deleted. […] In another 25% of cases, the affected person has two copies of the maternal chromosome 15 from the mother and lacks the paternal copy. […] PWS is not generally inherited, but rather the genetic changes happen during the formation of the egg, sperm, or in early development. […] The risk to the sibling of an affected child of having PWS depends on the genetic mechanism that caused the disorder. […] The PW genes are the SNRPN and NDN genes, along with clusters of snoRNAs: SNORD64, SNORD107, SNORD108 and two copies of SNORD109, 29 copies of SNORD116 (HBII-85) and 48 copies of SNORD115 (HBII-52). […] Studies of human and mouse model systems have shown deletion of the 29 copies of the C/D box snoRNA SNORD116 (HBII-85) to be the primary cause of PWS.

• #16 Prader–Willi syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Prader%E2%80%93Willi_syndrome

  Prader-Willi syndrome (PWS) is a rare genetic disorder caused by a loss of function of specific genes on chromosome 15. […] About 74% of cases occur when part of the father’s chromosome 15 is deleted. […] In another 25% of cases, the affected person has two copies of the maternal chromosome 15 from the mother and lacks the paternal copy. […] PWS is not generally inherited, but rather the genetic changes happen during the formation of the egg, sperm, or in early development. […] The risk to the sibling of an affected child of having PWS depends on the genetic mechanism that caused the disorder. […] The PW genes are the SNRPN and NDN genes, along with clusters of snoRNAs: SNORD64, SNORD107, SNORD108 and two copies of SNORD109, 29 copies of SNORD116 (HBII-85) and 48 copies of SNORD115 (HBII-52). […] Studies of human and mouse model systems have shown deletion of the 29 copies of the C/D box snoRNA SNORD116 (HBII-85) to be the primary cause of PWS.

• #17 Prader-Willi syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/prader-willi-syndrome/

  Studies suggest that the loss of a particular group of snoRNA genes, known as the SNORD116 cluster, may play a major role in causing the signs and symptoms of Prader-Willi syndrome. […] In some people with Prader-Willi syndrome, the loss of a gene called OCA2 is associated with unusually fair skin and light-colored hair. […] Most cases of Prader-Willi syndrome are not inherited, particularly those caused by a deletion in the paternal chromosome 15 or by maternal uniparental disomy. […] Rarely, a genetic change responsible for Prader-Willi syndrome can be inherited.

• #18 Prader-Willi syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/prader-willi-syndrome/

  Studies suggest that the loss of a particular group of snoRNA genes, known as the SNORD116 cluster, may play a major role in causing the signs and symptoms of Prader-Willi syndrome. […] In some people with Prader-Willi syndrome, the loss of a gene called OCA2 is associated with unusually fair skin and light-colored hair. […] Most cases of Prader-Willi syndrome are not inherited, particularly those caused by a deletion in the paternal chromosome 15 or by maternal uniparental disomy. […] Rarely, a genetic change responsible for Prader-Willi syndrome can be inherited.

• #19 Prader-Willi syndrome – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/symptoms-causes/syc-20355997

  Prader-Willi syndrome is a genetic condition that is caused by an error in one or more genes. Although it’s not known exactly what causes Prader-Willi syndrome, the problem lies in the genes in a region of chromosome 15. […] Prader-Willi syndrome occurs because certain paternal genes that should be expressed aren’t because: […] A missing or changed gene on chromosome 15 disrupts how a portion of the brain called the hypothalamus typically works. This part of the brain controls the release of hormones. A hypothalamus that isn’t working properly can affect hunger, growth, sexual development, body temperature, mood and sleep. […] In most cases, a random gene change that isn’t inherited causes Prader-Willi syndrome. Finding which gene change caused Prader-Willi syndrome can help with genetic counseling.

• #20 Prader Willi Syndrome (PWS) | Nationwide Children’s Hospital

  https://www.nationwidechildrens.org/conditions/prader-willi-syndrome

  Prader-Willi syndrome is caused by changes in one or more genes located on chromosome 15. In people who have PWS, the copy of the gene(s) that comes from the father is not functional. […] A deletion is the most common cause of PWS, accounting for approximately 70% of cases. […] This occurs for one of the following three reasons: A small portion of the father’s chromosome 15 is missing (called a deletion), The child has two copies of chromosome 15 from the mother and has no copies of chromosome 15 from the father (called uniparental disomy or UPD), The father’s copy of the gene is not turned on properly (called an imprinting disorder).

• #21

  https://www.nhs.uk/conditions/prader-willi-syndrome/

  Prader-Willi syndrome is caused by some missing genetic material in a group of genes on chromosome number 15. […] This leads to a number of problems and is thought to affect part of the brain called the hypothalamus, which produces hormones and regulates growth and appetite. […] This may explain some of the typical features of Prader-Willi syndrome, such as delayed growth and persistent hunger. […] The genetic cause happens purely by chance, and boys and girls of all ethnic backgrounds can be affected. […] It’s extremely rare for parents to have more than 1 child with Prader-Willi syndrome.

• #22 Prader-Willi Homes | What is Prader-Willi Syndrome

  https://www.pwho.com/what-is-prader-willi-syndrome/

  An individual can acquire symptoms similar to those manifested in PWS by trauma to the hypothalamus through tumor, injury, or damage. […] Chromosome 15 controls the hypothalamus, the part of the brain that regulates body temperature and water balance; controls appetite; and influences blood pressure, sexual behavior, aggression, fear and sleep. The current school of thought says that in individuals with Prader-Willi syndrome, the hypothalamus is not working properly and the functions it controls are therefore affected.

• #23 What Is Prader-Willi Syndrome? – Symptoms and Causes

  https://www.pwsausa.org/what-is-prader-willi-syndrome/

  Prader-Willi syndrome (PWS) is a variable and complex genetic disorder resulting from an abnormality on the 15th chromosome. It occurs in males and females equally and in all races. Prevalence estimates range from 1:15,000 to 1:25,000. […] Experts believe that PWS is a multistage disorder characterized by decreased fetal movement during pregnancy and low birth weight. As toddlers get older, they start gaining more weight. If we don’t limit their calories, this can lead to excessive eating (hyperphagia) and obesity. […] Abnormalities on chromosome 15 cause Prader-Willi Syndrome (PWS). This happens 3 different ways: Gene Deletion: In many cases, critical genes on a portion of the father’s chromosome 15 are missing. This is the most common cause. […] Uniparental Disomy: The child has two copies of chromosome 15 from the mother instead of one from each parent. […] Imprinting Mutation: In less than 3% of cases, there is an imprinting mutation on the father’s chromosome 15. The genetic material is there but remains inactive.

• #24 Prader-Willi syndrome – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/3000311

  Prader-Willi syndrome (PWS; also known as Prader-Labhart-Willi syndrome) is a rare, complex, multisystem, neurologic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. […] The syndrome typically occurs due to one of three genetic mechanisms: paternal deletion of involved genes, maternal uniparental disomy, or imprinting center defects. […] PWS is the most common known genetic cause of life-threatening obesity in humans. […] Patients with PWS have a shorter life expectancy than the general population, which is mainly due to complications of hyperphagia and obesity.

• #25 Causes of death in Prader-Willi syndrome: lessons from 11 years’ experience of a national reference center | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1214-2

  Patients with PWS die prematurely due to a respiratory cause in most cases at all ages. […] Respiratory causes accounted for more than 50% of the deaths in patients with PWS in both children and adults. […] The literature has identified the complications of severe obesity as the main cause of death in adults, whereas death in children is mostly due to respiratory illness. […] Respiratory-related causes have been reported as the most common cause of death among children with PWS. […] Among the adults who died of respiratory causes, most presented restrictive ventilatory impairment, a known comorbidity in the PWS population. […] Several previous publications, however, have identified obesity-related cardiorespiratory pathologies as the leading causes of death among adults with PWS.

• #26 Prader-Willi syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/prader-willi-syndrome/

  Studies suggest that the loss of a particular group of snoRNA genes, known as the SNORD116 cluster, may play a major role in causing the signs and symptoms of Prader-Willi syndrome. […] In some people with Prader-Willi syndrome, the loss of a gene called OCA2 is associated with unusually fair skin and light-colored hair. […] Most cases of Prader-Willi syndrome are not inherited, particularly those caused by a deletion in the paternal chromosome 15 or by maternal uniparental disomy. […] Rarely, a genetic change responsible for Prader-Willi syndrome can be inherited.

• #27 What Causes Prader-Willi Syndrome?

  https://specialolympicsarizona.org/what-causes-prader-willi-syndrome/

  What Causes Prader-Willi Syndrome? Prader-Willi syndrome is a genetic disorder that is caused by genes on chromosome 15 losing function. […] The majority of Prader-Willi syndrome cases result from chromosomal deletions—nearly 70%. […] A smaller but still significant number of cases of Prader-Willi syndrome occur when a child inherits two chromosome 15s from the maternal genes instead of inheriting one paternal and one maternal. […] A very small number, less than 1%, of Prader-Willi cases occur when a chromosome relocates itself to another chromosome, a process called translocation. […] The majority of Prader-Willi syndrome cases are not inherited and instead are caused by a random genetic mutation that occurs during the formation of reproductive cells, eggs, or sperm, during early embryonic development. […] As mentioned, Prader-Willi syndrome is usually caused by a random genetic mutation and is very rarely inherited. […] Due to the spontaneous genetic mutation that causes Prader-Willi syndrome, it is not possible to prevent it.

• #28 Prader-Willi Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2005/0901/p827.html

  Prader-Willi syndrome (PWS), a genetic disorder that usually involves chromosome 15, is the most common form of obesity caused by a genetic syndrome. […] The specific gene that is expressed from a pair is determined by the sex of the parent transmitting it, a process called imprinting. The genes associated with PWS normally are expressed only from a region of chromosome 15 inherited from the father (PWS critical region). The genes inherited from the mother normally are inactivated. Therefore, children affected with PWS have a deletion or disruption of the chromosome inherited from the father or have inherited two copies of this chromosomal region from the mother. The latter situation is called maternal uniparental disomy. […] Genetic counseling often is helpful for parents of a child affected with PWS who are contemplating another pregnancy. The risk of recurrence varies widely (zero to 50 percent) depending on the underlying genetic origin and can be determined based on the results of genetic testing. Other family members may be at risk for having a child with PWS and may benefit from genetic counseling.

• #29 Prader-Willi Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2005/0901/p827.html

  Prader-Willi syndrome (PWS), a genetic disorder that usually involves chromosome 15, is the most common form of obesity caused by a genetic syndrome. […] The specific gene that is expressed from a pair is determined by the sex of the parent transmitting it, a process called imprinting. The genes associated with PWS normally are expressed only from a region of chromosome 15 inherited from the father (PWS critical region). The genes inherited from the mother normally are inactivated. Therefore, children affected with PWS have a deletion or disruption of the chromosome inherited from the father or have inherited two copies of this chromosomal region from the mother. The latter situation is called maternal uniparental disomy. […] Genetic counseling often is helpful for parents of a child affected with PWS who are contemplating another pregnancy. The risk of recurrence varies widely (zero to 50 percent) depending on the underlying genetic origin and can be determined based on the results of genetic testing. Other family members may be at risk for having a child with PWS and may benefit from genetic counseling.

• #30 Prader-Willi Syndrome – Brain Foundation

  https://brainfoundation.org.au/disorders/prader-willi-syndrome/

  Most cases of PWS are attributed to a spontaneous genetic error that occurs at or near the time of conception for unknown reasons. […] In 99% of cases it is not inherited. […] In a very small percentage of cases (2%), a genetic mutation that does not affect the parent is passed on to the child, and in these families more than one child may be affected. […] A PWS-like disorder can also be acquired after birth if the hypothalamic portion of the brain is damaged through injury or surgery.

• #31 Prader-Willi Homes | What is Prader-Willi Syndrome

  https://www.pwho.com/what-is-prader-willi-syndrome/

  An individual can acquire symptoms similar to those manifested in PWS by trauma to the hypothalamus through tumor, injury, or damage. […] Chromosome 15 controls the hypothalamus, the part of the brain that regulates body temperature and water balance; controls appetite; and influences blood pressure, sexual behavior, aggression, fear and sleep. The current school of thought says that in individuals with Prader-Willi syndrome, the hypothalamus is not working properly and the functions it controls are therefore affected.

• #32 Prader-Willi syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/prader-willi-syndrome/

  Prader-Willi syndrome is caused by the loss of function of genes in a particular region of chromosome 15. […] Most cases of Prader-Willi syndrome (about 70 percent) occur when a segment of the paternal chromosome 15 is deleted in each cell. […] In another 25 percent of cases, a person with Prader-Willi syndrome has two copies of chromosome 15 inherited from his or her mother (maternal copies) instead of one copy from each parent. […] Rarely, Prader-Willi syndrome can also be caused by a chromosomal rearrangement called a translocation, or by a genetic alteration or other change that abnormally turns off (inactivates) genes on the paternal chromosome 15. […] It appears likely that the characteristic features of Prader-Willi syndrome result from the loss of function of several genes on chromosome 15.

• #33 What Causes Prader-Willi Syndrome?

  https://specialolympicsarizona.org/what-causes-prader-willi-syndrome/

  What Causes Prader-Willi Syndrome? Prader-Willi syndrome is a genetic disorder that is caused by genes on chromosome 15 losing function. […] The majority of Prader-Willi syndrome cases result from chromosomal deletions—nearly 70%. […] A smaller but still significant number of cases of Prader-Willi syndrome occur when a child inherits two chromosome 15s from the maternal genes instead of inheriting one paternal and one maternal. […] A very small number, less than 1%, of Prader-Willi cases occur when a chromosome relocates itself to another chromosome, a process called translocation. […] The majority of Prader-Willi syndrome cases are not inherited and instead are caused by a random genetic mutation that occurs during the formation of reproductive cells, eggs, or sperm, during early embryonic development. […] As mentioned, Prader-Willi syndrome is usually caused by a random genetic mutation and is very rarely inherited. […] Due to the spontaneous genetic mutation that causes Prader-Willi syndrome, it is not possible to prevent it.

• #34 Prader-Willi Syndrome: The Disease that Opened up Epigenomic-Based Preemptive Medicine

  https://www.mdpi.com/2079-9721/4/1/15

  Furthermore, a recent study using induced pluripotent stem cells derived from the PWS patients revealed up-regulation of maternally expressed genes in the imprinted DLK1-DIO3 locus on chromosome 14 due to deficiency of the paternal allele of IPW, a long noncoding RNA at the 15q11–q13 locus that acts as a regulator of the DLK1-DIO3 region, and this indicates that a subset of PWS phenotypes may arise from dysregulation of an imprinted locus distinct from the PWS critical region of 15q11–q13.

• #35 Prader-Willi Syndrome: The Disease that Opened up Epigenomic-Based Preemptive Medicine

  https://www.mdpi.com/2079-9721/4/1/15

  Furthermore, a recent study using induced pluripotent stem cells derived from the PWS patients revealed up-regulation of maternally expressed genes in the imprinted DLK1-DIO3 locus on chromosome 14 due to deficiency of the paternal allele of IPW, a long noncoding RNA at the 15q11–q13 locus that acts as a regulator of the DLK1-DIO3 region, and this indicates that a subset of PWS phenotypes may arise from dysregulation of an imprinted locus distinct from the PWS critical region of 15q11–q13.

• #36

  https://link.springer.com/article/10.1007/s40618-015-0312-9

  PWS individuals with the larger Type I deletion have been reported to be more prone to obsessive compulsion and self-injury (skin picking) in addition to visual processing deficits and lower measures of academic performance than those PWS individuals with the smaller Type II deletion having the four genes intact between proximal breakpoints BP1 and BP2. […] The second most frequent genetic finding in PWS is due to an error in meiosis, most common when two maternal chromosome 15 s are contributed in the egg and fertilized by a normal sperm. […] Most individuals with PWS are due to sporadic causes but in some families the defective error is from an epimutation or incomplete processing of the imprint in germ cell meiosis from the father or from a microdeletion of the DNA imprinting center.

• #37 Prader-Willi syndrome – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/symptoms-causes/syc-20355997

  Prader-Willi syndrome is a genetic condition that is caused by an error in one or more genes. Although it’s not known exactly what causes Prader-Willi syndrome, the problem lies in the genes in a region of chromosome 15. […] Prader-Willi syndrome occurs because certain paternal genes that should be expressed aren’t because: […] A missing or changed gene on chromosome 15 disrupts how a portion of the brain called the hypothalamus typically works. This part of the brain controls the release of hormones. A hypothalamus that isn’t working properly can affect hunger, growth, sexual development, body temperature, mood and sleep. […] In most cases, a random gene change that isn’t inherited causes Prader-Willi syndrome. Finding which gene change caused Prader-Willi syndrome can help with genetic counseling.

• #38 Prader-Willi syndrome | Chask

  https://www.chask.org/prader-willi-syndrome

  Prader-Willi Syndrome (PWS) involves a disorder of chromosome 15. The disorder affects approximately one out of every twelve to fifteen thousand people from both sexes and all races. […] While the cause of PWS is complex, the disorder is the most common known genetic cause of life-threatening obesity in children. […] The cause of PWS is genetic, from a loss of genes that are usually contributed by the child’s father, which remain unidentified at this time. What is known is that PWS occurs from three main genetic errors. Approximately seventy-percent of people with the disorder have a non-inherited deletion in the paternally-contributed chromosome 15. Around twenty-five percent have maternal uniparental disomy (UPD), or two maternal 15 and no paternal chromosome 15. Two-to-five percent of people with PWS have an error in the, imprinting, process, which renders the paternal contribution non-functional. […] Genetic testing is the preferred means of diagnosing PWS. DNA methylation analysis can confirm a diagnosis of the disorder. FISH, and DNA techniques may identify the particular gene cause and associated risk of recurrence.

• #39 Prader-Willi Syndrome: Life Expectancy, Prevention, and More

  https://www.healthline.com/health/prader-willi-syndrome-life-expectancy

  Prader-Willi syndrome (PWS) is a rare genetic disorder that develops due to the deletion of chromosome 15. […] While PWS on its own does not cause early death, complications from overeating and obesity may shorten an individual’s lifespan. […] According to the National Health Service (NHS) in the United Kingdom, the risk of early death may increase if a person eats excessively (hyperphagia), gains weight, and develops health conditions related to obesity. […] One of the biggest risk factors for early death is obesity. […] Low levels of human growth hormone or delayed treatment with human growth hormone may also increase the risk of early death. […] Early diagnosis, understanding of complications, and continued treatment may help prevent early death for people with PWS. […] More specifically, compulsive eating is a significant predictor of early death. […] Treating low growth hormone issues may also help. […] PWS itself does not shorten a person’s life expectancy. Early diagnosis and appropriate treatment may prevent associated complications from becoming life threatening.

• #40 Prader–Willi syndrome | European Journal of Human Genetics

  https://www.nature.com/articles/ejhg2008165

  Prader-Willi syndrome (PWS) is a highly variable genetic disorder affecting multiple body systems whose most consistent major manifestations include hypotonia with poor suck and poor weight gain in infancy; mild mental retardation, hypogonadism, growth hormone insufficiency causing short stature for the family, early childhood-onset hyperphagia and obesity, characteristic appearance, and behavioral and sometimes psychiatric disturbance. […] PWS is an example of a genetic condition involving genomic imprinting. It can occur by three main mechanisms, which lead to absence of expression of paternally inherited genes in the 15q11.2q13 region: paternal microdeletion, maternal uniparental disomy, and imprinting defect. […] Major characteristics include infantile lethargy and hypotonia causing poor feeding and failure to thrive, developmental and intellectual disability, hypogonadism (small external genitalia and pubertal insufficiency), hyperphagia leading to morbid obesity if uncontrolled, short stature, characteristic facial appearance and body habitus, and a typical behavioral phenotype that includes temper tantrums and compulsive traits.

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