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Schaaf‐Yang syndrome overview: Report of 78 individuals

Schaaf‐Yang Syndrome (SYS) is a genetic disorder caused by truncating pathogenic variants in the paternal allele of the maternally imprinted, paternally expressed gene MAGEL2, located in the Prader‐Willi critical region 15q11‐15q13. SYS is a neurodevelopmental disorder that has clinical overlap with...

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Autores principales: McCarthy, John, Lupo, Philip J., Kovar, Erin, Rech, Megan, Bostwick, Bret, Scott, Daryl, Kraft, Katerina, Roscioli, Tony, Charrow, Joel, Schrier Vergano, Samantha A., Lose, Edward, Smiegel, Robert, Lacassie, Yves, Schaaf, Christian P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585857/
https://www.ncbi.nlm.nih.gov/pubmed/30302899
http://dx.doi.org/10.1002/ajmg.a.40650
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author McCarthy, John
Lupo, Philip J.
Kovar, Erin
Rech, Megan
Bostwick, Bret
Scott, Daryl
Kraft, Katerina
Roscioli, Tony
Charrow, Joel
Schrier Vergano, Samantha A.
Lose, Edward
Smiegel, Robert
Lacassie, Yves
Schaaf, Christian P.
author_facet McCarthy, John
Lupo, Philip J.
Kovar, Erin
Rech, Megan
Bostwick, Bret
Scott, Daryl
Kraft, Katerina
Roscioli, Tony
Charrow, Joel
Schrier Vergano, Samantha A.
Lose, Edward
Smiegel, Robert
Lacassie, Yves
Schaaf, Christian P.
author_sort McCarthy, John
collection PubMed
description Schaaf‐Yang Syndrome (SYS) is a genetic disorder caused by truncating pathogenic variants in the paternal allele of the maternally imprinted, paternally expressed gene MAGEL2, located in the Prader‐Willi critical region 15q11‐15q13. SYS is a neurodevelopmental disorder that has clinical overlap with Prader‐Willi Syndrome in the initial stages of life but becomes increasingly distinct throughout childhood and adolescence. Here, we describe the phenotype of an international cohort of 78 patients with nonsense or frameshift mutations in MAGEL2. This cohort includes 43 individuals that have been reported previously, as well as 35 newly identified individuals with confirmed pathogenic genetic variants. We emphasize that intellectual disability/developmental delay, autism spectrum disorder, neonatal hypotonia, infantile feeding problems, and distal joint contractures are the most consistently shared features of patients with SYS. Our results also indicate that there is a marked prevalence of infantile respiratory distress, gastroesophageal reflux, chronic constipation, skeletal abnormalities, sleep apnea, and temperature instability. While there are many shared features, patients with SYS are characterized by a wide phenotypic spectrum, including a variable degree of intellectual disability, language development, and motor milestones. Our results indicate that the variation in phenotypic severity may depend on the specific location of the truncating mutation, suggestive of a genotype–phenotype association. This evidence may be useful in both prenatal and pediatric genetic counseling.
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spelling pubmed-65858572019-06-27 Schaaf‐Yang syndrome overview: Report of 78 individuals McCarthy, John Lupo, Philip J. Kovar, Erin Rech, Megan Bostwick, Bret Scott, Daryl Kraft, Katerina Roscioli, Tony Charrow, Joel Schrier Vergano, Samantha A. Lose, Edward Smiegel, Robert Lacassie, Yves Schaaf, Christian P. Am J Med Genet A Research Articles Schaaf‐Yang Syndrome (SYS) is a genetic disorder caused by truncating pathogenic variants in the paternal allele of the maternally imprinted, paternally expressed gene MAGEL2, located in the Prader‐Willi critical region 15q11‐15q13. SYS is a neurodevelopmental disorder that has clinical overlap with Prader‐Willi Syndrome in the initial stages of life but becomes increasingly distinct throughout childhood and adolescence. Here, we describe the phenotype of an international cohort of 78 patients with nonsense or frameshift mutations in MAGEL2. This cohort includes 43 individuals that have been reported previously, as well as 35 newly identified individuals with confirmed pathogenic genetic variants. We emphasize that intellectual disability/developmental delay, autism spectrum disorder, neonatal hypotonia, infantile feeding problems, and distal joint contractures are the most consistently shared features of patients with SYS. Our results also indicate that there is a marked prevalence of infantile respiratory distress, gastroesophageal reflux, chronic constipation, skeletal abnormalities, sleep apnea, and temperature instability. While there are many shared features, patients with SYS are characterized by a wide phenotypic spectrum, including a variable degree of intellectual disability, language development, and motor milestones. Our results indicate that the variation in phenotypic severity may depend on the specific location of the truncating mutation, suggestive of a genotype–phenotype association. This evidence may be useful in both prenatal and pediatric genetic counseling. John Wiley & Sons, Inc. 2018-10-10 2018-12 /pmc/articles/PMC6585857/ /pubmed/30302899 http://dx.doi.org/10.1002/ajmg.a.40650 Text en © 2018 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
McCarthy, John
Lupo, Philip J.
Kovar, Erin
Rech, Megan
Bostwick, Bret
Scott, Daryl
Kraft, Katerina
Roscioli, Tony
Charrow, Joel
Schrier Vergano, Samantha A.
Lose, Edward
Smiegel, Robert
Lacassie, Yves
Schaaf, Christian P.
Schaaf‐Yang syndrome overview: Report of 78 individuals
title Schaaf‐Yang syndrome overview: Report of 78 individuals
title_full Schaaf‐Yang syndrome overview: Report of 78 individuals
title_fullStr Schaaf‐Yang syndrome overview: Report of 78 individuals
title_full_unstemmed Schaaf‐Yang syndrome overview: Report of 78 individuals
title_short Schaaf‐Yang syndrome overview: Report of 78 individuals
title_sort schaaf‐yang syndrome overview: report of 78 individuals
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585857/
https://www.ncbi.nlm.nih.gov/pubmed/30302899
http://dx.doi.org/10.1002/ajmg.a.40650
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