Schaaf-Yang syndrome overview: Report of 78 individuals.
Schaaf-Yang syndrome overview: Report of 78 individuals.
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DOI：
10.1002/ajmg.a.40650
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Schaaf CP
中科院分区：
文献类型：
--
作者：
McCarthy J;Lupo PJ;Kovar E;Rech M;Bostwick B;Scott D;Kraft K;Roscioli T;Charrow J;Schrier Vergano SA;Lose E;Smiegel R;Lacassie Y;Schaaf CP
Schaaf-Yang 综合征 (SYS) 是一种遗传性疾病，由位于 Prader-Willi 关键区域 15q11-15q13 的母系印记、父系表达基因 MAGEL2 的父系等位基因截断致病性变异引起。 SYS 是一种神经发育障碍，在生命的最初阶段与普瑞德威利综合征有临床重叠，但在整个童年和青春期变得越来越明显。在这里，我们描述了 78 名 MAGEL2 无义或移码突变患者的国际队列的表型。该队列包括 43 名之前报道过的个体，以及 35 名新发现的具有已确认致病性遗传变异的个体。我们强调，智力障碍/发育迟缓、自闭症谱系障碍、新生儿肌张力低下、婴儿喂养问题和远端关节挛缩是 SYS 患者最一致的共同特征。我们的结果还表明，婴儿呼吸窘迫、胃食管反流、慢性便秘、骨骼异常、睡眠呼吸暂停和体温不稳定的患病率显着。虽然有许多共同特征，但 SYS 患者的表型谱广泛，包括不同程度的智力障碍、语言发育和运动里程碑。我们的结果表明，表型严重程度的变化可能取决于截短突变的具体位置，提示基因型-表型关联。该证据可能对产前和儿科遗传咨询有用。
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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影响因子：
1.9
作者：
Bayat, Allan;Bayat, Michael;Schaaf, Christian P.
通讯作者：
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作者：
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