A case of YY1-associated syndromic learning disability or Gabriele-de Vries syndrome with myasthenia gravis
A case of YY1-associated syndromic learning disability or Gabriele-de Vries syndrome with myasthenia gravis
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DOI：
10.1002/ajmg.a.40626
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发表时间：
2018-12-01
影响因子：
2
通讯作者：
Dhamija, Radhika
中科院分区：
文献类型：
--
作者：
Morales-Rosado, Joel A.;Kaiwar, Charu;Dhamija, Radhika
外显子组测序越来越多地用于评估智力残疾患者。YY1是一种普遍分布的转录因子，属于锌指蛋白的GLIKruppel类，最近在23例加布里埃尔-德弗里斯综合征患者中被认为是致病基因。我们报告了一个具有相似特征的新病例，并在YY1基因的一个区域中发现了一个新的变体，这在以前没有报道过。一名25岁女性，被诊断为自身免疫性重症肌无力、面部畸形和学习障碍。先天性肌无力综合征的染色体微阵列和基因面板检测均为阴性。全外显子组测序（WES）结果显示，在YY1基因c.860_864delTTAAAA, p.Ile287Argfs*3中发现了一种可能致病的新杂合截断变异。Ile287残基是跨物种保守的，位于该蛋白的转录抑制结构域。这种变异是新颖的，位于以前没有报道的变异发生的蛋白质区域。本病例的表型特征与报道的患者的表型特征非常吻合。自身免疫性重症肌无力在这些患者中尚未报道，可能构成该表型谱的扩展，或者更可能是第二种不相关的诊断。
Exome sequencing is being used increasingly to evaluate patients with intellectual disability. YY1 is a ubiquitously distributed transcription factor belonging to the GLIKruppel class of zinc finger proteins recently recognized as the causative gene in 23 patients for the Gabriele-de Vries syndrome. We report a new case with similar features and a novel variant in YY1, in a region of the gene, which has not previously been reported. A 25 year old female was referred to clinical genetics with a diagnosis of autoimmune myasthenia gravis, facial dysmorphism and learning disability. Chromosomal microarray and gene panel test for congenital myasthenic syndrome was negative. Whole exome sequencing (WES) revealed a presumed pathogenic de novo novel, heterozygous, truncating variant in the YY1 gene, c.860_864delTTAAAA, p.Ile287Argfs*3. The Ile287 residue is conserved across species and is situated in the transcription repressor domain of the protein. This variant is novel and lies in a domain of the protein where no previously reported variants occur. The phenotypic features of our case closely match those of the reported patients. Autoimmune myasthenia gravis has not been reported in these patients and may constitute an expansion of this phenotypic spectrum or perhaps more likely a second unrelated diagnosis.