Syndromic intellectual disability: A new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant
Syndromic intellectual disability: A new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant
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DOI：
10.1016/j.gene.2015.01.026
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发表时间：
2015-04-01
期刊：
影响因子：
3.5
通讯作者：
Seri, Marco
中科院分区：
文献类型：
--
作者：
Graziano, Claudio;Wischmeijer, Anita;Seri, Marco
通过全外显子组测序（WES）分析，在一个近亲家庭中，三名患者（两个兄弟姐妹和一个堂兄弟）表现为智力残疾、马凡样体型、颅面畸形、慢性腹泻和进行性脊柱后凸，已确定了致病变异。WES研究在患者中鉴定了纯合DDC变异，c.1123C>T，导致p.Arg375Cys错义替换。DDC突变导致隐性代谢紊乱（芳香族氨基酸脱羧酶，AADC，缺乏，OMIM #608643），其特征在于张力减退、眼球转动危象、过度出汗、温度不稳定、肌张力障碍、婴儿期严重神经功能障碍，以及脑脊髓液（CSF）中神经递质及其代谢物的特异性异常。在我们的家庭中，分析神经递质及其代谢产物在患者的CSF中显示出与AADC缺乏症兼容的模式，尽管临床体征与经典形式不同。我们的工作扩展了与DDC变体相关的表型谱，因此可以导致额外的新综合征，而没有典型的运动异常。(C)2015 Elsevier B.V.版权所有。
The causative variant in a consanguineous family in which the three patients (two siblings and a cousin) presented with intellectual disability, Marfanoid habitus, craniofacial dysmorphisms, chronic diarrhea and progressive kyphoscoliosis, has been identified through whole exome sequencing (WES) analysis. WES study identified a homozygous DDC variant in the patients, c.1123C>T, resulting in p.Arg375Cys missense substitution.Mutations in DDC cause a recessive metabolic disorder (aromatic amino acid decarboxylase, AADC, deficiency, OMIM #608643) characterized by hypotonia, oculogyric crises, excessive sweating, temperature instability, dystonia, severe neurologic dysfunction in infancy, and specific abnormalities of neurotransmitters and their metabolites in the cerebrospinal fluid (CSF). In our family, analysis of neurotransmitters and their metabolites in patient's CSF shows a pattern compatible with AADC deficiency, although the clinical signs are different from the classic form. Our work expands the phenotypic spectrum associated with DDC variants, which therefore can cause an additional novel syndrome without typical movement abnormalities. (C) 2015 Elsevier B.V. All rights reserved.