Familial Gordon Syndrome Associated with a PIEZO2 Mutation
Familial Gordon Syndrome Associated with a PIEZO2 Mutation
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DOI：
10.1002/ajmg.a.37997
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发表时间：
2017-01-01
影响因子：
2
通讯作者：
Horn, Denise
中科院分区：
文献类型：
--
作者：
Alisch, Franz;Weichert, Alexander;Horn, Denise
戈登综合征或远端关节弯曲3型是一种罕见的常染色体显性遗传疾病，其特征是上下肢挛缩。它与其他形式的远端关节弯曲的区别在于腭裂和身材矮小。最近，戈登综合征与压电型机械敏感离子通道组分2基因（PIEZO 2）的杂合突变有关。该基因的不同突变也导致远端关节弯曲症5型和马登沃克综合征。这种离子通道的功能障碍对关节、眼肌和骨骼发育产生多效性作用。在这里，我们提出了一个家庭的三个受影响的个人表现出多发性挛缩（掌指骨和指间关节以及肘，肩，膝，踝关节），马蹄内翻足，身材矮小，双悬雍垂/腭裂，和一个独特的面部表型，包括上睑下垂。此外，轻度智力残疾和精神发育迟缓也很明显。戈登综合征的多代表型谱存在于37岁的父亲，他4岁的儿子和一名男性新生儿中，在妊娠13周时的产前超声检查中已经看到了关节弯曲的典型体征。在所有受影响的家族成员中，我们通过桑格测序鉴定了PIEZO 2突变c.8057 G>A（p.Arg2686 His）。我们的分析表明，轻度延迟的精神发育和智力残疾可能是戈登综合征的表型谱的一部分。(C)2016 Wiley Periodicals，Inc.
Gordon syndrome or distal arthrogryposis type 3 is a rare autosomal dominant disorder characterized by contractures of upper and lower limbs. It is distinguishable from other forms of distal arthrogryposis by cleft palate and short stature. Recently, Gordon syndrome has been associated to heterozygous mutations in the piezo-type mechanosensitive ion channel component 2 gene (PIEZO2). Different mutations of this gene also cause distal arthrogryposis type 5 and Marden-Walker syndrome. Dysfunction of this ion channel provides pleiotropic effects on joints, ocular muscles, and bone development. Here, we present a family with three affected individuals exhibiting multiple contractures (metacarpo-phalangeal and interphalangeal joints as well as elbow, shoulder, knee, and ankle joints), clubfeet, short stature, bifid uvula/cleft palate, and a distinct facial phenotype including ptosis. In addition, mild intellectual disability and delay in psychomotor development are obvious. The multigenerational phenotypic spectrum of Gordon syndrome is present in the 37-year-old father, his 4-year-old son and a male neonate showing typical signs of arthrogryposis in the prenatal ultrasound examination already seen at 13 week of gestation. In all affected family members, we identified the PIEZO2 mutation c.8057G>A (p.Arg2686His) by Sanger sequencing. Our analysis indicated that mild delay in psychomotor development and intellectual disability could be part of the phenotypic spectrum of Gordon syndrome. (C) 2016 Wiley Periodicals, Inc.