TMCO1 Deficiency Causes Autosomal Recessive Cerebrofaciothoracic Dysplasia
TMCO1 Deficiency Causes Autosomal Recessive Cerebrofaciothoracic Dysplasia
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DOI：
10.1002/ajmg.a.36248
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发表时间：
2014-02-01
影响因子：
2
通讯作者：
Akarsu, Nurten Ayse
中科院分区：
文献类型：
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作者：
Alanay, Yasemin;Erguner, Bekir;Akarsu, Nurten Ayse
脑面胸发育不良（CFT） （OMIM #213980）是一种累及颅骨、面部和胸部的多发性先天性异常和智力残疾综合征。其特征性表现为新生儿大颅畸形、头短、各种CT/MRI表现包括胼胝体发育不全、膜隔增大、弥漫性灰质低密度、面部扁平、远端肥大、唇裂、腭裂、耳后旋低、颈部短以及多发肋和椎体异常。潜在的遗传缺陷仍然未知。利用纯合子图谱和全外显子组测序相结合，我们鉴定出了一个纯合子无义创始人突变p.a g87ter （c.259）C b> T)，在土耳其血统的5个家族中有4个家族的人跨膜和卷曲结构域蛋白1 （TMCO1）中存在。第5家族排除了染色体1q24上含有TMCO1的整个关键区域，CFT的特征性发现为CFT谱的遗传异质性提供了证据。另一个创始人TMCO1突变最近被报道导致一种独特的遗传状况，TMCO1缺陷综合征（omim# 614132）。tmco1缺陷综合征与CFT有许多共同特征。这项研究支持这样一个事实，即最初被认为是一种独特疾病的tmco1缺陷综合征，确实属于遗传异质性CFT发育不良谱系。(c) 2013 Wiley Periodicals, Inc.；
Cerebrofaciothoracic dysplasia (CFT) (OMIM #213980) is a multiple congenital anomaly and intellectual disability syndrome involving the cranium, face, and thorax. The characteristic features are cranial involvement with macrocrania at birth, brachycephaly, various CT/MRI findings including hypoplasia of corpus callosum, enlargement of septum pellicidum, and diffuse hypodensity of the grey matter, flat face, hypertelorism, cleft lip and cleft palate, low-set, posteriorly rotated ears, short neck, and multiple costal and vertebral anomalies. The underlying genetic defect remains unknown. Using combination of homozygosity mapping and whole-exome sequencing, we identified a homozygous nonsense founder mutation, p.Arg87Ter (c.259 C>T), in the human transmembrane and coiled-coil domains protein 1 (TMCO1) in four out of five families of Turkish origin. The entire critical region on chromosome 1q24 containing TMCO1 was excluded in the fifth family with characteristic findings of CFT providing evidence for genetic heterogeneity of CFT spectrum. Another founder TMCO1 mutation has recently been reported to cause a unique genetic condition, TMCO1-defect syndrome (OMIM #614132). TMCO1-defect syndrome shares many features with CFT. This study supports the fact that TMCO1-defect syndrome, initially thought to represent a distinct disorder, indeed belongs to the genetically heterogeneous CFT dysplasia spectrum. (c) 2013 Wiley Periodicals, Inc.