MASP1 Mutations in Patients with Facial, Umbilical, Coccygeal, and Auditory Findings of Carnevale, Malpuech, OSA, and Michels Syndromes
MASP1 Mutations in Patients with Facial, Umbilical, Coccygeal, and Auditory Findings of Carnevale, Malpuech, OSA, and Michels Syndromes
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DOI：
10.1016/j.ajhg.2010.09.018
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发表时间：
2010-11-12
影响因子：
9.8
通讯作者：
Tekin, Mustafa
中科院分区：
文献类型：
--
作者：
Sirmaci, Asli;Walsh, Tom;Tekin, Mustafa
常染色体隐性遗传的 Carnevale、Malpuech、Michels 和眼骨腹 (OSA) 综合征中可观察到独特的面部特征，包括距离过远、外眦赘皮、睑裂、上睑下垂、内眦赘皮、periumbil seal 缺陷和骨骼异常。迄今为止，导致这些综合征的一个或多个基因尚不清楚。我们报告了来自两个近亲土耳其人的三个个体具有这些综合征特征的家庭，包括面部畸形、脐周抑郁症、混合性听力损失、桡尺骨性联结和尾骨附器 纯合性图谱在两个家庭的染色体 3q27 上均产生自合区域 在一个家庭中，全外显子组测序显示出一种错义突变，MASP1 c 2059G>A (p G687R)，与表型共分离 在第二个家庭中，MASP1 的桑格测序揭示了一个无义突变 MASP1 c 870G>A (p W290X)，也与表型共分离 在 192 个土耳其对照或 1200 个其他各种血统的对照中均未发现突变 MASP1 编码甘露聚糖结合凝集素 senne 蛋白酶 1 这两个突变发生在 MASP1 同种型中，据报道，该同种型可处理 IGFBP 5，从而在胰岛素生长因子的可用性中发挥关键作用颅面和肌肉发育这些结果表明 MASP1 突变是人类畸形综合征的原因，并证明 MASP1 参与胚胎期的面部、脐带和耳朵发育
Distinctive facial features consisting of hypertelorism, telecanthus, blepharophimosis blepharoptosis, epicanthus inversus, periumbil seal defects, and skeletal anomalies are seen in autosomal recessive Carnevale, Malpuech, Michels, and oculo skeletal abdominal (OSA) syndromes The gene or genes responsible for these syndromes were heretofore unknown We report on three individuals from two consanguineous Turkish families with findings characteristic of these syndromes including facial dysmorphism periumbilical depression mixed hearing loss, radioulnar synostosis and coccygeal appendage Homozygosity mapping yielded an autozygous region on chromosome 3q27 in both families In one family, whole exome sequencing revealed a missense mutation, MASP1 c 2059G>A (p G687R) that cosegregated with the phenotype In the second family, Sanger sequencing of MASP1 revealed a nonsense mutation, MASP1 c 870G>A (p W290X) that also cosegregated with the phenotype Neither mutation was found in 192 Turkish controls or 1200 controls of various other ancestries MASP1 encodes mannan binding lectin senne protease 1 The two mutations occur in a MASP1 isoform that has been reported to process IGFBP 5 thereby playing a critical role in insulin growth factor availability during craniofacial and muscle development These results implicate mutations of MASP1 as the cause of a human malformation syndrome and demonstrate the involvement of MASP1 in facial, umbilical, and ear development during the embryonic period