Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome
Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome
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DOI：
10.1007/s00439-014-1456-y
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发表时间：
2014-09-01
期刊：
影响因子：
5.3
通讯作者：
Hennekam, Raoul C.
中科院分区：
文献类型：
--
作者：
Alders, Marielle;Al-Gazali, Lihadh;Hennekam, Raoul C.
Hennekam淋巴管扩张-水肿综合征是一种遗传异质性疾病。它可能是由CCBE 1突变引起的，在大约25%的病例中发现了这种突变。我们使用纯合性定位和全外显子组测序的原始HS家庭与多个受影响的个人，其中没有检测到CCBE 1突变，并确定了一个纯合突变的FAT 4基因。随后对24例CCBE 1突变阴性的Hennekam综合征患者进行了FAT 4靶向突变分析，在另外4个家族中发现了纯合或复合杂合突变。FAT 4突变以前与货车Maldergem综合征有关。货车Maldergem综合征和Hennekam综合征患者之间的详细临床比较表明，在表型上，特别是在面部外观上，存在大量重叠。我们的结论是Hennekam综合征可能是由FAT 4突变引起的，与货车Maldergem综合征是等位基因。
The Hennekam lymphangiectasia-lymphedema syndrome is a genetically heterogeneous disorder. It can be caused by mutations in CCBE1 which are found in approximately 25 % of cases. We used homozygosity mapping and whole-exome sequencing in the original HS family with multiple affected individuals in whom no CCBE1 mutation had been detected, and identified a homozygous mutation in the FAT4 gene. Subsequent targeted mutation analysis of FAT4 in a cohort of 24 CCBE1 mutation-negative Hennekam syndrome patients identified homozygous or compound heterozygous mutations in four additional families. Mutations in FAT4 have been previously associated with Van Maldergem syndrome. Detailed clinical comparison between van Maldergem syndrome and Hennekam syndrome patients shows that there is a substantial overlap in phenotype, especially in facial appearance. We conclude that Hennekam syndrome can be caused by mutations in FAT4 and be allelic to Van Maldergem syndrome.