Mutations in SCARF2 Are Responsible for Van Den Ende-Gupta Syndrome
Mutations in SCARF2 Are Responsible for Van Den Ende-Gupta Syndrome
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DOI：
10.1016/j.ajhg.2010.09.005
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发表时间：
2010-10-08
影响因子：
9.8
通讯作者：
Jerome-Majewska, Loydie A.
中科院分区：
文献类型：
--
作者：
Anastasio, Natascia;Ben-Omran, Tawfeg;Jerome-Majewska, Loydie A.
货车Den Ende-Gupta综合征（VDEGS）是一种极为罕见的常染色体隐性遗传疾病，其特征为独特的颅面特征，包括小睑裂、颧骨和/或上颌骨发育不全、窄鼻和喙状鼻以及外翻的下唇。我们目前的分子数据的四个VDEGS患者来自三个近亲卡塔尔家庭属于同一高度近亲繁殖的贝都因部落。患者进行基因分型与SNP微阵列，和2 - 4 Mb纯合区域被发现在染色体22 q11上的区域重叠的DiGeorge关键区域。该区域包含44个基因，包括SCARF 2，该基因在发育期间在与上述症状相关的许多小鼠组织中表达。桑格测序鉴定了两个密切相关的患者的外显子4中的错义改变，c 773 G>A（p C258 Y）和外显子8中的2 bp缺失，c 1328_1329 delTG（p.V4431DfsX83），在两个不相关的个体中，与候选基因方法平行，使用完整的外显子组测序来确认SCARF 2是负责VDEGS的基因。SCARF 2在其细胞外结构域中含有推定的表皮生长因子样结构域，在其细胞内结构域中沿着许多带正电荷的残基，表明它可能参与细胞内信号传导。然而，SCAM：2的功能尚未得到表征，这项研究报告表型效应可能与清道夫受体F家族基因的缺陷有关
Van Den Ende-Gupta syndrome (VDEGS) is an extremely rare autosomal-recessive disorder characterized by distinctive craniofacial features, which include blepharophimosis, malar and/or maxillary hypoplasia, a narrow and beaked nose, and an everted lower hp Other features are arachnodactyly, camptodactyly, peculiar skeletal abnormalities, and normal development and intelligence. We present molecular data on four VDEGS patients from three consanguineous Qatari families belonging to the same highly inbred Bedouin tribe. The patients were genotyped with SNP microarrays, and a 2 4 Mb homozygous region was found on chromosome 22q11 in an area overlapping the DiGeorge critical region. This region contained 44 genes, including SCARF2, a gene that is expressed during development in a number of mouse tissues relevant to the symptoms described above Sanger sequencing identified a missense change, c 773G>A (p C258Y), in exon 4 in the two closely related patients and a 2 bp deletion in exon 8, c.1328_1329delTG (p.V4431DfsX83), in two unrelated individuals In parallel with the candidate gene approach, complete exome sequencing was used to confirm that SCARF2 was the gene responsible for VDEGS. SCARF2 contains putative epidermal growth factor-like domains in its extracellular domain, along with a number of positively charged residues in its intracellular domain, indicating that it may be involved in intracellular signaling However, the function of SCAM:2 has not been characterized, and this study reports that phenotypic effects can be associated with defects in the scavenger receptor F family of genes