SALL1 Mutation Analysis in Townes-Brocks Syndrome: Twelve Novel Mutations and Expansion of the Phenotype
SALL1 Mutation Analysis in Townes-Brocks Syndrome: Twelve Novel Mutations and Expansion of the Phenotype
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DOI：
10.1002/humu.9362
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发表时间：
2005-09-01
期刊：
影响因子：
3.9
通讯作者：
Kohlhase, Juergen
中科院分区：
文献类型：
--
作者：
Botzenhart, Elke M.;Green, Andrew;Kohlhase, Juergen
汤斯-布罗克斯综合征是一种常染色体显性遗传性疾病，包括多个出生缺陷，包括肾脏、耳朵、肛门和四肢畸形。TBS已被证明是由SALL1基因突变引起的，SALL1是一种与果蝇发育调节因子SAL相关的人类基因。SALL1基因产物是一种锌指蛋白，被认为是一种转录因子。它包含四个高度保守、分布均匀的C2H2双锌指结构域。单个C2H2基序附着在第二个结构域上，在氨基末端SALL1包含一个C2HC基序。大多数导致TBS的突变都聚集在SALL1编码区的N端三分之一，并导致产生的截短蛋白只包含SALL1的C2H2结构域和N端转录抑制器域中的一个或不包含。在此之前已报道了23个SALL1突变，其中22个位于第二个双锌指编码区的外显子2，5‘。在此，我们报告了13个无关家系中与汤氏-布罗克斯综合征相关的12个新的SALL1突变。这些突变包括三个无义突变、三个短插入和六个短缺失。因此，SALL1突变的数量增加到35个。基因突变阳性患者中罕见的表型特征包括甲状腺功能减退、阴道发育不全伴子宫二裂、隐睾症、阴囊二裂但无阴囊下裂、单侧绒毛视网膜缺损伴视力丧失、胼胝体背侧发育不良和脐疝。(C)2005年Wiley-Liss，Inc.
Townes-Brocks syndrome is an autosomal dominantly inherited disorder, which comprises multiple birth defects including renal, ear, anal, and limb malformations. TBS has been shown to result from mutations in SALL1, a human gene related to the developmental regulator SAL of Drosophila melanogaster. The SALL1 gene product is a zinc finger protein thought to act as a transcription factor. It contains four highly conserved, evenly distributed C2H2 double zinc finger domains. A single C2H2 motif is attached to the second domain, and at the amino terminus SALL1 contains a C2HC motif. Most mutations causing TBS are clustered in the N-terminal third of the SALL1 coding region and result in the production of truncated proteins containing only one or none of the C2H2 domains and the N-terminal transcriptional repressor domain of SALL1. Twenty-three SALL1 mutations were reported prior to this work, 22 of which are located in exon 2, 5' of the second double zinc finger-encoding region. Here we present 12 novel mutations in SALL1 associated with Townes-Brocks syndrome in 13 unrelated families. These include three nonsense mutations, three short insertions and six short deletions. Thus the number of SALL1 mutations increases to 35. Rare phenotypical features among mutation positive patients include hypothyroidism, vaginal aplasia with bifid uterus, cryptorchidism, bifid scrotum without hypospadia scrotalis, unilateral chorioretinal coloboma with loss of vision, dorsal hypoplasia of the corpus callosum, and umbilical hernia. (C) 2005 Wiley-Liss, Inc.