BMP4 loss-of-function mutations in developmental eye disorders including SHORT syndrome.
BMP4 loss-of-function mutations in developmental eye disorders including SHORT syndrome.
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DOI：
10.1007/s00439-011-0968-y
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发表时间：
2011-10
期刊：
影响因子：
5.3
通讯作者：
Semina EV
中科院分区：
文献类型：
--
作者：
Reis LM;Tyler RC;Schilter KF;Abdul-Rahman O;Innis JW;Kozel BA;Schneider AS;Bardakjian TM;Lose EJ;Martin DM;Broeckel U;Semina EV
BMP4 功能丧失突变和缺失已被证明与眼睛、数字和大脑异常相关，但由于这些报告很少，人类 BMP4 突变的完整表型谱尚不清楚。我们对 133 名患有各种眼部疾病的患者进行了 BMP4 编码区突变或基因组缺失筛查。在两名患者中检测到 BMP4 缺失：一名患有短路综合征的患者和一名患有眼前段异常并伴有颅面畸形和认知障碍的患者。除此之外，还发现了三个基因内 BMP4 突变。一名患有无眼症、小眼症伴有巩膜角膜、右侧膈疝和脑积水的患者被发现在 BMP4 中存在 c.592C>T (p.R198X) 无义突变。移码突变 c.171dupC (p.E58RfsX17) 在两个患有无眼症/小眼症、发育迟缓/轴后多指畸形和生长不良的同父异母兄弟姐妹及其未受影响的母亲中被发现；一名受影响的兄弟姐妹在第二个等位基因中携带额外的 BMP4 突变，c.362A>G (p.H121R)。这是第一份表明 BMP4 在 SHORT 综合征、Axenfeld-Rieger 畸形、生长迟缓、大头畸形和膈疝中发挥作用的报告。这些结果显着增加了报道的功能丧失突变的数量，进一步支持了 BMP4 在眼部发育中的关键作用，并提供了 BMP4 突变的可变表达/非外显率的额外证据。
BMP4 loss-of-function mutations and deletions have been shown to be associated with ocular, digital, and brain anomalies, but due to the paucity of these reports, the full phenotypic spectrum of human BMP4 mutations is not clear. We screened 133 patients with a variety of ocular disorders for BMP4 coding region mutations or genomic deletions. BMP4 deletions were detected in two patients: a patient affected with SHORT syndrome and a patient with anterior segment anomalies along with craniofacial dysmorphism and cognitive impairment. In addition to this, three intragenic BMP4 mutations were identified. A patient with anophthalmia, microphthalmia with sclerocornea, right-sided diaphragmatic hernia, and hydrocephalus was found to have a c.592C>T (p.R198X) nonsense mutation in BMP4. A frameshift mutation, c.171dupC (p.E58RfsX17), was identified in two half-siblings with anophthalmia/microphthalmia, discordant developmental delay/postaxial polydactyly, and poor growth as well as their unaffected mother; one affected sibling carried an additional BMP4 mutation in the second allele, c.362A>G (p.H121R). This is the first report indicating a role for BMP4 in SHORT syndrome, Axenfeld–Rieger malformation, growth delay, macrocephaly, and diaphragmatic hernia. These results significantly expand the number of reported loss-of-function mutations, further support the critical role of BMP4 in ocular development, and provide additional evidence of variable expression/non-penetrance of BMP4 mutations.
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影响因子：
10.5
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Jiao, K;Kulessa, H;Hogan, BLM
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