A novel SIX3 mutation segregates with holoprosencephaly in a large family.
A novel SIX3 mutation segregates with holoprosencephaly in a large family.
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DOI：
10.1002/ajmg.a.32813
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发表时间：
2009-05
影响因子：
2
通讯作者：
Muenke, Maximilian
中科院分区：
文献类型：
--
作者：
Solomon, Benjamin D.;Lacbawan, Felicitas;Jain, Mahim;Domene, Sabina;Roessler, Erich;Moore, Cynthia;Dobyns, William B.;Muenke, Maximilian
前脑无裂畸形是人类最常见的前脑结构畸形，病因复杂，包括染色体畸变、单基因突变和环境因素。在此，我们介绍了 15 年前在对患有先天异常的女婴进行评估和随后的基因检查后确定的一个异常大的亲属成员中的相关临床发现。全基因组扫描和连锁分析仅显示出与 2 号染色体标记连锁的暗示性证据，这是几种谱系解释中最有可能的一种。我们现在报道，SIX3 前脑无裂畸形基因中的一种新的错义突变可能是该家族的原因。分子遗传学分析和/或临床特征现在表明，该家族中至少有 15 名成员被推测为 SIX3 突变基因携带者，其临床表现范围从表型正常成人（非外显率）到与出生后生活不相容的无叶前脑无裂畸形。这个特殊的家族代表了前脑无裂畸形基因突变的可变表现以及在阐明其过程中遇到的困难的重要例子。
Holoprosencephaly is the most common structural malformation of the forebrain in humans and has a complex etiology including chromosomal aberrations, single gene mutations and environmental components. Here we present the pertinent clinical findings among members of an unusually large kindred ascertained over 15 years ago following the evaluation and subsequent genetic work-up of a female infant with congenital anomalies. A genome-wide scan and linkage analysis showed only suggestive evidence of linkage to markers on chromosome 2 among the most likely of several pedigree interpretations. We now report that a novel missense mutation in the SIX3 holoprosencephaly gene is the likely cause in this family. Molecular genetic analysis and/or clinical characterization now show that at least 15 members of this family are presumed SIX3 mutation gene carriers, with clinical manifestations ranging from phenotypically normal adults (non-penetrance) to alobar holoprosencephaly incompatible with postnatal life. This particular family represents a seminal example of the variable manifestations of gene mutations in holoprosencephaly and difficulties encountered in their elucidation.
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影响因子：
64.8
作者：
Del Bene, F;Tessmar-Raible, K;Wittbrodt, J
通讯作者：
Wittbrodt, J
影响因子：
5.3
作者：
Bendavid, C;Dubourg, C;David, V
通讯作者：
David, V
DOI：
10.1002/tera.1420160304
发表时间：
1977-01-01
期刊：
TERATOLOGY
影响因子：
--
作者：
MATSUNAGA, E;SHIOTA, K
通讯作者：
SHIOTA, K
影响因子：
9.8
作者：
Kong, A;Cox, NJ
通讯作者：
Cox, NJ
影响因子：
30.8
作者：
Brown, SA;Warburton, D;Muenke, M
通讯作者：
Muenke, M