Recessive LAMC3 mutations cause malformations of occipital cortical development

被引：86

作者：

Barak, Tanyeri ^{[1
,2
,3
,4
]}

Kwan, Kenneth Y. ^{[2
,5
]}

Louvi, Angeliki ^{[1
,2
]}

Demirbilek, Veysi ^{[6
]}

Saygi, Serap ^{[7
]}

Tuysuz, Beyhan ^{[8
]}

Choi, Murim ^{[3
,4
]}

Boyaci, Huseyin ^{[9
,10
]}

Doerschner, Katja ^{[9
,10
]}

Zhu, Ying ^{[2
,5
]}

Kaymakcalan, Hande ^{[11
]}

Yilmaz, Saliha ^{[1
,2
,3
,4
]}

Bakircioglu, Mehmet ^{[1
,2
,3
,4
]}

Caglayan, Ahmet Okay ^{[1
,2
,3
,4
]}

Ozturk, Ali Kemal ^{[1
,2
,3
,4
]}

Yasuno, Katsuhito ^{[1
,2
,3
,4
]}

Brunken, William J. ^{[12
,13
]}

Atalar, Ergin ^{[10
]}

Yalcinkaya, Cengiz ^{[6
]}

Dincer, Alp ^{[14
]}

Bronen, Richard A. ^{[1
,15
]}

Mane, Shrikant ^{[3
,4
,16
]}

Ozcelik, Tayfun ^{[17
]}

Lifton, Richard P. ^{[3
,4
,18
]}

Sestan, Nenad ^{[2
,5
]}

Bilguevar, Kaya ^{[1
,2
,3
,4
]}

Guenel, Murat ^{[1
,2
,3
,4
]}

机构：

[1] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA

[3] Yale Univ, Sch Med, Dept Genet, Ctr Human Genet & Genom, New Haven, CT 06510 USA

[4] Yale Univ, Sch Med, Program Neurogenet, New Haven, CT USA

[5] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT USA

[6] Istanbul Univ, Cerrahpasa Fac Med, Dept Neurol, Div Child Neurol, Istanbul, Turkey

[7] Hacettepe Univ, Sch Med, Dept Neurol, Ankara, Turkey

[8] Istanbul Univ, Cerrahpasa Fac Med, Dept Pediat, Div Genet, Istanbul, Turkey

[9] Bilkent Univ, Dept Psychol, Ankara, Turkey

[10] Bilkent Univ, Natl Magnet Resonance Res Ctr, Ankara, Turkey

[11] Bahcesehir Univ, Fac Arts & Sci, Istanbul, Turkey

[12] Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA

[13] Suny Downstate Med Ctr, Dept Ophthalmol, Brooklyn, NY 11203 USA

[14] Acibadem Univ, Sch Med, Dept Radiol, Istanbul, Turkey

[15] Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06510 USA

[16] Yale Univ, Sch Med, Yale Ctr Genome Anal, New Haven, CT USA

[17] Bilkent Univ, Fac Sci, Dept Mol Biol & Genet, Ankara, Turkey

[18] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 06期

基金：

美国国家卫生研究院;

关键词：

HUMAN PREFRONTAL CORTEX; LAMININ GAMMA-3 CHAIN; EXPRESSION; NEURONS; POLYMICROGYRIA; MORPHOGENESIS; DIFFUSION; MIGRATION; MEMBRANE; ADULT;

D O I：

10.1038/ng.836

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

The biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin. 3 gene, leading to an immediate premature termination codon. In two other affected individuals with nearly identical phenotypes, we identified a homozygous nonsense mutation and a compound heterozygous mutation. In human but not mouse fetal brain, LAMC3 is enriched in postmitotic cortical plate neurons, localizing primarily to the somatodendritic compartment. LAMC3 expression peaks between late gestation and late infancy, paralleling the expression of molecules that are important in dendritogenesis and synapse formation. The discovery of the molecular basis of this unusual occipital malformation furthers our understanding of the complex biology underlying the formation of cortical gyrations.

引用

页码：590 / +

页数：7

共 37 条

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A developmental and genetic classification for malformations of cortical development [J].