Recessive LAMC3 mutations cause malformations of occipital cortical development

Nat Genet. 2011 Jun;43(6):590-4. doi: 10.1038/ng.836.

Tanyeri Barak ¹, Kenneth Y Kwan, Angeliki Louvi, Veysi Demirbilek, Serap Saygı, Beyhan Tüysüz, Murim Choi, Hüseyin Boyacı, Katja Doerschner, Ying Zhu, Hande Kaymakçalan, Saliha Yılmaz, Mehmet Bakırcıoğlu, Ahmet Okay Cağlayan, Ali Kemal Oztürk, Katsuhito Yasuno, William J Brunken, Ergin Atalar, Cengiz Yalçınkaya, Alp Dinçer, Richard A Bronen, Shrikant Mane, Tayfun Ozçelik, Richard P Lifton, Nenad Sestan, Kaya Bilgüvar, Murat Günel

Affiliations

Affiliation

1 Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, USA.

PMID: 21572413 DOI: 10.1038/ng.836

Abstract

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 γ3 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.

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