Recessive LAMC3 mutations cause malformations of occipital cortical development

Tanyeri Barak, Kenneth Y. Kwan, Angeliki Louvi, Veysi Demirbilek, Serap Saygi, Beyhan Tüysüz, Murim Choi, Hüseyin Boyaci, Katja Doerschner, Ying Zhu, Hande Kaymakçalan, Saliha Yilmaz, Mehmet Bakircǧlu, Ahmet Okay Çaǧlayan, Ali Kemal Öztürk, Katsuhito Yasuno, William J. Brunken, Ergin Atalar, Cengiz Yalçnkaya, Alp DinçerRichard A. Bronen, Shrikant Mane, Tayfun Özçelik, Richard P. Lifton, Nenad Šestan, Kaya Bilgüvar, Murat Günel

Research output: Contribution to journalArticle

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 33 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.

Original languageEnglish (US)
Pages (from-to)590-594
Number of pages5
JournalNature Genetics
Volume43
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Barak, T., Kwan, K. Y., Louvi, A., Demirbilek, V., Saygi, S., Tüysüz, B., Choi, M., Boyaci, H., Doerschner, K., Zhu, Y., Kaymakçalan, H., Yilmaz, S., Bakircǧlu, M., Çaǧlayan, A. O., Öztürk, A. K., Yasuno, K., Brunken, W. J., Atalar, E., Yalçnkaya, C., ... Günel, M. (2011). Recessive LAMC3 mutations cause malformations of occipital cortical development. Nature Genetics, 43(6), 590-594. https://doi.org/10.1038/ng.836