title: Recessive LAMC3 mutations cause malformations of occipital cortical development.
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.
authors.affiliation: Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Tanyeri
authors.initials: T
authors.lastname: Barak
authors.forename: Kenneth Y
authors.initials: KY
authors.lastname: Kwan
authors.forename: Angeliki
authors.initials: A
authors.lastname: Louvi
authors.forename: Veysi
authors.initials: V
authors.lastname: Demirbilek
authors.forename: Serap
authors.initials: S
authors.lastname: Saygı
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tüysüz
authors.forename: Murim
authors.initials: M
authors.lastname: Choi
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Boyacı
authors.forename: Katja
authors.initials: K
authors.lastname: Doerschner
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.forename: Hande
authors.initials: H
authors.lastname: Kaymakçalan
authors.forename: Saliha
authors.initials: S
authors.lastname: Yılmaz
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bakırcıoğlu
authors.forename: Ahmet Okay
authors.initials: AO
authors.lastname: Cağlayan
authors.forename: Ali Kemal
authors.initials: AK
authors.lastname: Oztürk
authors.forename: Katsuhito
authors.initials: K
authors.lastname: Yasuno
authors.forename: William J
authors.initials: WJ
authors.lastname: Brunken
authors.forename: Ergin
authors.initials: E
authors.lastname: Atalar
authors.forename: Cengiz
authors.initials: C
authors.lastname: Yalçınkaya
authors.forename: Alp
authors.initials: A
authors.lastname: Dinçer
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bronen
authors.forename: Shrikant
authors.initials: S
authors.lastname: Mane
authors.forename: Tayfun
authors.initials: T
authors.lastname: Ozçelik
authors.forename: Richard P
authors.initials: RP
authors.lastname: Lifton
authors.forename: Nenad
authors.initials: N
authors.lastname: Sestan
authors.forename: Kaya
authors.initials: K
authors.lastname: Bilgüvar
authors.forename: Murat
authors.initials: M
authors.lastname: Günel
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism; D003241:Consanguinity; D017353:Gene Deletion; D005808:Genes, Recessive; D006801:Humans; D007797:Laminin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D009154:Mutation; D009778:Occipital Lobe / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D013045:Species Specificity
chemical_list: C504218:LAMC3 protein, human; C504220:Lamc3 protein, mouse; D007797:Laminin