Mutations in LAMB1 Cause Cobblestone Brain Malformation without Muscular or Ocular Abnormalities

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• 作者：Farid Radmanesh¹ ; ² ; ¹² ; Ahmet Okay Caglayan³ ; ¹² ; Jennifer L. Silhavy¹ ; ² ; Cahide Yilmaz⁴ ; Vincent Cantagrel¹ ; ² ; Tarek Omar⁵ ; Ba?ak Rosti¹ ; ² ; Hande Kaymakcalan⁶ ; Stacey Gabriel⁷ ; Mingfeng Li⁸ ; Nenad &Scaron ; estan⁸ ; Kaya Bilguvar³ ; William B. Dobyns⁹ ; ¹⁰ ; Maha S. Zaki¹¹ ; Murat Gunel³ ; ^{murat.gunel@yale.edu} ; Joseph G. Gleeson¹ ; ² ; ^{jogleeson@ucsd.edu}
• 刊名：The American Journal of Human Genetics
• 出版年：2013
• 出版时间：7 March, 2013
• 年：2013
• 卷：92
• 期：3
• 页码：468-474
• 全文大小：991 K

文摘

Cobblestone brain malformation (COB) is a neuronal migration disorder characterized by protrusions of neurons beyond the first cortical layer at the pial surface of the brain. It is usually seen in association with dystroglycanopathy types of congenital muscular dystrophies (CMDs) and ocular abnormalities termed muscle-eye-brain disease. Here we report homozygous deleterious mutations in LAMB1, encoding laminin subunit beta-1, in two families with autosomal-recessive COB. Affected individuals displayed a constellation of brain malformations including cortical gyral and white-matter signal abnormalities, severe cerebellar dysplasia, brainstem hypoplasia, and occipital encephalocele, but they had less apparent ocular or muscular abnormalities than are typically observed in COB. LAMB1 is localized to the pial basement membrane, suggesting that defective connection between radial glial cells and the pial surface mediated by LAMB1 leads to this malformation.