De Novo and Inherited Mutations in COL4A2, Encoding the Type IV Collagen ¦Á2 Chain Cause Porencephaly

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• 作者：Yuriko Yoneda¹ ; Kazuhiro Haginoya² ; ³ ; Hiroshi Arai⁴ ; Shigeo Yamaoka⁵ ; Yoshinori Tsurusaki¹ ; Hiroshi Doi¹ ; Noriko Miyake¹ ; Kenji Yokochi⁶ ; Hitoshi Osaka⁷ ; Mitsuhiro Kato⁸ ; Naomichi Matsumoto¹ ; Hirotomo Saitsu¹ ; ^{hsaitsu@yokohama-cu.ac.jp}
• 刊名：The American Journal of Human Genetics
• 出版年：2012
• 出版时间：13 January 2012
• 年：2012
• 卷：90
• 期：1
• 页码：86-90
• 全文大小：550 K

文摘

Porencephaly is a neurological disorder characterized by fluid-filled cysts or cavities in the brain that often cause hemiplegia. It has been suggested that porencephalic cavities result from focal cerebral degeneration involving hemorrhages. De novo or inherited heterozygous mutations in COL4A1, which encodes the type IV ¦Á1 collagen chain that is essential for structural integrity for vascular basement membranes, have been reported in individuals with porencephaly. Most mutations occurred at conserved Gly residues in the Gly-Xaa-Yaa repeats of the triple-helical domain, leading to alterations of the ¦Á1¦Á1¦Á2 heterotrimers. Here we report on two individuals with porencephaly caused by a heterozygous missense mutation in COL4A2, which encodes the type IV ¦Á2 collagen chain. Mutations c.3455G>A and c.3110G>A, one in each of the individuals, cause Gly residues in the Gly-Xaa-Yaa repeat to be substituted as p.Gly1152Asp and p.Gly1037Glu, respectively, probably resulting in alterations of the ¦Á1¦Á1¦Á2 heterotrimers. The c.3455G>A mutation was found in the proband's mother, who showed very mild monoparesis of the left upper extremity, and the maternal elder uncle, who had congenital hemiplegia. The maternal grandfather harboring the mutation is asymptomatic. The c.3110G>A mutation occurred de novo. Our study confirmed that abnormalities of the ¦Á1¦Á1¦Á2 heterotrimers of type IV collagen cause porencephaly and stresses the importance of screening for COL4A2 as well as for COL4A1.