Hur David J, Raymond Gerald V, Kahler Stephen G, Riegert-Johnson Douglas L, Cohen Bernard A, Boyadjiev Simeon A
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Am J Med Genet A. 2005 May 15;135(1):36-40. doi: 10.1002/ajmg.a.30680.
Keutel syndrome (KS) [OMIM 245150] is a rare autosomal recessive condition, characterized by abnormal cartilage calcification. Mutations in the matrix Gla protein gene (MGP) have been previously reported in three unrelated KS families. MGP is an extracellular matrix protein that acts as a calcification inhibitor by repressing bone morphogenetic protein 2 (BMP2). Loss-of-function mutations of MGP result in abnormal calcification of the soft tissues, a cardinal feature of KS. We report the fourth MGP mutation (IVS2 + 1G > A) in a consanguineous Arab family, which results in the loss of the consensus donor splice site at the exon 2-intron 2 junction. In addition to the typical manifestations, we observed abnormalities in the white matter of the brain, optic nerve atrophy, and mid-dermal elastolysis in the affected individuals of this family. This report broadens the clinical phenotype observed in patients with KS. The effect of the IVS2 + 1G > A mutation is consistent with the previously reported loss-of-function mutations of MGP.
科伊特尔综合征（KS）[在线人类孟德尔遗传数据库编号245150]是一种罕见的常染色体隐性疾病，其特征为软骨钙化异常。此前在三个无亲缘关系的KS家族中报道了基质Gla蛋白基因（MGP）的突变。MGP是一种细胞外基质蛋白，通过抑制骨形态发生蛋白2（BMP2）发挥钙化抑制剂的作用。MGP的功能丧失突变导致软组织异常钙化，这是KS的主要特征。我们报道了一个近亲结婚的阿拉伯家族中的第四种MGP突变（IVS2 + 1G > A），该突变导致外显子2 - 内含子2连接处的共有供体剪接位点缺失。除了典型表现外，我们在这个家族的患病个体中还观察到脑白质异常、视神经萎缩和真皮中层弹性组织离解。本报告拓宽了KS患者中观察到的临床表型。IVS2 + 1G > A突变的影响与先前报道的MGP功能丧失突变一致。
