Allelic heterogeneity in the COH1 gene explains clinical variability in Cohen syndrome
Allelic heterogeneity in the COH1 gene explains clinical variability in Cohen syndrome
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DOI：
10.1086/422219
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发表时间：
2004-07-01
影响因子：
9.8
通讯作者：
Horn, D
中科院分区：
文献类型：
--
作者：
Hennies, HC;Rauch, A;Horn, D
Cohen综合征是一种罕见的常染色体隐性遗传疾病，临床表现多样，主要表现为发育迟缓、智力低下、小头畸形、典型的面部畸形、进行性色素性视网膜病变、严重近视和间歇性中性粒细胞减少。科恩综合征基因定位于芬兰患者的染色体8 q22，最近，在芬兰和北方和西欧其他地区的科恩综合征患者中报告了基因COH 1的突变。在这里，我们描述了来自巴西、德国、黎巴嫩、阿曼、波兰和土耳其的12个家族的20例科恩综合征患者的临床和分子研究结果。所有患者均为COH 1突变纯合子或复合杂合子。我们共发现了17个新的突变，大多数导致提前终止密码子。临床表现高度可变。不同程度的发育迟缓、早发性近视、关节松弛和面部畸形是所有患者的唯一特征;然而，学龄期视网膜病变、小头畸形和中性粒细胞减少症不是科恩综合征的必要症状。在一组不同种族的患者中发现COH 1的新突变，证明了广泛的等位基因异质性，并解释了科恩综合征有趣的临床变异性。
Cohen syndrome is a rare autosomal recessive disorder with a variable clinical picture mainly characterized by developmental delay, mental retardation, microcephaly, typical facial dysmorphism, progressive pigmentary retinopathy, severe myopia, and intermittent neutropenia. A Cohen syndrome locus was mapped to chromosome 8q22 in Finnish patients, and, recently, mutations in the gene COH1 were reported in patients with Cohen syndrome from Finland and other parts of northern and western Europe. Here, we describe clinical and molecular findings in 20 patients with Cohen syndrome from 12 families, originating from Brazil, Germany, Lebanon, Oman, Poland, and Turkey. All patients were homozygous or compound heterozygous for mutations in COH1. We identified a total of 17 novel mutations, mostly resulting in premature termination codons. The clinical presentation was highly variable. Developmental delay of varying degree, early-onset myopia, joint laxity, and facial dysmorphism were the only features present in all patients; however, retinopathy at school age, microcephaly, and neutropenia are not requisite symptoms of Cohen syndrome. The identification of novel mutations in COH1 in an ethnically diverse group of patients demonstrates extensive allelic heterogeneity and explains the intriguing clinical variability in Cohen syndrome.