Seifert W, Holder-Espinasse M, Spranger S, Hoeltzenbein M, Rossier E, Dollfus H, Lacombe D, Verloes A, Chrzanowska K H, Maegawa G H B, Chitayat D, Kotzot D, Huhle D, Meinecke P, Albrecht B, Mathijssen I, Leheup B, Raile K, Hennies H C, Horn D
J Med Genet. 2006 May;43(5):e22. doi: 10.1136/jmg.2005.039867.
Cohen syndrome (CS) is an autosomal recessive disorder with variability in the clinical manifestations, characterised by mental retardation, postnatal microcephaly, facial dysmorphism, pigmentary retinopathy, myopia, and intermittent neutropenia. Mutations in the gene COH1 have been found in an ethnically diverse series of patients. Brief clinical descriptions of 24 patients with CS are provided. The patients were from 16 families of different ethnic backgrounds and between 2.5 and 60 years of age at assessment. DNA samples from all patients were analysed for mutations in COH1 by direct sequencing. Splice site mutations were characterised using reverse transcriptase PCR analysis from total RNA samples. In this series, we detected 25 different COH1 mutations; 19 of these were novel, including 9 nonsense mutations, 8 frameshift mutations, 4 verified splice site mutations, 3 larger in frame deletions, and 1 missense mutation. We observed marked variability of developmental and growth parameters. The typical facial gestalt was seen in 23/24 patients. Early onset progressive myopia was present in all the patients older than 5 years. Widespread pigmentary retinopathy was found in 12/14 patients assessed over 5 years of age. We present evidence for extended allelic heterogeneity of CS, with the vast majority of mutations leading to premature termination codons in COH1. Our data confirm the broad clinical spectrum of CS with some patients lacking even the characteristic facial gestalt and pigmentary retinopathy at school age.
科恩综合征（CS）是一种常染色体隐性疾病，临床表现具有变异性，其特征为智力发育迟缓、出生后小头畸形、面部畸形、色素性视网膜病变、近视和间歇性中性粒细胞减少症。在一系列不同种族的患者中发现了COH1基因的突变。本文提供了24例CS患者的简要临床描述。这些患者来自16个不同种族背景的家庭，评估时年龄在2.5岁至60岁之间。通过直接测序对所有患者的DNA样本进行COH1基因突变分析。使用来自总RNA样本的逆转录酶PCR分析来鉴定剪接位点突变。在该系列研究中，我们检测到25种不同的COH1突变；其中19种是新发现的，包括9种无义突变、8种移码突变、4种已证实的剪接位点突变、3种较大的框内缺失和1种错义突变。我们观察到发育和生长参数存在显著变异性。24例患者中有23例呈现典型的面部特征。所有5岁以上的患者均出现早发性进行性近视。在14例5岁以上接受评估的患者中，有12例发现广泛的色素性视网膜病变。我们提供了CS等位基因异质性扩展的证据，绝大多数突变导致COH1基因出现过早终止密码子。我们的数据证实了CS具有广泛的临床谱，一些患者在学龄期甚至缺乏典型的面部特征和色素性视网膜病变。
