Baquero-Montoya C, Gil-Rodríguez M C, Teresa-Rodrigo M E, Hernández-Marcos M, Bueno-Lozano G, Bueno-Martínez I, Remeseiro S, Fernández-Hernández R, Bassecourt-Serra M, Rodríguez de Alba M, Queralt E, Losada A, Puisac B, Ramos F J, Pié J
Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain; Service of Pediatrics, Hospital Clínico Universitario "Lozano Blesa", Zaragoza, Spain.
Clin Genet. 2014 May;85(5):446-51. doi: 10.1111/cge.12194. Epub 2013 Jun 17.
The disorders caused by mutations in genes encoding subunits and accessory proteins of cohesin complex are collectively termed as cohesinopathies. The best known cohesinopathy is Cornelia de Lange Syndrome (CdLS), which is a multisystem developmental disorder characterized by facial dysmorphism, limb malformations, growth and cognitive impairment. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), are responsible for ∼ 70% of CdLS cases. We describe a 16-year-old boy with facial dysmorphism, growth retardation, intellectual disability, hirsutism and small hands, who has a small Supernumerary Marker Chromosome (sSMC) present in mosaic form. sSMC is composed of two duplicated segments encompassing 17 genes including SMC1A gene, at the regions Xp11.22 and Xp11.21q11.1. Clinical comparison between our patient with a previously reported individual with a SMC1A duplication and four male carriers of similar sSMC reported in databases, suggest that they all share clinical features related to cohesinopathies. Although our patient does not have the classical CdLS craniofacial phenotype, he has pre and postnatal growth retardation, intellectual disability and mild musculoskeletal anomalies, features commonly seen in patients with cohesinopathies.
由黏连蛋白复合体的亚基和辅助蛋白编码基因突变引起的疾病统称为黏连蛋白病。最著名的黏连蛋白病是科妮莉亚·德朗格综合征（CdLS），它是一种多系统发育障碍，其特征为面部畸形、肢体畸形、生长和认知障碍。五个基因发生突变，即黏连蛋白复合体亚基（SMC1A、SMC3、RAD21）及其调节因子（NIPBL、HDAC8）的编码基因，约70%的CdLS病例是由这些基因突变所致。我们描述了一名16岁男孩，他有面部畸形、生长发育迟缓、智力残疾、多毛症和小手，其体内存在嵌合形式的小额外标记染色体（sSMC）。sSMC由两个重复片段组成，包含17个基因，包括位于Xp11.22和Xp11.21q11.1区域的SMC1A基因。将我们的患者与之前报道的一名SMC1A重复个体以及数据库中报道的四名类似sSMC男性携带者进行临床比较，结果表明他们都具有与黏连蛋白病相关的临床特征。虽然我们的患者没有典型的CdLS颅面表型，但他有产前和产后生长发育迟缓、智力残疾和轻度肌肉骨骼异常，这些都是黏连蛋白病患者常见的特征。
