摘要背景 Stickler综合征是一种遗传性结缔组织病,主要以眼部、关节、口面部及听力损伤为特征.确定Stickler综合征的基因突变位点能够为该综合征的基因诊断和治疗提供依据. 目的 研究一个Ⅰ型Stickler综合征家系的临床特征并确定致病基因突变. 方法 对一个患Ⅰ型Stickler综合征的家系进行临床研究和系谱分析.采集Stickler综合征家系中3例患者和6位表型正常者的外周血标本,采用PCR法扩增COL2A1基因的全部外显子及其侧翼,对扩增产物进行直接测序,结果与Genbank中相应序列进行比对.同时检测100位无亲缘关系的正常人外周血标本进行对照. 结果 该家系共4代11位成员,2位成员去世,其中包括1例患病者.现存的9位成员中共3例患者,调查显示该家系符合常染色显性遗传方式.3例患者的临床特点包括高度近视、膜型玻璃体异常及面中部扁平、短鼻、腭裂等,符合Ⅰ型Stickler综合征的临床诊断.COL2A1基因突变筛查结果显示,该家系中3例患者COL2A1基因内含子12的第一个碱基发生了单个碱基缺失(IVS12+1G del)的杂合性剪接位点突变,核苷酸序列分析结果证实该突变致提前形成终止密码子,形成一种包括306个氨基酸在内的截短蛋白,导致该基因的功能异常,而家系中表型正常者及无亲缘关系的正常对照者均未发现该基因突变. 结论 本研究确定了一个Ⅰ型Stickler家系,并在该家系确定了一个新的COL2A1基因突变,这是中国首次报道Stickler综合征家系的基因突变.

abstractsBackground Stickler syndrome is a genetic connective tissue disorder that affects the ocular,skeletal,orofacial and auditory systems.To determine the gene mutation loci can offer a basis for genetic diagnosis and management of Stickler syndrome.Objective The aim of this study was to research the clinical characteristics of a pedigree with Stickler syndrome and identify the disease-causing gene mutation.Methods This study was approved by Ethic Committee of Peking Union Medical College Hospital.The clinical study and pedigree analysis were performed in one family with Stickler syndrome type Ⅰ (STL Ⅰ).Nine family members were examined with informed consent.The entire coding regions of COL2A1 gene with flanking intronic regions were amplified by PCR and directly sequenced.The detected sequence change was confirmed to be mutationloci by examining whether they existed in normal control individuals.Mutant proteins were predicted with online software.Results There were 4 generations and 11 members in this family,and 2 members died,including 1 patient.Three patients were found in 9living families.Inheritance of this family complicd with an autosomal dominant inheritance mode.All affected individuals showed the consistent phenotypes with STL Ⅰ,including high myopia,membranous vitreous anomaly and surface central flat,short nose,palatoschisis,etc.Mutation screening of COL2A1 gene revealed that the first base of intron 12 was deleted(IVS12+1G del).Nucleotide sequence analysis showed that this mutation led to the functional abnormal of this gene by forming termination cordon in advance.This mutation occurred in all affected individuals,however,no mutation was observed in any unaffected member or 100 normal unrelated individuals.Conclusions This study identifies a novel splice-site mutation(IVS12+ 1G del)in COL2A1 gene in a Chinese STL Ⅰ pedigree.This is the first report on a mutation in a Chinese STL Ⅰ family.