Clinical and genetic research in a Chinese family with Stickler syndrome type 1

Abstract

Background 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 1 （ 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 9 living families. Inheritance of this family complied 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, palatosehisis, etc. Mutation screening of COL2AI gene revealed that the first base of intron 12 was deleted（IVS12＋lG 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. Key words: Stickler syndrome; COL2A1 gene; Heredity; Gene mutation; Pedigree study