Clinical characteristics and pathogenic gene analysis in a large pedigree with multiple epiphyseal dysplasia
10.3760/cma.j.issn.0253-2352.2020.02.005
- VernacularTitle: 一个多发性骨骺发育不良大家系的临床特点及致病基因分析
- Author:
Guiyu LOU
1
,
2
,
3
;
Na QI
;
Ke YANG
;
Litao QIN
;
Yuwei ZHANG
;
Shixiu LIAO
Author Information
1. Institution of Medical Genetics of Henan Provincial People's Hospital, Henan Province Key Laboratory of Functional Genes for Hereditary Diseases
2. People's Hospital of Zhengzhou University
3. People's Hospital of Henan University, Zhengzhou 450002, China
- Publication Type:Journal Article
- Keywords:
Osteochondrodysplasias;
Pedigree;
DNA, intergenic;
DNA mutational analysis
- From:
Chinese Journal of Orthopaedics
2020;40(2):97-102
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To provide experimental evidence for genetic counseling and prenatal molecular diagnosis by analyzing the clinical characteristics and screening for pathogenic genes of a five-generation suspected multiple epiphyseal dysplasia (MED) family (17 patients).
Methods:The family members' medical history, general physical examination and hip joint X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA were extracted from these samples. The exons of clinical genes from probands' DNA were sequenced by High throughput sequencing method. Next Gene software was used to compare and analyze the sequence and INGENUITY software was further used to annotate the mutations in order to find the pathogenic mutations in probands. The suspicious mutations were confirmed in pedigree members by PCR and Sanger sequencing.
Results:The family consisted of 5 generations and 38 members. Pedigree analysis was consistent with autosomal dominant inheritance. There were 17 patients in the family, and their clinical manifestations showed abnormal walking posture in childhood, pain in hip and knee joints, and typical pathological changes of epiphyseal dysplasia on X-ray. Cartilage oligomeric matrix protein (COMP) gene c.1153G>A (p.Asp385Asn) missense heterozygous mutation was screened in proband, which was genotypically and phenotypically segregated in the pedigree.
Conclusion:A missense mutation of the comp gene has been identified in a pedigree affected with MED which was the first reported in a big family. Our result is conducive to the further diagnosis and treatment and also provides a molecular basisfor the future prenatal diagnosis.
