Analysis of clinical phenotypes and genetic variations in a Chinese family affected with craniofacial and skeletal deformities.
- Author:
Huihui SUN
1
;
Naijun WAN
Author Information
- Publication Type:Journal Article
- MeSH: Asian Continental Ancestry Group; genetics; Craniofacial Abnormalities; genetics; Female; Genetic Testing; methods; Heterozygote; Humans; Infant; Male; Mutation; genetics; Pedigree
- From: Chinese Journal of Medical Genetics 2016;33(6):768-772
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo identify pathogenic mutation in a pedigree affected with craniofacial and skeletal abnormalities featuring an autosomal dominant inheritance.
METHODSClinical data and peripheral venous blood samples of the pedigree were collected. A total of 326 exons of skeletal disease-related genes were screened using Roche NimbleGen probes, and the results were confirmed by Sanger sequencing. Suspected variants were analyzed by bioinformatic software.
RESULTSA novel heterozygous mutation c.480C>A (p.160K>N) of HDAC4, the pathogenic gene for brachydactyly mental retardation syndrome, was found in the affected proband, his father and uncle. The proband and his father also carried a novel heterozygous c.880-882delAAG (p.294delK) mutation of TRPS1, the pathogenic gene for tricho-rhino-phalangeal syndrome. Bioinformatic analysis suggested that both mutations are pathogenic. In addition, three novel genetic variants, namely c.4817G>A (p.1606S>L) of MLL2, c.83A>G (p.28H>R) of TP63, and c.1712G>C (p.571T>S) of ERCC2, were also identified in this family.
CONCLUSIONThe HDAC4 c.480C>A (p.160K>N) mutation probably underlies the disease in this pedigree, while the TRPS1 c.880-882delAAG (p.294delK) mutation may be related with certain features of the affected family members. Genetic analysis has facilitated the diagnosis of this complex disease.