[Analysis of clinical phenotypes and genetic variations in a Chinese family affected with craniofacial and skeletal deformities].

Objective: To identify pathogenic mutation in a pedigree affected with craniofacial and skeletal abnormalities featuring an autosomal dominant inheritance.

Methods: Clinical 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.

Results: A 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.

Conclusion: The 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.