title: Targeted next-generation sequencing identifies novel compound heterozygous mutations of DYNC2H1 in a fetus with short rib-polydactyly syndrome, type III.
abstract: A 26-year-old woman with a past history of fetal skeletal dysplasia was referred to our institution at 24weeks of gestation following a routine sonographic diagnosis of short limbs in the fetus. A fetal ultrasound showed short limbs, a narrow thorax, short ribs with marginal spurs, and polydactyly. Conventional cytogenetics analysis of cultured amniocytes demonstrated that the fetal karyotype was normal. Using targeted exome sequencing of 226 known genes implicated in inherited skeletal dysplasia, we identified compound heterozygous mutations in the DYNC2H1 gene in the fetus with short rib-polydactyly syndrome, type III (SRPS III), c.1151 C>T(p.Ala384Val) and c.4351 C>T (p.Gln1451*), which were inherited from paternally and maternally, respectively. These variants were further confirmed using Sanger sequencing and have not been previously reported. To our knowledge, this is the first report of DYNC2H1 mutations causing SRPS III, in the Chinese population. Our findings expand the number of reported cases of this rare disease, and indicate that targeted next-generation sequencing (NGS) is an accurate, rapid, and cost-effective method in the genetic diagnosis of fetal skeletal dysplasia.
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Libin
authors.initials: L
authors.lastname: Mei
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Su
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Quan
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China. Electronic address: liangdesheng@sklmg.edu.cn.
authors.forename: Desheng
authors.initials: D
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China. Electronic address: wulingqian@sklmg.edu.cn.
authors.forename: Lingqian
authors.initials: L
authors.lastname: Wu
mesh_terms: D000328:Adult; D001483:Base Sequence; D056445:Cytoplasmic Dyneins / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012779:Short Rib-Polydactyly Syndrome / Q000000981:diagnostic imaging / Q000235:genetics*; D014463:Ultrasonography
chemical_list: C099883:DYNC2H1 protein, human; D056445:Cytoplasmic Dyneins
keywords: Compound heterozygous mutations; DYNC2H1; Short rib-polydactyly syndrome; Targeted next-generation sequencing; Type III