Targeted gene panel sequencing prenatally detects two novel mutations of <i>DYNC2H1</i> in a fetus with increased biparietal diameter and polyhydramnios

<jats:sec><jats:title>Background</jats:title><jats:p>Genetic skeletal disorders (GSDs) are clinically and genetically heterogeneous with more than 350 genes accounting for the diversity of disease phenotypes. Prenatal diagnosis of these disorders has been challenging because of the limited but variable prenatal phenotypes, highlighting the need of a novel genetic approach. Short‐rib polydactyly syndrome (SRPS) Type III is an autosomal recessive GSD characterized by extreme narrowness of the thorax, severely shortened tubular bones, polydactyly and multiple malformations.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Cytogenetic and molecular analyses using GTG‐banding, single nucleotide polymorphism array and a novel GSDs targeted gene panel sequencing were performed in a 24 weeks fetus with increased biparietal diameter (BPD), short limbs, narrow thorax and polyhydramnios.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>No chromosomal abnormalities and pathogenic copy number variations (CNVs) were detected in the fetus. Two novel compound heterozygous mutations c.2992C > T and c.12836G > C in the <jats:italic>DYNC2H1</jats:italic> gene were identified by targeted genes panel sequencing. A literature review was performed to delineate the prenatal phenotype of SRPS Type III.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This is the first report of prenatal diagnosis of <jats:italic>DYNC2H1</jats:italic> mutations causing SRPS Type III in a fetus with increased BPD associated with polyhydramnios in China. Our findings expand the mutation spectrum of <jats:italic>DYNC2H1</jats:italic> in this rare disease and demonstrate that targeted gene panel capture followed by next‐generation sequencing (NGS) is an efficient and cost‐effective method to perform a molecular prenatal diagnosis of a rare genetic skeletal disorder.</jats:p></jats:sec>