Genetic analysis of a pedigree of DYNC2H1 gene variation-caused short rib polydactyly syndrome type Ⅲ / 中华围产医学杂志

ABSTRACT

This paper reported the genetic analysis of a pedigree in which three affected fetuses with short limbs were revealed by first-trimester ultrasonography in three consecutive pregnancies. Tissues of the second aborted fetus were collected and analyzed by chromosome karyotype analysis and whole exome sequencing. The results indicated compound heterozygous mutations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene. Real-time fluorescence quantitative polymerase chain reaction and Sanger sequencing further confirmed that the two variants were inherited from the father and the mother with normal phenotypes, respectively. EX64-EX83 Del was a likely pathogenic variant and c.8190G>T was a variant of uncertain significance. Based on the above results and the medical history, it was highly suspected that the fetus had autosomal recessive short rib polydactyly syndrome type Ⅲ caused by compound heterozygous variants. Real-time fluorescent quantitative polymerase chain reaction and Sanger sequencing results of the third aborted fetus were consistent with the second fetus. Given the same phenotypes of fetuses in the second and third pregnancy, it was strongly suggested that the heterozygous variations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene were the pathogenic variants in this pedigree.