Intractable Rare Dis Res. 2020;9(2):95-98. (DOI: 10.5582/irdr.2020.01031)

Identification of novel compound heterozygous mutations of the DYNC2H1 gene in a fetus with short-rib thoracic dysplasia 3 with or without polydactyly

Geng K, Mu K, Zhao Y, Luan J, Cui Y, Han J


A prenatal sonograph revealed a 26-week-old fetus with short limbs and a narrow chest in a 23-year-old woman with a history of fetal skeletal dysplasia. A single nucleotide polymorphismbased chromosomal microarray (CMA) indicated a normal karyotype, and no chromosomal segments with abnormal copy numbers were noted in the fetus. Whole exome sequencing identified compound heterozygous mutations in the DYNC2H1 gene responsible for a lethal type of bone growth disorder, short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3), and revealed a missense mutation c.515C>A (p. Pro172Gln) of paternal origin and a missense mutation c.5983G>A (p. Ala1995Thr) of maternal origin. These variants were further confirmed by Sanger sequencing. To the extent known, the c.515C>A (p. Pro172Gln) mutation is novel for SRTD3, and the site is conserved across species. This study found a novel mutation of the DYNC2H1 gene for SRTD3 and it has increased the number of reported cases and expanded the spectrum of mutations causing this rare disease.

KEYWORDS: short-rib thoracic dysplasia 3 with or without polydactyly, DYNC2H1, compound heterozygous mutations

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