ABSTRACT Short rib‐polydactyly syndrome (SRPS), with or without polydactyly, encompasses a range of autosomal recessive skeletal dysplasias characterized by shortened limbs, narrow thorax, and visceral abnormalities. Accurate genetic testing is crucial for the diagnosis and treatment of different clinical subtypes. This study investigates gene variants associated with the clinical features in a Chinese family affected by short rib‐polydactyly syndrome (SRPS), DYNC2I1 ‐related. A retrospective analysis of two adverse pregnancy histories in the family was conducted using genetic testing methods, including clinical exome sequencing, Sanger sequencing, amniotic fluid cell karyotype analysis, and chromosomal microarray analysis. Variants detected in the family were scored and classified according to ACMG guidelines, and a systematic analysis of clinically relevant variants was performed. A homozygous variant in the DYNC2I1 gene, NM₀18051. 5: c. 1526A>T p. (Asp509Val), was identified in both fetuses affected by polydactyly and short rib‐polydactyly syndrome in the family and inherited from asymptomatic parents, consistent with a recessive inheritance pattern. This variant has not been reported in HGMD or PubMed and is classified as likely pathogenic according to ACMG guidelines. Based on PolyPhen‐2 and PROVEAN pathogenicity predictions, it is considered a deleterious variant. We report a novel homozygous variant in the DYNC2I1 gene inherited from asymptomatic parents. This finding expands the spectrum of genetic variants seen in SRPS patients related to DYNC2I1 and demonstrates the feasibility of clinical exome sequencing for prenatal diagnosis of SRPS.
Xian et al. (Tue,) studied this question.