Am J Med Genet A. 2023 Jan 31. doi: 10.1002/ajmg.a.63134. Online ahead of print.
Pre-mRNA splicing factors are crucial in regulating transcript diversity, by removing introns from eukaryotic transcripts, an essential step in gene expression. Splicing of pre-mRNA is catalyzed by spliceosomes. CWC27 is a cyclophilin associated with spliceosome, in which genetic defects of its components have been linked to spliceosomopathies with clinical phenotypes including skeletal developmental defects, retinitis pigmentosa (RP), short stature, skeletal anomalies, and neurological disorders. We report two siblings (male and female) of Mexican descent with a novel homozygous frameshift variant in CWC27 and aim to highlight the cardinal features among the previously described 12 cases as well as expand the currently recognized phenotypic spectrum. Both siblings presented with a range of ocular and extraocular manifestations including novel features such as solitary kidney and tarsal coalition in the male sibling, together with gait abnormalities, and Hashimoto’s thyroiditis in the female sibling. Finally, we highlight ectodermal involvement including sparse scalp hair, eyebrows and lashes, pigmentary differences, nail dysplasia, and dental anomalies as a core phenotype associated with the CWC27 spliceosomopathy.