The splice c.1815G>A variant in KIAA0586 results in a phenotype bridging short-rib-polydactyly and oral-facial-digital syndrome: A case report and literature review.

Dario Cocciadiferro, Emanuele Agolini, Maria Cristina Digilio, Lorenzo Sinibaldi, Marco Castori, Evelina Silvestri, Andrea Dotta, Bruno Dallapiccola, Antonio Novelli

Medicine 2020 Feb

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KIAA0586 variants have been associated to short-rib thoracic dysplasia, an autosomal recessive skeletal ciliopathy characterized by a narrow thorax, short limbs, and radiological skeletal abnormalities. Patients 1 and 2 were two Roma Gypsy siblings presenting thoracic dysplasia and a combination of oral cavity anomalies. A custom NGS gene panel, including genes associated to skeletal ciliopathies, identified the homozygous KIAA0586 splicing variant c.1815G>A (p.Gln605Gln) in both siblings, confirming the clinical diagnosis of short-rib-polydactyly. Patients were transferred to neonatal intensive care unit and received life-support treatment. Patients 1 and 2 died after few hours and 1 month of birth, respectively, because of respiratory failure related with the disease. We report two patients affected by short-rib polydactyly syndrome and overlapping phenotype with oral-facial-digital syndrome associated with the c.1815G>A variant in KIAA0586, suggesting a quite peculiar genotype-phenotype correlation.

Citation

Dario Cocciadiferro, Emanuele Agolini, Maria Cristina Digilio, Lorenzo Sinibaldi, Marco Castori, Evelina Silvestri, Andrea Dotta, Bruno Dallapiccola, Antonio Novelli. The splice c.1815G>A variant in KIAA0586 results in a phenotype bridging short-rib-polydactyly and oral-facial-digital syndrome: A case report and literature review. Medicine. 2020 Feb;99(8):e19169