Biallelic variants in NUDCD2 associated with a multiple malformation syndrome with cholestasis and renal failure

• Published in: American journal of medical genetics. Part A Vol. 191; no. 9; pp. 2324 - 2328
• Main Authors: Scheuerle, Angela E., Ni, Min, Ahmad, Aaliya A., Timmons, Charles F., Rakheja, Dinesh, Gordon, Erin E., Boothe, Megan
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-09-2023; Wiley Subscription Services, Inc
• Subjects: Aortic valve; Cell migration; Cholestasis; Cohesin; Fibroblasts; Heat shock proteins; Hsp90 protein; Hypoplasia; Hypothyroidism; immotile cilia; Liver diseases; Neural coding; NUDCD2; NudCL2; Phenotypes; Renal failure; situs inversus; Stenosis; renal failure; immotile cilia; NUDCD2; NudCL2; cholestasis; situs inversus
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.63314

NudC‐like protein 2 (NUDCD2) is a 4‐exon protein‐coding gene at 5q34. The protein appears to act in concert with other genes regulating cell migration and microtubule extension. Early studies in model organisms show associations with LIS1, HERC2, and cohesin subunits via a co‐chaperone function with Heat shock protein 90 (Hsp90). It is a candidate gene for human pathology. We present two unrelated patients with biallelic variants in NUDCD2. Their phenotypes comprise similar dysmorphic facies, midline brain hypoplasia, hypothyroidism, pulmonary and aortic valve stenosis, severe dysfunction of the liver and kidneys, profound hypotonia, and early death. The cellular analysis demonstrates the absence of the NUDCD2 protein in fibroblasts of one patient with biallelic loss‐of‐function variants. The data suggest that NUDCD2 deficiency causes this recognizable syndrome that has features of a ciliopathy with additional complications.