A novel homozygous variant in exon 10 of the GALNT3 gene causing hyperphosphatemic familial tumoral calcinosis in a family from North India

• Published in: Intractable & Rare Diseases Research 2021/02/28, Vol.10(1), pp.55-57
• Main Authors: Dayal, Devi, Gupta, Shruti, Kumar, Rakesh, Srinivasan, Radhika, Lorenz-Depiereux, Bettina, Strom, Tim M
• Format: Article
• Language: English
• Subjects: calcinosis cutis; GALNT3 gene; hyperphosphatemic familial tumoral calcinosis; Indian family; Letter; novel variant
• ISSN: 2186-3644; 2186-361X
• DOI: 10.5582/irdr.2020.03084

Hyperphosphatemic familial tumoral calcinosis (HFTC) is an extremely rare autosomal recessive disorder caused by variants in the GALNT3 (N-acetylgalactosaminyltransferase 3), FGF23 (Fibroblast Growth Factor-23) and αKL (α-Klotho) genes, which results in progressive calcification of soft tissues. We describe the case of a 9-year-old girl who presented with recurrent hard nodular swellings on her feet and knees which intermittently discharged chalky white material. Her younger brother also had a similar condition. Both siblings showed hyperphosphatemia, but the parents’ biochemical parameters were normal. The histological features of the material aspirated from a skin lesion were consistent with tumoral calcinosis. Sanger sequencing identified a novel homozygous non-synonymous sequence variant in exon 10 of the GALNT3 gene (NM_004482.3:c.[1681T>A];[1681T>A], NP_004473.2:p. [Cys561Ser];[Cys561Ser] in the proband and her affected brother. The parents were heterozygous carriers for the same sequence variant. In conclusion, we report a new variant in the GALNT3 gene that caused HFTC in a North Indian family.