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

ABSTRACT: 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 ?KL (?-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 parentsbiochemical 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.

SUBMITTER: Dayal D

PROVIDER: S-EPMC7882081 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Dayal Devi D Gupta Shruti S Kumar Rakesh R Srinivasan Radhika R Lorenz-Depiereux Bettina B Strom Tim M TM

Intractable & rare diseases research 20210201 1

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 ...[more]

PMID: 33614378

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Project description:Hyperphosphatemic familial tumoral calcinosis (HFTC) presents with varied neurological manifestations that have been reported in the literature like facial palsy, vision and hearing impairment, stroke, and headache. In this article, we reported a 12-year-old girl child patient with recurrent facial weakness with bilateral hearing impairment and multiple ulcerative lesions on lower limbs and elbows. On examination, she had lower motor neuron (LMN) facial palsy with conductive hearing loss. The investigations showed hyperphosphatemia (9.3 mg/dL) with normal serum calcium (10.4 mg/dL), alkaline phosphatase (147.9 U/L), parathyroid hormone (23.12 pg/mL), and renal function tests. Elevated serum calcium and phosphorus product (96.72 mg 2 /mL 2 ) and elevated renal tubular reabsorption of phosphate (TMPxGFR) value (9.16) were noted. Skeletal survey showed hyperostosis in the long bone diaphysis, vertebrae, ribs, pelvic bone, skull, and facial bones with narrowing of cranial ostium, characteristically without any peri-articular soft tissue calcifications. An angiogram showed multiple intravascular calcifications. She was managed with a low-phosphate diet, sevelamer, niacinamide, acetazolamide, sucroferric oxyhydroxide to lower serum phosphate level, and topical sodium thiosulfate ectopic cutaneous calcification. Exome sequencing showed novel homozygous inframe deletion of ACG in FGF23 gene exon 3 at c.374_376 delins position (p. Asp125del) in the proband and a mutation in the heterozygous state in the mother and elder sibling, thus confirming a molecular diagnosis of HFTC. Our case had a unique neurological presentation of recurrent bilateral lower motor nerve facial palsy, hearing loss, multiple ectopic cutaneous calcifications without peri-articular deposits, multiple intravascular, intracranial, and vertebral endplate calcification, which has not been reported earlier. The proband showed a novel pathogenic variant suggesting an expanding phenotype of HFTC.

Dataset Information

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

Publications

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

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