Case report: compound heterozygous PTH1R variant(s) in a patient with inactivating PTH/PTHrP signalling disorder type 1 (iPPSD1).
Abhishek Kulkarni, Devika Desai, Joewin Monteiro
✦ AI-curated · Sources linked
Case in brief
A 9-year-old girl from the Indian subcontinent presented with primary failure of tooth eruption, dental anomalies, valgus deformity, PTH resistance, and subclinical hypothyroidism. Whole-exome sequencing identified two novel PTH1R variants, c.557G>A (p.Arg186His) and c.686delC (p.Phe230fs*6), in exons 8 and 9. Sanger sequencing confirmed that the variants were in trans; they were absent from major population databases. The findings established inactivating PTH/PTHrP signalling disorder type 1 (iPPSD1). Early molecular diagnosis supported multidisciplinary management.
What made this case unusual
The patient had compound heterozygous PTH1R variants, an exceptionally rare genotype associated with severe phenotypes; the report describes the first such case in the Indian population.
Diagnostic / clinical pearl
In a child with primary failure of tooth eruption and skeletal or endocrine findings, consider iPPSD1; molecular testing can confirm PTH1R-related disease and clarify variant phase.