Novel TRPV6 variant linked with transient neonatal hyperparathyroidism

Hereditary transient neonatal hyperparathyroidism (TNHP) is a rare autosomal-recessive condition caused by variants in TRPV6 gene which encodes for a transient maternal–fetal calcium transport channel. This is characterized by interference with placental maternal–fetal calcium transport causing fetal calcium deficiency. It primarily manifests as defective bone mineralization, narrow and bell-shaped thorax, bone fractures and short bones at birth. The current study aimed to describe a novel TRPV6 variant linked with TNHP in an Indian family and the review of literature. The proband is a term female neonate with fetal growth restriction born to a third-degree consanguineous couple. She was noted to have diffuse defective bone mineralization, narrow and bell-shaped thoracic cavity, short bones and curved ribs without any bone fractures. The first pregnancy was affected with similar features in the fetus and had been terminated. Parental whole-exome sequencing suggested heterozygous missense variant in exon 12 of the TRPV6 gene (c.1585G > A, p.Asp529Asn) in both the parents. The proband required non-invasive respiratory support for ten days in neonatal intensive care unit. She had low calcium and high parathyroid hormone (PTH) and alkaline phosphatase (ALP) levels. She received calcium, phosphorus and vitamin D supplements for three months leading to normalization of serum PTH and ALP levels. Whole-exome sequencing of the proband suggested a homozygous missense variant in exon 12 of the TRPV6 gene (p.Asp529Asn; ENST00000359396.9) that results in the amino acid substitution of asparagine for aspartic acid at codon 529. To the best of author’s knowledge, this is the twelfth case of TNHP reported in literature. The novel variant of TRPV6 gene present in this family has not been reported earlier. Our finding broadens the genotypic spectrum of TNHP.