Novel TRPV6 mutations in the spectrum of transient neonatal hyperparathyroidism

• Published in: The journal of physiological sciences Vol. 70; no. 1; p. 33
• Main Authors: Suzuki, Yoshiro, Sawada, Hirotake, Tokumasu, Tomoko, Suzuki, Shigeru, Ninomiya, Shinsuke, Shirai, Masaru, Mukai, Tokuo, Saito, Claire T, Nishimura, Gen, Tominaga, Makoto
• Format: Journal Article
• Language: English
• Published: Japan Springer 09.07.2020; BioMed Central
• Subjects: Adult; Ankyrins; Birth weight; Bone density; Calcium (intracellular); Calcium - metabolism; Calcium channels; Calcium Channels - genetics; Calcium Channels - metabolism; Calcium transport; Cell death; Cloning; Families & family life; Female; Fetus - diagnostic imaging; Fetuses; Genetic aspects; Glucose; Humans; Hyperparathyroidism; Hyperparathyroidism - diagnosis; Hyperparathyroidism - genetics; Hyperparathyroidism - metabolism; Infant, Newborn; Infants (Newborn); Intracellular; Male; Membrane trafficking; Mineralization; Mutagenesis; Mutation; Neonates; Original Paper; Parathyroid hormone; Placenta; Pregnancy; Prenatal Diagnosis - methods; Thorax; Transient receptor potential proteins; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; Ultrasonic imaging; Ventilators; Vitamin D; Vitamin deficiency; Japan; United States > US; Maternal–fetal calcium transport; Membrane trafficking; Patch-clamp recording; Transient neonatal hyperparathyroidism (TNHP); Transient receptor potential channel (TRP channel)
• ISSN: 1880-6546; 1880-6562
• DOI: 10.1186/s12576-020-00761-2

Maternal-fetal calcium (Ca ) transport in the placenta plays a critical role in maintaining fetal bone mineralization. Mutations in the gene encoding the transient receptor potential cation channel, subfamily V, member 6 (TRPV6) have been identified as causative mutations of transient neonatal hyperparathyroidism due to insufficient maternal-fetal Ca transport in the placenta. In this study, we found two novel mutations in subjects that have transient neonatal hyperparathyroidism. TRPV6 carrying the mutation p.Arg390His that localizes to the outer edge of the first transmembrane domain (S1) showed impaired trafficking to the plasma membrane, whereas TRPV6 having the mutation p.Gly291Ser in the sixth ankyrin repeat (AR) domain had channel properties that were comparable those of WT channels, although the increases in steady-state intracellular Ca concentration could have led to Ca overload and subsequent death of cells expressing this mutant channel. These results indicate that the AR6 domain contributes to TRPV6-mediated maintenance of intracellular Ca concentrations, and that this region could play a novel role in regulating the activity of TRPV6 Ca -selective channels.