Novel TRPV6 mutations in the spectrum of transient neonatal hyperparathyroidism.
J Physiol Sci
; 70(1): 33, 2020 Jul 09.
Article
en En
| MEDLINE
| ID: mdl-32646367
ABSTRACT
Maternal-fetal calcium (Ca2+) 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 Ca2+ 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 Ca2+ concentration could have led to Ca2+ overload and subsequent death of cells expressing this mutant channel. These results indicate that the AR6 domain contributes to TRPV6-mediated maintenance of intracellular Ca2+ concentrations, and that this region could play a novel role in regulating the activity of TRPV6 Ca2+-selective channels.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diagnóstico Prenatal
/
Canales de Calcio
/
Canales Catiónicos TRPV
/
Hiperparatiroidismo
/
Mutación
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Newborn
/
Pregnancy
Idioma:
En
Revista:
J Physiol Sci
Asunto de la revista:
FISIOLOGIA
/
TRAUMATOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón