Sequencing the CaSR locus in Pakistani stone formers reveals a novel loss-of-function variant atypically associated with nephrolithiasis.
BMC Med Genomics
; 14(1): 266, 2021 11 12.
Article
en En
| MEDLINE
| ID: mdl-34772415
ABSTRACT
BACKGROUND:
Nephrolithiasis (NL) affects 1 in 11 individuals worldwide and causes significant morbidity and cost. Common variants in the calcium sensing receptor gene (CaSR) have been associated with NL. Rare inactivating CaSR variants classically cause hyperparathyroidism, hypercalcemia and hypocalciuria. However, NL and familial hypercalciuria have been paradoxically associated with select inactivating CaSR variants in three kindreds from Europe and Australia.METHODS:
To discover novel NL-associated CaSR variants from a geographically distinct cohort, 57 Pakistani families presenting with pediatric onset NL were recruited. The CaSR locus was analyzed by directed or exome sequencing.RESULTS:
We detected a heterozygous and likely pathogenic splice variant (GRCh37 Chr3122000958A>G; GRCh38 Chr312228211A>G; NM_000388c.1609-2A>G) in CaSR in one family with recurrent calcium oxalate stones. This variant would be predicted to cause exon skipping and premature termination (p.Val537Metfs*49). Moreover, a splice variant of unknown significance in an alternative CaSR transcript (GRCh37 Chr3122000929G>C; GRCh38 Chr3122282082G >C NM_000388c.1609-31G >C NM_001178065c.1609-1G >C) was identified in two additional families.CONCLUSIONS:
Sequencing of the CaSR locus in Pakistani stone formers reveals a novel loss-of-function variant, expanding the connection between the CaSR locus and nephrolithiasis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cálculos Renales
/
Predisposición Genética a la Enfermedad
/
Receptores Sensibles al Calcio
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Child
/
Female
/
Humans
/
Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
BMC Med Genomics
Asunto de la revista:
GENETICA MEDICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Pakistán