title: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: variable phenotypic expression in three affected sisters from Mexican ancestry.
abstract: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal disease caused by mutations in genes for the tight junction transmembrane proteins Claudin-16 (CLDN16) and Claudin-19 (CLDN19). We present the first case report of a Mexican family with three affected sisters carrying a p.Gly20Asp mutation in CLDN19 whose heterozygous mother showed evident hypercalciuria and normal low magnesemia without any other clinical, laboratory, and radiological symptoms of renal disease making of her an unsuitable donor. The affected sisters showed variable phenotypic expression including age of first symptoms, renal urinary tract infections, nephrolithiasis, nephrocalcinosis, and eye symptoms consisting in retinochoroiditis, strabismus, macular scars, bilateral anisocoria, and severe myopia and astigmatism. End stage renal disease due to renal failure needed kidney transplantation in the three of them. Interesting findings were a heterozygous mother with asymptomatic hypercalciuria warning on the need of carefully explore clinical, laboratory, kidney ultrasonograpy, and mutation status in first degree asymptomatic relatives to avoid inappropriate kidney donors; an evident variable phenotypic expression among patients; the identification of a mutation almost confined to Spanish cases and a 3.5 Mb block of genomic homozygosis strongly suggesting a common remote parental ancestor for the gene mutation reported.
authors.affiliation: Department of Genetics, National Institute of Medical Sciences and Nutrition "Salvador Zubirán" , México City , México .
authors.forename: María E
authors.initials: ME
authors.lastname: Arteaga
authors.forename: Walter
authors.initials: W
authors.lastname: Hunziker
authors.forename: Audrey S M
authors.initials: AS
authors.lastname: Teo
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
authors.forename: Osvaldo M
authors.initials: OM
authors.lastname: Mutchinick
mesh_terms: D000328:Adult; D057167:Claudins / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D053565:Hypercalciuria / Q000150:complications / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000601:surgery; D016030:Kidney Transplantation; D008800:Mexico; D008875:Middle Aged; D009154:Mutation; D009397:Nephrocalcinosis / Q000150:complications / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D015499:Renal Tubular Transport, Inborn Errors / Q000150:complications / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology
chemical_list: C508912:CLDN19 protein, human; D057167:Claudins
keywords: CLDN19 mutation; FHHNC; variable phenotypic expression