title: Hereditary hypophosphatemic rickets with hypercalciuria and nephrolithiasis-identification of a novel SLC34A3/NaPi-IIc mutation.
abstract: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is characterized by rickets, hyperphosphaturia, hypophosphatemia, elevated 1,25-dihydroxyvitamin-D, increased gastrointestinal calcium absorption and hypercalciuria. Serum calcium, 25-hydroxyvitamin-D and PTH levels are normal. Here we describe a boy with HHRH, nephrolithiasis, and compound heterozygosity for one previously described mutation (g.4225_50del) and a novel splice mutation (g.1226G>A) in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. The patient's mother and grandmother are carriers of g.4225_50del, and both have a history of nephrolithiasis associated with hypercalciuria and elevated 1,25-dihydroxyvitamin-D. His three siblings (2-6 years old), who are also carriers of g.4225_50del, have hypercalciuria but so far their renal ultrasounds are normal. Thus, SLC34A3/NaPi-IIc mutations appear to be associated with variable phenotypic changes at presentation, which can include recurrent nephrolithiasis.
authors.affiliation: Department of Pediatric Endocrinology and Diabetes, Connecticut Children's Medical Center, Hartford, USA. pphulwa@ccmckids.org
authors.forename: Priya
authors.initials: P
authors.lastname: Phulwani
authors.forename: Clemens
authors.initials: C
authors.lastname: Bergwitz
authors.forename: Graciana
authors.initials: G
authors.lastname: Jaureguiberry
authors.forename: Majjid
authors.initials: M
authors.lastname: Rasoulpour
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Estrada
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D053098:Familial Hypophosphatemic Rickets / Q000150:complications* / Q000235:genetics*; D005260:Female; D006801:Humans; D053565:Hypercalciuria / Q000150:complications* / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D053040:Nephrolithiasis / Q000150:complications* / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; C493562:SLC34A3 protein, human; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc