SLC34A3 intronic deletion in a new kindred with hereditary hypophosphatemic rickets with hypercalciuria.
OBJECTIVE
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an autosomal recessive form of hypophosphatemia with hyperphosphaturia, hypercalciuria, and hypercalcemia. In two reports on six affected kindreds with HHRH, the disease was mapped to chromosome 9q34, which contains the SLC34A3 gene that encodes the renal type 2c sodium-phosphate cotransporter. Our objective was to define the clinical course of these cases in a family with HHRH and to screen for SLC34A3 gene in order to determine whether these mutations are responsible for HHRH.


METHODS
After clinical and biochemical evaluations, the entire SLC34A3 gene was screened using PCR amplification followed by direct sequencing technique. In this paper, we describe a new kindred with HHRH and a case of progressive and complicated HHRH presenting at age 27 years.


RESULTS
We found 101-bp deletion in intron 9 of the SLC34A3 gene. The index patient was homozygous for this mutation which has been previously reported in a Caucasian population. This is the first report for presence of SLC34A3 intron 9 deletion in an Iranian population.


CONCLUSIONS
These data showed that HHRH can be easily missed or underdiagnosed. Genetic evaluation of patients with familial hypercalciuria, hypophosphatemia and nephrolithiasis is needed for further information on the prevalence and management of this rare disorder.
Tehran University of Medical Sciences, Endocrinology and Metabolism Research Institute, Tehran, Iran. shirinhasanir@yahoo.com
Shirin
S
Hasani-Ranjbar
Mahsa M
MM
Amoli
Azadeh
A
Ebrahim-Habibi
Ehsan
E
Dehghan
Akbar
A
Soltani
Parvin
P
Amiri
Bagher
B
Larijani
D000328:Adult; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D053098:Familial Hypophosphatemic Rickets / Q000150:complications / Q000235:genetics*; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D053565:Hypercalciuria / Q000150:complications / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc / Q000235:genetics*
C493562:SLC34A3 protein, human; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc