Mutational analysis of PHEX, FGF23 and DMP1 in a cohort of patients with hypophosphatemic rickets.
BACKGROUND
X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets and autosomal recessive hypophosphatemic rickets make up a group of renal phosphate wasting disorders with common clinical and biochemical characteristics. These three types of rickets are related to mutations in PHEX, FGF23 and dentin matrix protein 1 (DMP1), respectively.


OBJECTIVE
The objective of the study was to evaluate the frequency of mutations that occur in these three genes associated with hypophosphatemic rickets.


METHODS
In this study, we sequenced these genes in 76 members of 46 kindreds from a large hypophosphatemic rickets cohort.


RESULTS
Forty-two individuals from 27 kindreds were found to have mutations in PHEX; 16 of which were novel. One subject had an FGF23 mutation. No individuals were found to have mutations in DMP1 consistent with the presence of recessive hypophosphatemic rickets.


CONCLUSIONS
Our data highlight the wide spectrum of genetic variation that can be seen in PHEX, FGF23 and DMP1 when screening a large cohort with hypophosphatemic rickets.
Department of Medicine, University of Texas Health Science Center at Houston, TX 77030, USA. mary.ruppe@uth.tmc.edu
Mary D
MD
Ruppe
Patrick G
PG
Brosnan
Kit Sing
KS
Au
Phong X
PX
Tran
Barbara W
BW
Dominguez
Hope
H
Northrup
D015331:Cohort Studies; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D053098:Familial Hypophosphatemic Rickets / Q000175:diagnosis / Q000235:genetics*; D005192:Family Health; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics*; D040181:Genetic Diseases, X-Linked; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
C513309:DMP1 protein, human; D016326:Extracellular Matrix Proteins; C000717427:FGF23 protein, human; D010750:Phosphoproteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human