Open AccessFGFR3 mutation frequency in 324 cases from the International Skeletal Dysplasia Registry
Author(s) -
Xue Yuan,
Sun Angela,
Mekikian P. Betty,
Martin Jorge,
Rimoin David L.,
Lachman Ralph S.,
Wilcox William R.
Publication year - 2014
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.96
Subject(s) - medicine , mutation , dysplasia , genetics , bioinformatics , pathology , pediatrics , biology , gene
Fibroblast growth factor receptor 3 ( FGFR 3 ) is the only gene known to cause achondroplasia ( ACH ), hypochondroplasia ( HCH ), and thanatophoric dysplasia types I and II ( TD I and TD II). A second, as yet unidentified, gene also causes HCH . In this study, we used sequencing analysis to determine the frequency of FGFR 3 mutations for each phenotype in 324 cases from the International Skeletal Dysplasia Registry ( ISDR ). Our data suggest that there is a considerable overlap of genotype and phenotype between ACH and HCH . Thus, it is important to test for mutations found in either disorder when ACH or HCH is suspected. Only two of 29 cases with HCH did not have an identified mutation in FGFR 3 , much less than previously reported. We recommend testing other mutations in FGFR 3 , instead of just the common HCH mutation, p.Asn540Lys. The mutation frequency for TD I and TD II in the largest series of cases to date are also reported. This study provides valuable information on FGFR 3 mutation frequency of four skeletal dysplasias for clinical diagnostic laboratories and clinicians.