Thanatophoric dysplasia caused by double missense FGFR3 mutations.

Thanatophoric dysplasia is a lethal chondrodysplasia caused by heterozygous fibroblast growth factor receptor 3 (FGFR3) missense mutations. Mutations have been identified in several domains of the receptor. The most frequent mutations (p.

Novel mutation and atlantoaxial dislocation in two siblings from India with Dyggve-Melchior-Clausen syndrome.

Dyggve-Melchior-Clausen syndrome is a rare variety of spondyloepimetaphyseal dysplasia which often resembles Morquio syndrome. We describe two siblings from India with the condition and report a novel homozygous mutation in them (c.1172_1173insC).

Human immortalized chondrocytes carrying heterozygous FGFR3 mutations: an in vitro model to study chondrodysplasias.

Achondroplasia and thanatophoric dysplasia are human chondrodysplasias caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We have developed an immortalized human chondrocyte culture model to study the regulation of chondrocyte functions. One control and eight mutant chondrocytic lines expressing different FGFR3 heterozygous mutations were obtained.

Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

Achondroplasia (ACH) and hypochondroplasia (HCH) are two autosomal-dominant skeletal disorders caused by recurrent missense FGFR3 mutations in the transmembrane (TM) and tyrosine kinase 1 (TK1) domains of the receptor. Although 98% of ACH cases are accounted for by a single G380R substitution in the TM, a common mutation (N540K) in the TK1 region is detected in only 60-65% of HCH cases. The aim of this study was to determine whether the frequency of mutations in patients with HCH was the result of incomplete mutation screening or genetic heterogeneity.

Mutation screening in patients with syndromic craniosynostoses indicates that a limited number of recurrent FGFR2 mutations accounts for severe forms of Pfeiffer syndrome.

Crouzon Syndrome (CS), Pfeiffer syndrome (PS) and the phenotypically related Jackson-Weiss (JW) variant are three craniosynostotic conditions caused by heterozygous mutations in Fibroblast Growth Factor Receptor (FGFR) genes. Screening a large cohort of 84 patients with clinical features of CS, PS or JW by direct sequencing of genomic DNA, enabled FGFR1, 2 or 3 mutation detection in 79 cases. Mutations preferentially occurred in exons 8 and 10 of FGFR2 encoding the third Ig loop of the receptor.