| Popis: |
Thanatophoric dysplasia types I and II (TD1 and TD2) are autosomal dominant lethal skeletal dysplasias TD1 is more common and is characterized by rhizomelia, platyspondyly and megalencephaly. Straight femora, taller vertebral bodies and severe cloverleaf skull characterize TD2. TD1 is caused by sporadic mutations in the fibroblast growth factor receptor 3 (FGFR3). Eight distinct FGFR3 missense mutation located in exon 7 (C742T: R248C, C746G: S249C), exon 10 (G1108T. G370C, A1111T: S371C, A1118G: Y373C), and exon 19 (T2419G: J807G, T2419A: J807R, A2421T: J807C) have been described. These mutations either create unpaired cysteine residues in the FGFR3 extracellular domain or disrupt the stop codon, leading to translation of an additional 144 ammo acids. One common FGFR3 mutation has been found in all patients with TD2 (A1948G. K650E). This mutation is within the intracellular tyrosine kinase domain of the FGFR3 gene. We report here the results of mutation analysis of FGFR3 exons 7, 10, and 19 in 76 patient samples referred to our laboratory to rule out TD1 and TD2. Clinical information was derived from ultrasound studies, X-rays, and/or obtained at autopsy and ranged from short limbs to a classical description of TD1 or TD2. Genomic DNA was isolated from a variety of tissues including amniotic fluid cells (direct and tissue culture), chorionic villus cells (direct and tissue culture) and fetal tissues (frozen tissue or tissue culture) and analyzed by PCR amplification followed by either restriction enzyme analysis or allele specific oligonucleotide analysis. An identifiable mutation was found in 56.6% of samples analyzed (43). Eight patients were found to have the A1948G. K650E TD2 mutation. Thirty-five patients had TD 1 mutations. The C742T: R248C mutation was found most frequently (20 patients), followed by the A118G: Y373C (8 patients). Four patients possessed the C746G:S249C mutation and 2 patients possessed mutations in the exon 19 stop codon. Test results are available approximately 7 days from receipt of the sample in the laboratory. Information provided by DNA analysis of the FGFR3 gene provides important information to patients. |
