Czech dysplasia: report of a large family and further delineation of the phenotype.
Czech dysplasia (OMIM 609162) is a recently delineated COL2A1 disorder characterized by early-onset progressive pseudorheumatoid arthritis, platyspondyly, short third and fourth metatarsals, normal height, and the absence of ophthalmological problems or cleft palate. Czech dysplasia is caused by a specific missense mutation (R275C, c.823C > T) in the triple helical domain of the COL2A1 gene. We report on a large family with 11 patients with typical Czech dysplasia and sensorineural hearing loss. Hearing loss has hitherto not been considered as a major manifestation of Czech dysplasia. Mutation analysis documented the COL2A1 c.823C > T (R275C) mutation in all affected individuals. Thus, Czech dysplasia is possibly caused exclusively by the R275C mutation, which is a unique situation among the COL2A1 disorders. The family provides further evidence for the remarkably uniform manifestation of the clinical and radiological abnormalities and adds hearing loss to the list of major anomalies of Czech dysplasia.
Tzschach
Andreas
A
Institute of Medical Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany. tzschach@molgen.mpg.de
Tinschert
Sigrid
S
Kaminsky
Elke
E
Lusga
Eugen
E
Mundlos
Stefan
S
Graul-Neumann
Luitgard M
LM
D000293:Adolescent; D000328:Adult; D000368:Aged; D001848:Bone Diseases, Developmental / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D024043:Collagen Type II / Q000235:genetics*; D018153:Czech Republic; D005260:Female; D005799:Genes, Dominant; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome
C499177:COL2A1 protein, human; D024043:Collagen Type II