Czech dysplasia: Report of a large family and further delineation of the phenotype

• Published in: American journal of medical genetics. Part A Vol. 146A; no. 14; pp. 1859 - 1864
• Main Authors: Tzschach, Andreas, Tinschert, Sigrid, Kaminsky, Elke, Lusga, Eugen, Mundlos, Stefan, Graul‐Neumann, Luitgard M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.07.2008; Wiley-Liss
• Subjects: Adolescent; Adult; Aged; arthritis; Biological and medical sciences; Bone Diseases, Developmental - genetics; Bone Diseases, Developmental - pathology; Child; Child, Preschool; COL2A1; Collagen Type II - genetics; Czech dysplasia; Czech Republic; deafness; Diseases of the osteoarticular system; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Female; Genes, Dominant; Hearing Loss, Sensorineural - genetics; Humans; Male; Medical genetics; Medical sciences; Middle Aged; Miscellaneous. Osteoarticular involvement in other diseases; Mutation, Missense; Non tumoral diseases; Osteoarthritis; Otorhinolaryngology. Stomatology; Pedigree; Phenotype; sensorineural hearing loss; spondyloepiphyseal osteoarthritis; Syndrome; Czech Republic; sensorineural hearing loss; Dysplasia; Family study; Internal ear disease; Diseases of the osteoarticular system; Auditory disorder; Arthritis; Symptomatology; Phenotype; COL2A1; Arthropathy; Family environment; ENT disease; Perception hearing loss; Czech dysplasia; Degenerative disease; deafness; Osteoarthritis; Sensory hearing loss; spondyloepiphyseal osteoarthritis
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32389

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. © 2008 Wiley‐Liss, Inc.