Affiliation:
1. Department of Medical Chemistry and Biochemistry, Medical University Sofia , Sofia , Bulgaria
2. Genetic Medico-Diagnostic Laboratory “Genica,” Sofia , Bulgaria
3. Department of Medical Genetics, University Hospital “St. George,” Plovdiv , Bulgaria
Abstract
Abstract
Here we report the first familial case spread through at least three generations, genetically verified cases of Marshall-Stickler syndrome in Bulgaria. The proband, a 2-year-old girl, has craniofacial dysplasia, ocular hypertelorism, small saddle nose with a flat bridge and midface hypoplasia. The pedigree of the proband’s family showed that her father has the same clinical manifestations of the disease. In addition, her father presented with a tall, thin stature and mild hearing loss, manifested with aging. The same dysmorphological symptoms were presented by the paternal grandfather. Both patients, the 2-year-old girl and her father, have been diagnosed to carry Marshall-Stickler syndrome. The COL2A1 gene tested negative in the family. Based on the higher percentage of mutations in the COL2A1 gene, we analyzed this gene as the first target in the family. The COL2A1 gene tested negative, and we sequenced the gene further. A novel splice site mutation c.3474+1G>A was found in intron 44. This variant is related to the clinical presentation in the patient and her father. The c.3474+1G>A mutation results in altered splicing affects at the donor splice site of intron 44, which most probably gives a nonfunctional protein. The variant affects the major triple-helical domain that represents a mutation hot-spot for the gene.
Subject
Genetics (clinical),Genetics
Reference12 articles.
1. Vallat M, Fritsch D, van Coppenolle F, Detre J, Moze M, Rasbourdin FI. Le syndrome de Stickler ou arthroophtalmopathie progressive héréditaire (Stickler’s syndrome or hereditary progressive arthro-opthalmopathy) [French]. J Fr Ophtalmol. 1985; 8(4): 301307. PMID: 4020040.
2. Stickler GB, Belau PG, Farrell FJ, Jones JD, Pugh DG, Steinberg AG, et al. Hereditary progressive arthro-ophthalmopathy. Mayo Clin Proc. 1965; 40: 433-455.
3. Herrmann J, France TD, Spranger JW, Opitz JM, Wiffler C. The Stickler syndrome (hereditary arthroophthalmopathy). Birth Defects Orig Arctic Ser. 1975; 11(2): 76-103.
4. Marshall D. Ectodermal dysplasia; report of kindred with ocular abnormalities and hearing defect. Am J Ophthalmol. 1958; 45(4 Pt 2): 143-156.
5. Shanske AL, Bogdanow A, Shprintzen RJ, Marion RW. The Marshall syndrome: Report of a new family and review of literature. Am J Med Genet. 1997; 70(1): 52-57.
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献