Abstract:

Objective To analyze the characteristic of molecular genetics and clinical manifestations in 2 families with osteogenesis imperfecta (OI). Design Retrospective case serie. Participants 2 Chinese OI families from Sichuan and Guangdong provinces, one of these we had reported in <Genetics & Molecular Research> and was followed up for five years in this study. Methods The families members received clinical examinations to evaluate ocular and skeleton conditions. Peripheral blood samples were collected and the DNA was extracted for pathogenic mutations identification. Main Outcome Measure Medical history, visual acuity, central corneal thickness (CCT), anterior and posterior segment examination, hearing, X-ray inspection and gene sequencing. Results These two OI families were respectively diagnosed with type Ⅰ and type Ⅳ OI, both following an autosomal-dominant pattern of inheritance and sharing same clinical findings including blue sclera, corneal thinning, recurrent fracture, hearing loss and spinal deformity, but short stature, dentinogenesis imperfecta and worse skeletal deformity were only found in family 2. Results of gene sequencing revealed a novel deletion we had reported (c.2329delG, p.Ala777Profs*330) in exon 33 of COL1A1 gene in family 1 causing a frameshift alteration after codon 777 leading to a truncated protein, and a novel heterozygous point mutation (c.725G>T, p.Gly242Val) in family 2. Conclusion Our findings identified 2 novel mutations (c.2329delG, c.725G>T) in the COL1A1 gene, which were associated with pathogenesis of OI in these 2 Chinese families. (Ophthalmol CHN, 2019, 28: 273-279)
 

Key words: osteogenesis imperfecta, COL1A1, collagen type 1, molecular genetics