5528
Ahmed Khairy Taha saad
Mutation Analysis Of FKBPLO And
SERPINFI Genes In Autosomal Recessive
Osteogenesis Imperfecta Patients
Osteogenesis Imperfecta , SERpINFI, FKBplO
Osteogenesis imperfecta (OI) is a clinically heterogeneous heritable connective tissue disorder charactenzed by recurrent fragile fractures of bones. About 90% of OI cases are of autosomal dominant forms, caused by mutations in COLtAI and COLIA2 genes. Recessive OI forms are caused by mutations in collagen modification-related genes. Recessive forms incidence of OI is increasing u*irg Egyptians due to high consanguinity rate. Mutations in SERqINFI andifyptO genes cause autosomal recessive OI types VI and XI respectively. Our aim was to identify pathogenic mutations within those two g.n. u-bng Egyptian oI patients. Phenotypic features of OI patients were invesiigated Uy "vaiuiting X-iays and bone mineral density. Fighteen patients with m;derate-to-severe b-one fragility, significant low bone mineral density, and severe deformities were recruited from 18 unrelated families for this study after obtaining informed consent forms. We performed sanger sequencing for all exons of the two genes. Two homozygous pathogenic mutations in SERpINFI gene were identifiid; a novel homozy[ous 37-bp deletion in exon 8 (c.t2t7_1253det37. p.L406pfsX6), which tedio a truncated protein, and a known homozygous nonsense mutation in exon 6 (c-651G>A, p-W2l7X) that was detected in three patients from 3 unrelated tamilies. Moreover, two novel heterozygous variants in exon 5 and exon g of SERPINFl gene respectively. Also, three novel heterozygous missense variants rvere defined in exons 1 and 2 of FKBp1O gene. siuay for more cases is recommended to better know the frequency of these 2 genes imong the expanding list of AR-OI genes in addition to target panel r.qr"rrdog to reveal the mutational spectrum among Egyptian patients.
2019
M.Sc
Cairo
Science