In:
Molecular Genetics & Genomic Medicine, Wiley, Vol. 6, No. 1 ( 2018-01), p. 15-26
Abstract:
Osteogenesis imperfecta ( OI ) is a heterogeneous hereditary connective tissue disorder clinically hallmarked by increased susceptibility to bone fractures. Methods We analyzed a cohort of 77 diagnosed OI patients from 49 unrelated Palestinian families. Next‐generation sequencing technology was used to screen a panel of known OI genes. Results In 41 probands, we identified 28 different disease‐causing variants of 9 different known OI genes. Eleven of the variants are novel. Ten of the 28 variants are located in COL 1A1 , five in COL 1A2 , three in BMP 1 , three in FKBP 10 , two in TMEM 38B , two in P3H1 , and one each in CRTAP , SERPINF 1 , and SERPINH 1 . The absence of disease‐causing variants in the remaining eight probands suggests further genetic heterogeneity in OI . In general, most OI patients (90%) harbor mainly variants in type I collagen resulting in an autosomal dominant inheritance pattern. However, in our cohort almost 61% (25/41) were affected with autosomal recessive OI . Moreover, we document a 21‐kb genomic deletion in the TMEM 38B gene identified in 29% (12/41) of the tested probands, making it the most frequent OI ‐causing variant in the Palestinian population. Conclusion This is the first genetic screening of an OI cohort from the Palestinian population. Our data are important for genetic counseling of OI patients and families in highly consanguineous populations.
Type of Medium:
Online Resource
ISSN:
2324-9269
,
2324-9269
DOI:
10.1002/mgg3.2018.6.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2734884-2
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