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Genetic analysis of osteogenesis imperfecta in the Palestinian population : molecular screening of 49 affected families

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Abstract
Background : 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 COL1A1, five in COL1A2, three in BMP1, three in FKBP10, two in TMEM38B, two in P3H1, and one each in CRTAP, SERPINF1, and SERPINH1. 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 TMEM38B 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.
Keywords
Autosomal dominant, autosomal recessive, next-generation sequencing, osteogenesis imperfecta, COLLAGEN MUTATION DATABASE, I COLLAGEN, BONE FRAGILITY, SKELETAL DYSPLASIAS, LEPRE1 MUTATIONS, RECESSIVE FORMS, BMP1 MUTATIONS, BRUCK SYNDROME, SERPINF1, IDENTIFICATION

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Chicago
Essawi, Osama, Sofie Symoens, Maha Fannana, Mohammad Darwish, Mohammad Farraj, Andy Willaert, Tamer Essawi, et al. 2018. “Genetic Analysis of Osteogenesis Imperfecta in the Palestinian Population : Molecular Screening of 49 Affected Families.” Molecular Genetics & Genomic Medicine 6 (1): 15–26.
APA
Essawi, O., Symoens, S., Fannana, M., Darwish, M., Farraj, M., Willaert, A., Essawi, T., et al. (2018). Genetic analysis of osteogenesis imperfecta in the Palestinian population : molecular screening of 49 affected families. MOLECULAR GENETICS & GENOMIC MEDICINE, 6(1), 15–26.
Vancouver
1.
Essawi O, Symoens S, Fannana M, Darwish M, Farraj M, Willaert A, et al. Genetic analysis of osteogenesis imperfecta in the Palestinian population : molecular screening of 49 affected families. MOLECULAR GENETICS & GENOMIC MEDICINE. 2018;6(1):15–26.
MLA
Essawi, Osama, Sofie Symoens, Maha Fannana, et al. “Genetic Analysis of Osteogenesis Imperfecta in the Palestinian Population : Molecular Screening of 49 Affected Families.” MOLECULAR GENETICS & GENOMIC MEDICINE 6.1 (2018): 15–26. Print.
@article{8551674,
  abstract     = {Background : 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 COL1A1, five in COL1A2, three in BMP1, three in FKBP10, two in TMEM38B, two in P3H1, and one each in CRTAP, SERPINF1, and SERPINH1. 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 TMEM38B 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.},
  author       = {Essawi, Osama and Symoens, Sofie and Fannana, Maha and Darwish, Mohammad and Farraj, Mohammad and Willaert, Andy and Essawi, Tamer and Callewaert, Bert and De Paepe, Anne and Malfait, Fransiska and Coucke, Paul},
  issn         = {2324-9269},
  journal      = {MOLECULAR GENETICS \& GENOMIC MEDICINE},
  language     = {eng},
  number       = {1},
  pages        = {15--26},
  title        = {Genetic analysis of osteogenesis imperfecta in the Palestinian population : molecular screening of 49 affected families},
  url          = {http://dx.doi.org/10.1002/mgg3.331},
  volume       = {6},
  year         = {2018},
}

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