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.