haniyeh rahbar kafshboran

 The CSF1R gene encodes the receptor for colony-stimulating factor-1, the macrophage, and monocyte-specific growth factor. Mutations in this gene cause hereditary diffuse leukoencephalopathy with spheroids (HDLS) with autosomal dominant inheritance and BANDDOS (Brain Abnormalities, Neurodegeneration, and Dysosteosclerosis) with autosomal recessive inheritance.

 Targeted gene sequencing was performed on the genomic DNA samples of the deceased patient and a fetus along with ten healthy members of his family to identify the disease-causing mutation. Bioinformatics tools were used to study the mutation effect on protein function and structure. To predict the effect of the mutation on the protein, various bioinformatics tools were applied.

 A novel homozygous variant was identified in the gene CSF1R, c.2498C>T; p.T833M in exon 19, in the index patient and the fetus. Furthermore, some family members were heterozygous for this variant, while they had not any symptoms of the disease. In silico analysis indicated this variant has a detrimental effect on CSF1R. It is conserved among humans and other similar species. The variant is located within the functionally essential PTK domain of the receptor. However, no structural damage was introduced by this substitution.

 In conclusion, regarding the inheritance pattern in the family and clinical manifestations in the index patient, we propose that the mentioned variant in the CSF1R gene may cause BANDDOS.

Inflammatory bowel disease (IBD) is a chronic, relapsing, inflammatory disorder of the gastrointestinal tract that includes two entities, Crohn’s disease (CD) and ulcerative colitis (UC). As with other complex diseases, both genetic susceptibility and environmental factors play role in the pathogenesis of these diseases.The tumor necrosis factor α (TNF-α) gene is located in the IBD3 region on chromosome 6p21 which is a good functional candidate for involvement in susceptibility to IBD. In addition, the promoter region of TNF-α contains various polymorphisms that have shown a significant association with IBD. In this case control study we investigated the TNF-α -857 polymorphism in 109 patients (89 UC and 16 CD) who suffered from IBD and 100 healthy age, sex and ethnicity matched adults selected from the same population, as the control group. The polymorphism was checked by amplification refractory system (ARMS) and polymerase chain reaction (PCR). Investigation of the association of TNF-α -857 gene promoter polymorphism with both types of IBD showed no significant difference in genotype and allele frequencies of this polymorphism between UC patients and controls. However, a possible association of TNF-α -857 polymorphism (p=0.03) was identified with CD. TNF-α -857 polymorphism may have a role in the development of CD in the Iranian Azeri Turkish population.