Identification of novel mutations in CD2BP1 gene in clinically proven rheumatoid arthritis patients of south India

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• 作者：Bhattaram Siddhartha Kumar^a ; Pasupuleti Santhosh Kumar^b ; Nannepaga Sowgandhi^a ; Bhattaram Manoj Prajwal^a ; Alladi Mohan^a ; Kadainti Venkata Subbaraya Sarma^c ; Potukuchi Venkata Gurunadha Krishna Sarma^b ; ^{sarmasvims@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CD2BP1 ; PAPA syndrome ; Rheumatoid arthritis ; RMSD ; SH3 domain
• 刊名：European Journal of Medical Genetics
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：59
• 期：8
• 页码：404-412
• 全文大小：1202 K

文摘

Pyogenic Arthritis, Pyoderma gangrenosum, and Acne (PAPA syndrome) is a rare autosomal dominant, auto-inflammatory disease that affects joints and skin. The disease results due to mutations in the cluster of differentiation 2 binding protein 1 (CD2BP1) gene on chromosome 15q24.3. Rheumatoid arthritis (RA) is a common, genetically complex disease that affects the joints with occasional skin manifestations. Studies related to the pathophysiology of inflammation in these two disorders show a certain degree of overlap at genetic level. The present study was done to confirm the existence of such a genetic overlap between PAPA syndrome and RA in south Indian population. In the present study 100 patients who were clinically diagnosed rheumatoid arthritis and 100 apparently healthy controls were chosen and the 15 exons of CD2BP1 gene were PCR-amplified and sequenced. The sequence analysis showed that in exon 3 thirty eight patients revealed presence of novel heterozygous missense mutations p.Glu51Asp, p.Leu57Arg and p.Ala64Thr. In exons 6, 10 and 14 eight patients showed 44 novel missense mutations and two patients showed novel frame shift mutations p.(Met123_Leu416delinsThr) and p.(Thr337Profs*52) leading to truncated protein formation. Such mutations were not seen in controls. Further, the in silico analysis revealed the mutant CD2BP1 structure showed deletion of Cdc15 and SH3 domains when superimposed with the wild type CD2BP1 structure with variable RMSD values. Therefore, these structural variations in CD2BP1 gene due to the mutations could be one of the strongest reasons to demonstrate the involvement of these gene variations in the patients with rheumatoid arthritis.