抽象的

Genotyping and clinical characteristics screening of children with intellectual disability in Western India

Yashvant Khimsuriya, Nikhil Kharod, Jenabhai Chauhan

Background: The RhoGTPases (ARHGEF6, OPHN1 and PAK3) are key signaling proteins, and can inter-relate extracellular and intracellular signals to sort out changes in the actin cytoskeleton of neuronal network connectivity. IL1RAPL2 is a member of Interleukin 1 receptor family that is expressed at high level in post-natal brain structures involved in the hippocampal memory system. The mutations of these genes have been reported to cause intellectual disability (ID). Therefore, this study is conducted to scrutinize distinctive distributions of genomic variations on West Indian population.

Subjects and Methods: The genotyping for determination of SNPs associated with X-linked genes (rs35747426 in ARHGEF6, rs121434612 in PAK3, rs199985543 in OPHN1 and rs9887672 in IL1RAPL2) was performed in phenotypically screened 116 intellectually disabled and 100 healthy children by PCRRFLP method.

Results: It has identified that allelic frequencies for rs199985543 and rs9887672 are seen progressively present in the disease group, indicating a significant level of association with ID in Gujarat population. The multifactor dimensionality reduction (MDR), SNP-SNP genotype models are resulted with a relationship of ID if there should be an occurrence of the OPHN1 and IL1RAPL2 gene variants. Additionally, rs199985543 was analyzed for OPHN1 protein structure and stability prediction, which results damaging effect to the protein. Surprisingly, no variation was found for rs35747426 ARHGEF6 and rs121434612 PAK3 polymorphisms in the present study population.

Conclusion: This phenotype-genotype relationship has a solid and measurable connection according to the carrier genotypes of the variations and different types of ID, that confirm the mutation in OPHN1 and IL1RAPL2 genes permit serious attention for disease risk.