A study on the role of FMR1 CGG trinucleotide repeats in Jordanian poor ovarian responders.

The expansion of trinucleotide CGG repeats in the promoter of fragile X mental retardation 1 (FMR1) gene is associated with fragile X and fragile X associated tremor/ataxia syndromes. While the expansion of CGG repeats has been associated with such neuro/psychiatric diseases, the contraction of CGG repeats has been recently suggested as an indication of ovarian dysfunction. This study aimed to evaluate a possible association of the short CGG repeats with poor ovarian responders (POR) and to test for a possible correlation between the CGG size and different known markers of the ovarian reserve, namely FSH, AMH, and the number of retrieved oocytes from Jordanian females. We found a significant difference between the CGG median allele size between the cases and the controls (p < 0.001), where poor ovarian responders had shorter CGG repeats compared to the healthy controls. Also, females with alleles <26 had twice the odds to be presented in the POR compared to the controls. However, we did not find a significant correlation between CGG sizes and the markers of ovarian reserve. We conclude that although low CGG repeats appear to be linked to POR, the clinical utility of FMR1 for predicting ovarian response needs further investigation.

Identification of a novel WFS1 homozygous nonsense mutation in Jordanian children with Wolfram syndrome.

Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder characterized by the presentation of early onset type I diabetes mellitus and optic atrophy with later onset diabetes insipidus and deafness. WFS1 gene was identified on chromosome 4p16.1 as the gene responsible for WS disease given that most of the WS patients were found to carry mutations in this gene. This study was carried out to investigate the molecular spectrum of WFS1 gene in Jordanian families. Molecular and clinical characterization was performed on five WS patients from two unrelated Jordanian families. Our data indicated that WS patients of the first family harbored two deletion mutations (V415del and F247fs) located in exon 8 and exon 7 respectively, with a compound heterozygous pattern of inheritance; while in the second family, we identified a novel nonsense mutation (W185X) located in exon 5 in the N-terminal cytoplasmic domain with a homozygous pattern of inheritance. This mutation can be considered as loss of function mutation since the resulting truncated protein lost both the transmembrane domain and the C-terminal domain. Additionally, the W185X mutation lies within the CaM binding domain in wolframin protein which is thought to have a role in the regulation of wolframin function in response to calcium levels.

Polymorphisms in NLRP1 gene and susceptibility to autoimmune thyroid disease.

The autoimmune thyroid disorders, or AITDs, comprise 2 related disorders, Graves' disease and Hashimoto thyroiditis. In AITD, immune system produces antibodies against autothyroid antigens. The etiology of AITDs involves a complex interaction between genetic predisposing factors and environmental triggering factors. Variations in NACHT leucine-rich repeat protein 1(NLRP1) gene a key regulator of the innate immunity have been shown to confer risk for vitiligo and several autoimmune diseases. In this study we hypothesize that variants in NLRP1 gene might be involved in the susceptibility to autoimmune thyroid disease. Five single nucleotide polymorphisms (SNPs) in NLRP1 were genotyped in 207 AITD patients and 220 normal controls. We found that NLRP1 rs12150220 T allele (OR = 1.273, 95% CI: 0.971-1.670, p = 0.040) and NLRP1 rs2670660 G allele (OR = 1.264, 95% CI: 0.965-1.656, p = 0.044) were significantly associated with AITD compared with controls. These results suggest that NLRP1 may be involved in the pathogenesis of AITD.