Association of polymorphism (RS1800896) of IL-10 gene and IL-10 gene expression in ovarian cancer patients from Georgia

Background/Aim: Ovarian cancer is one of the most important causes of tumour-associated mortality and morbidity in women. Some genetic alterations, determining predisposition to ovarian cancer have already been identified, but these are mostly syndrome-associated cases, most ovarian tumours are still regarded as sporadic. The aim of this research was to identify new predisposing factors that might increase ovarian cancer risk. Genetic variants of IL-10 gene in patients with ovarian cancer was analysed. Methods: Forty-eight patients with ovarian cancer along with 48 agematched controls were included in the study. Single nucleotide polymorphism (SNP) genotyping and gene expression assays for IL-10 were performed using TaqMan assay (Thermo Scientific, USA). The selected SNP was rs1800896 upstream of IL-10 gene (IL-10-1082). All statistical analyses were performed by GraphPad Prism 9.3.1 for Mac. Results: The genotype distributions of IL-10 gene polymorphisms among cancer and control groups were all according to the expected Hardy-Weinberg equilibrium. There was no statistically significant difference in frequency of genotypes and alleles between the two study groups (p > 0.05). In another analysis, the samples were grouped according to the polymorphic variant IL-10 (-1082) A/G. Subjects having the homozygous variant (A/A) had lower IL-10 mRNA levels than those with the homozygous wild (G/G) genotype in both, ovarian cancer patients and controls, p < 0.05. mRNA levels on IL-10 were different among cases and controls (p < 0.05). Patients with ovarian cancer had higher level of mRNA for IL-10. Conclusions: These results support the theory that IL-10 gene expression levels differ in patients with and without ovarian cancer. Polymorphic variant IL-10 (-1082) A/G couldn't be confirmed to explain this difference in gene expression levels

Analysis of C9orf72 repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS) [version 2; peer review: 2 approved]

Background Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder that affects the upper and lower motor neurons. Several genetic risk factors have been identified in the past decade with a hexanucleotide repeat expansion in the C9orf72 gene being the most significant. However, the presence of C9orf72 repeat expansion has not been examined in the Transcaucasian region, therefore we aimed to analyse its frequency in Georgian patients with ALS. Methods We included 64 self-reported Georgian patients with ALS from different parts of the country, fulfilling the Gold Coast criteria. To investigate the presence of an expanded GGGGCC hexanucleotide repeat in the non-coding region of the C9orf72 gene, we performed Repeat-Primed PCR (RP-PCR). Results In total, 62 sporadic and two familial ALS cases were identified. Patients were aged 26 to 84 years with a mean age of 58.3 years at disease onset. Bulbar onset was observed in 21.88%, upper limb onset in 34.38%, and lower limb onset in 43.75% of the patients. Frontotemporal dementia (FTD) fulfilling the Strong criteria was diagnosed in seven patients (10.94%). C9orf72 repeat expansion was detected in only one case using RP-PCR; the patient had a family history of dementia. Conclusions Our results indicate that C9orf72 hexanucleotide expansion does not belong to the major genetic risk factor of ALS in Georgian patients. Further genetic studies in a bigger study population are needed to reveal the genetic causes of ALS in the Transcaucasian population

First case report of Nager syndrome patient from Georgia

Nager syndrome (MIM #154400) is a rare acrofacial dysostosis syndrome predominantly characterized by malformations in craniofacial and preaxial limb bones. Most cases are sporadic and present with significant clinical heterogeneity. Although autosomal recessive and autosomal dominant modes of inheritance have been reported, most cases of Nager syndrome are spontaneous. Heterozygous variants in SF3B4 on chromosome 1q21 are found in approximately 60% of patients. Here, we report a first patient from Georgia diagnosed with Nager syndrome with detailed description of its clinical manifestations and diagnosis

Genotype-phenotype correlations of cystic fibrosis in siblings compound heterozygotes for rare variant combinations: Review of literature and case report

Here, we describe a cystic fibrosis (CF) family with affected siblings, two of whom have a combination of I1234V and 1677delTA variants with classic CF features, the third child with a combination of I1234V and L997F variants with atypical CF, and the apparently healthy mother with a combination of 1677delTA and L997F alleles. Interestingly, the sibling with I1234V and L997F variants had normal sweat test results and had a much milder phenotype than the other two siblings with I1234V and 1677delTA variants, suggesting that this combination is causative for atypical CF. The fact that their mother with the combination of 1677delTA and L997F appears to be healthy suggests that the L997F variant causes different phenotypes in different allele combinations. The current cases show that there is a genotype-phenotype correlation in this disease and underline the importance of genotyping individuals with suspected CF to allow prediction of disease severity and effective treatment