Background: Hutchinson-Gilford progeria syndrome is a rare genetic disorder characterized by dramatic premature senescence. Progeria is almost always caused by de novo point mutations in the LMNA gene that activates a cryptic splice donor site, producing a truncated mutant protein termed ‘‘progerin.’’ A previous study has also reported an association of 594 C>T mutation in B4GALT1 gene with HGPS. In this study we investigated two HGPS siblings originating from South Indian region of Andhra Pradesh. Methods: 50 healthy controls from the same ethnic group were also included in the study. Clinical characteristics of the affected children were noted down. All the exons of LMNA gene were amplified by PCR and the mutations detected by sequencing the PCR products. The 594 C>T mutation in B4GALT1 gene was also evaluated by sequencing the PCR products. Results: A novel de novo point mutation C1699T was observed in exon 10 of LMNA gene in proband as well as the affected younger sibling. However, neither the parents nor the controls had this mutation. Conclusions: The observation of heterozygous de novo LMNA mutation C1699T in HGPS patients in exon 10, supports the prevailing hypothesis that HGPS essentially represents a sporadic autosomal dominant disorder.

A comparative study of polymorphic variants of chromosomal Q-heterochromatin regions (Q-HRs) was performed in three ethnic groups (Kazakhs, Russians, and Uyghurs) of Kazakhstan. The number of chromosomal Q-HRs in the genome of studied individuals ranged from 0 to 7, with the mean 3.51, 3.51 and 4.15 in Kazakhs, Russians, and Uyghurs, respectively. The studied Kazakhs and Russians showed statistically significant homogeneity in the distribution of the number and mean number of Q-HRs, while the highest amount of chromosomal Q-HRs revealed in the Uyghur group. Differences and homogeneity between these three groups in the amount of Q-HRs in their genome are discussed as evidence in favor of the hypothesis of the possible selective value of chromosomal Q-heterochromatin material in human adaptation to various climate-geographic conditions.

Background: Cystic fibrosis (CF) is an autosomal disease with characteristics of a complex disease. Understanding ADRA2A polymorphisms are important to elucidate clinical variability that is encountered in inflammatory diseases including CF, for which diabetes is an important comorbidity beyond the primary inflammatory pulmonary disease. Method: We included 176 CF patients. The rs553668 and rs10885122 ADRA2A gene polymorphisms were screened by ARMS-PCR. A genotypic comparison was performed with 27 CF clinical variables and CFTR mutations. Results: Clinical associations were found with the categorical variables: race [rs553668 polymorphism without taking the CFTR gene into account (p= 0.002); haplotype group, without taking the CFTR gene into account (p= 0.014)], meconium ileus [rs553668 polymorphism without taking the CFTR gene into account (p= 0.030) and patients with two CFTR mutations (p= 0.0012)] and BMI [rs553668 polymorphism in patients with two CFTR mutations (p= 0.014)]. The association with numerical data was positive for age of diagnosis [rs553668 polymorphism without taking CFTR mutations into account (p= 0.022)]; the Bhalla score [rs553668 polymorphism in patients with two CFTR mutations (p= 0.014)]; and the Shwachman-Kulczycki score [rs553668 polymorphism (p= 0.008) and haplotype (p= 0.050) in patients with two CFTR mutations]. Conclusion: The rs553668 and rs10885122 ADRA2A gene polymorphisms are modifiers of CF severity.

Cystic fibrosis (CF) has clinical variability associated with CFTR genetic mutations, environmental factors and modifier genes. Genes associated with the inflammatory process are important for understanding CF variability as well as identifying new therapies and prognostic factors. Because of the importance of COX-2 in inflammation, COX-2 polymorphisms were studied in a CF population and compared with 27 clinical variables with consideration of the CFTR mutations. There were 106CF patients included in the study, and the rs20417 and rs5275 COX-2 gene polymorphisms were analyzed using the RFLP technique. The polymorphism -8473C>T was associated with nasal polyposis in the CC+CT genotype (OR=5.552, IC=1.318-38.37) without taking the CFTR mutations into account. The haplotype analysis showed an association with nasal polyposis (NP) and diabetes mellitus (DM). NP was associated with the GG/TT haplotype (OR=0.1056, IC=0.004-0.642) in patients without taking the CFTR mutations into account. DM was associated with the GC/TC haplotype, (OR=6.164, IC=1.719-23.83) in patients with two identified CFTR mutations. The association of COX-2 polymorphisms with CF was not clear. In the literature, only one study considering these polymorphisms and CF was found, and that study did not include CF comorbidities in the clinical variables. Therefore, our study provides the first evidence showing an association between the COX-2 gene and the CF comorbidities of NP and DM. In recent years, the prognosis and life expectancy of CF patients has improved, and the comorbidities have increased as a result. A better understanding of the complex aspects involved in CF comorbidities could provide a better treatment, primarily in older CF patients.