Persistent pulmonary hypertension of the new-borns (PPHN) is one of the main etiologies of morbidity as well as mortality in neonates. Previous studies found that genetic polymorphisms in urea cycle e Show more
Persistent pulmonary hypertension of the new-borns (PPHN) is one of the main etiologies of morbidity as well as mortality in neonates. Previous studies found that genetic polymorphisms in urea cycle enzymes are associated with PPHN. Few of the genetic polymorphisms in neonates have been recognized with PPHN. We aimed to find out the prevalence of the CPS-I gene polymorphism and to correlate the genotype with the serum nitric oxide (NO) levels in Egyptian neonates with idiopathic PPHN. We included neonates diagnosed with PPH (n = 150) while the control group included healthy neonates with matched age and sex (n = 100). The CPS-I gene polymorphism: A/C, trans-version substitution, rs4399666 genotype was identified using TaqMan-based quantitative PCR. The results revealed that the CPS-I A/C rs4399666 gene polymorphism and lower serum NO levels were significantly associated with idiopathic PPHN in neonates. In addition, serum NO level was significantly associated with an rs4366999 A/C variant gene in idiopathic PPHN (p = 0.001). Univariable regression analysis demonstrated that there was a significant association between CPS-I A/C rs4399666 CC and increased risk of PPHN (odd ratio, 95% CI of 1.8 (0.78 to 1.75), p-value = 0.04).Conclusion: We concluded that mutant CPS-I A/C rs4399666 minor variant especially the homozygous CC genotype is frequently distributed among the PPHN group. This demonstrates that the presence of mutant CPS-I rs4399666 does not necessarily predispose to the development of PPHN in neonates, but nonetheless, if the C allele is inherited in the homozygous CC genotype, it is associated with a higher risk of PPHN. What is Known: • Prior studies found that polymorphisms in urea cycle enzyme genes are associated with PPHN. • Association between CPS-1 gene polymorphisms is significantly associated with PPHN. What is New: • The prevalence of CPS-1, A/C trans-version substitution, rs4399666 gene polymorphism in Egyptian neonates presented with idiopathic PPHN. • Mutant CPS-I A/C rs4399666 especially the homozygous CC genotype is more frequently distributed among PPHN, and it is significantly associated with low serum nitric oxide level. Show less
The objective of the study was to evaluate the epidemiology of patients with congenital myasthenic syndrome (CMS) in Israel. Targeted mutation analysis was performed based on the clinical symptoms and Show more
The objective of the study was to evaluate the epidemiology of patients with congenital myasthenic syndrome (CMS) in Israel. Targeted mutation analysis was performed based on the clinical symptoms and electrophysiological findings for known CMS. Additional specific tests were performed in patients of Iranian and/or Iraqi Jewish origin. All medical records were reviewed and clinical data, genetic mutations and outcomes were recorded. Forty-five patients with genetic mutations in known CMS genes from 35 families were identified. Mutations in RAPSN were identified in 13 kinships in Israel. The most common mutation was c.-38A>G detected in 8 patients of Iranian and/or Iraqi Jewish origin. Four different recessive mutations in COLQ were identified in 11 kinships, 10 of which were of Muslim-Arab descent. Mutations in CHRNE were identified in 7 kinships. Less commonly detected mutations were in CHRND, CHAT, GFPT1 and DOK7. In conclusion, mutations in RAPSN and COLQ are the most common causes of CMS in our cohort. Specific mutations in COLQ, RAPSN, and CHRNE occur in specific ethnic populations and should be taken into account when the diagnosis of a CMS is suspected. Show less