Abstract
Background: Alpha-1 antitrypsin (AAT) deficiency is a common genetic cause of childhood liver disorders. Its prevalence is highly variable around the world. Although this genetic deficiency is the main cause of neonatal jaundice, few studies have investigated AAT in Iran. Objectives: The current study aimed to investigate the association between specific alleles of AAT with idiopathic neonatal jaundice disease in patients with idiopathic jaundice. Methods: In this study, 30 neonates with a definitive diagnosis of neonatal cholestasis referred to Ghaem, and Dr. Sheikh hospitals in Mashhad (Iran) are included. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed on the extracted DNA from their blood samples. In the lack of commonly mutated alleles detected, the whole gene exons were DNA sequenced. Results: In the molecular test, we found no case of PiS or PiZ allele. The mutated alleles of PiS and PiZ were not appeared in patients with neonatal jaundice using the PCR-RFLP method. DNA sequencing was performed in 30 patients. Other rare missense variations were detected in the form of heterozygous (for Glu400Asp in 8 patients and Val237Ala in 2 patients), homozygous (for Glu400Asp in 1 patient), and compound heterozygous (for Glu400Asp/Val237Ala in 3 patients and Val237Ala/Asp280Val in 1 patient). Conclusions: The AAT deficiency caused by PiZ and PiS allelic variants was noted among infants with neonatal cholestasis in the Khorasan province of Iran. Other rare variants in the PiM might be caused by AAT deficiency and presenting the neonatal cholestasis. The possible functional study should be considered for the mutations identified.