Received: 13 January 2025 / Accepted: 15 May 2025 / Published Online: 24 May 2025
Abstract
Mutations in BCKDHA, BCKDHB, DLD and DBT are associated with Maple Syrup Urine Disease (MSUD) in different populations worldwide, therefore screening of these genes is crucial for genetic counseling, diagnosis and treatments of MSUD in patients suffering from MSUD. The present study was therefore carried out by screening MSUD patients from different regions including Baku, Sheki-Zagatala, Guba-Khachmaz, Lankaran-Astara zones to establish the genetic spectrum of MSUD patients of in Azerbaijan population. The cohort consisted of 800 patients clinically diagnosed with MSUD from the year 2015 to 2020. The gene panel sequencing (BCKDHA, BCKDHB, DLD and DBT) was performed by amplification of exonic sequences using the polymerase chain reaction (PCR) method followed by Sanger sequencing of the amplified product. For the confirmation of identified mutation a control panel of 140 healthy individuals was also collected from the population. The sequencing of the exonic sequence of the four genes resulted in identification of four missense variants. One patient carried compound heterozygous variants 1221(A>G) and 972 (C>T) in exon 9 and 10 respectively while another patient had homozygous 508(C>T) variant in BCKDHB, and homozygous 1199(A>G) was found in DBT in another patient. All the three patients carrying the identified mutations were from Guba-Khachmaz zone: one was Azerbaijani Turk, and two were Lezgi ethnic group. The in silico analysis predicted the variants to be pathogenic for protein function. In conclusion, the present study highlights the genetic role of BCKDHB and DBT in onset of MSUD in Azerbaijan especially Guba-Khachmaz zone where BCKDHB variants found to be more common in MSUD patient with followed by DBT. The identified variants were absent from the control group, thus suggesting their role in disease manifestation. Out of the 800 MSUD screened patients excluded cases might be having deep intronic mutation either in BCKDHB and DBT or other gene or might be having novel gene which could only be identified through exome/genome sequencing of the remaining patient.
