Comprehensive genetic screening reveals wide spectrum of genetic variants in monogenic forms of diabetes among Pakistani population  

作　　者：Ibrar Rafique Asif Mir Shajee Siddiqui Muhammad Arif Nadeem Saqib Asher Fawwad Luc Marchand Muhammad Adnan Muhammad Naeem Abdul Basit Constantin Polychronakos 

机构地区：[1]Department of Biological Sciences,International Islamic University,Islamabad 44000,Pakistan [2]Departments of Pediatrics and Human Genetics,McGill University Health Centre Research Institute,Montreal H4A 3J1,Canada [3]Research Development and Coordination,Pakistan Health Research Council,Islamabad 44000,Pakistan [4]Department of Medicine,Pakistan Institute of Medical Sciences,Islamabad 44000,Pakistan,Pakistan [5]Department of Medical Laboratory Technology,National Skills University,Islamabad,44000,Pakistan [6]Department of Biochemistry,Baqai Institute of Diabetology and Endocrinology,Baqai Medical University,Karachi 74600,Sindh,Pakistan [7]PHRC Research Centre,FJMU,Pakistan Health Research Council,Lahore 54000,Pakistan [8]Department of Biotechnology,Quaid-I-Azam University,Islamabad 44000,Pakistan [9]Department of Medicine,Baqai Institute of Diabetology and Endocrinology,Baqai Medical University,Karachi 74600,Sindh,Pakistan

出　　处：《World Journal of Diabetes》2021年第11期1957-1966,共10页世界糖尿病杂志（英文版）（电子版）

基　　金：Canadian Institutes of Health Research,No.PJT-159715.

摘　　要：BACKGROUND Monogenic forms of diabetes(MFD)are single gene disorders.Their diagnosis is challenging,and symptoms overlap with type 1 and type 2 diabetes.AIM To identify the genetic variants responsible for MFD in the Pakistani population and their frequencies.METHODS A total of 184 patients suspected of having MFD were enrolled.The inclusion criterion was diabetes with onset below 25 years of age.Brief demographic and clinical information were taken from the participants.The maturity-onset diabetes of the young(MODY)probability score was calculated,and glutamate decarboxylase ELISA was performed.Antibody negative patients and features resembling MODY were selected(n=28)for exome sequencing to identify the pathogenic variants.RESULTS A total of eight missense novel or very low-frequency variants were identified in 7 patients.Three variants were found in genes for MODY,i.e.HNF1A(c.169C>A,p.Leu57Met),KLF11(c.401G>C,p.Gly134Ala),and HNF1B(c.1058C>T,p.Ser353Leu).Five variants were found in genes other than the 14 known MODY genes,i.e.RFX6(c.919G>A,p.Glu307Lys),WFS1(c.478G>A,p.Glu160Lys)and WFS1(c.517G>A,p.Glu173Lys),RFX6(c.1212T>A,p.His404Gln)and ZBTB20(c.1049G>A,p.Arg350His).CONCLUSION The study showed wide spectrum of genetic variants potentially causing MFD in the Pakistani population.The MODY genes prevalent in European population(GCK,HNF1A,and HNF4a)were not found to be common in our population.Identification of novel variants will further help to understand the role of different genes causing the pathogenicity in MODY patient and their proper management and diagnosis.

关 键 词：MODY DIABETES GENETICS Monogenic diabetes Monogenic forms of diabetes 

分 类 号：R587.1[医药卫生—内分泌]