Identification of insulin gene variants in neonatal diabetes.
OBJECTIVE
Permanent neonatal diabetes (PNDM) is caused by mutations in the genes responsible for the synthesis of different proteins that are important for the normal behavior of beta cells in the pancreas. Mutations in the insulin gene (INS) are considered as one of the causes of diabetes in neonates. This study aimed to investigate the genetic variations in the INS gene in a group of Egyptian infants diagnosed with PNDM.


METHODS
We screened exons 2 and 3 with intronic boundaries of the INS gene by direct gene sequencing in 30 PNDM patients and 20 healthy controls. A detailed clinical phenotyping of the patients was carried out to specify the diabetes features in those found to carry an INS variant.


RESULTS
We identified five variants (four SNPs and one synonymous variant), c(0).187 + 11T > C, c.-17-6T > A, c.*22A > C, c.*9C > T, and c.36G > A (p.A12A), with allelic frequencies of 96.7%, 80%, 75%, 5%, and 1.7%, respectively. All showed no statistically significance difference compared with the controls, with the exception of c.*22A > C.


CONCLUSIONS
Genetic screening for the INS gene did not reveal an evident role in the diagnosis of PNDM.
a Department of Clinical and Chemical Pathology , Kasr Al-Aini Hospital, Cairo University , Cairo , Egypt.
Nadida A
NA
Gohar
a Department of Clinical and Chemical Pathology , Kasr Al-Aini Hospital, Cairo University , Cairo , Egypt.
Walaa A
WA
Rabie
a Department of Clinical and Chemical Pathology , Kasr Al-Aini Hospital, Cairo University , Cairo , Egypt.
Sahar A
SA
Sharaf
a Department of Clinical and Chemical Pathology , Kasr Al-Aini Hospital, Cairo University , Cairo , Egypt.
Marwa M
MM
Elsharkawy
b Department of Pediatrics , Kasr Al-Aini Hospital, Cairo University , Cairo , Egypt , and.
Marwa F
MF
Mira
a Department of Clinical and Chemical Pathology , Kasr Al-Aini Hospital, Cairo University , Cairo , Egypt.
Aisha O
AO
Tolba
c Division of Newborn Services , The George Washington University and Children's National Medical Center , Washington , DC , USA.
Hany
H
Aly
D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D003920:Diabetes Mellitus / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics; D007328:Insulin / Q000235:genetics*; D008297:Male; D009154:Mutation
D007328:Insulin
DNA sequencing; insulin (INS) gene; mutations; permanent neonatal diabetes (PND)