[Etiological dissection in common anti-islet autoantibody-negative patients with type 1 diabetes].
OBJECTIVE
To explore the immunological and genetic factors of common anti-islet autoantibody-negative patients with type 1 diabetes.


METHODS
Specimens of peripheral blood were collected from 33 common autoantibody (GAD-Ab, IA2-Ab, IAA, TGA and TPO-Ab) negative diabetic patients with new-onset of unprovoked ketosis (or ketoacidosis), and genome DNA was extracted. The antibodies to carboxypeptide-H (CPH) and SOX13 (ICA12) were detected by radioligand assay. The gene mutations of MODY3 (HNF-1alpha) and MODY6 (NeuroD1/Beta2) were detected by PCR-SSCP sequencing. Mitochondrial gene mutations were analyzed with PCR-RFLP.


RESULTS
Two (6%) of the patients were SOX13-Ab positive, while none of them was positive for CPH-Ab. Gene mutation detection found one case of a new mutation, R321H (CGC-->CAC) in the exon 5 of HNF-1alpha gene and one case with ND1 mt3316 G-->A mutation in mitochondrial DNA. In addition to the diabetes-associated mutations described above, seven polymorphisms of HNF-1alpha gene, including L17L, I27L, L459L, S487N, IVS5 + 9 C > G, IVS6-42 G > T, and IVS7 + 7 G > A, and one NeuroD1/Beta2 gene polymorphic variant Ala45Thr, were found.


CONCLUSIONS
Autoimmunity and gene mutations (such as MODY3 and mitochondrial genes mutations) may be etiological in a few cases initially diagnosed as autoantibody-negative type 1 diabetes. Autoimmunity and MODY and mitochondrial diabetes should be excluded if idiopathic type 1 (type 1B) diabetes is diagnosed.
Zhang
Dong-mei
DM
Institute of Metabolism & Endocrinology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Zhou
Zhi-guang
ZG
Weng
Jian-ping
JP
Li
Li-rong
LR
Deng
Hao
H
Zhang
Chi
C
Jin
Ping
P
Huang
Gan
G
Peng
Jian
J
Xiu
Ling-ling
LL
Wang
Jian-ping
JP
Yang
Lin
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D043423:Carboxypeptidase H / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D006609:High Mobility Group Proteins / Q000276:immunology*; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000276:immunology; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D055755:SOXD Transcription Factors; D014157:Transcription Factors / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; C491720:SOX13 protein, human; D055755:SOXD Transcription Factors; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D043423:Carboxypeptidase H