Clinical and Genetic Heterogeneity of Familial Early-Onset Diabetes: Case of Six Tunisian Patients Suspected of Maturity-Onset Diabetes of the Young 12

Background and objective: Maturity-onset diabetes of the young 12 (MODY12) is a form of early-onset type 2 diabetes, which is transmitted in an autosomal dominant mode. It has clinical features similar to MODY1 and MODY3. The aim of this study is to screen for mutations in ABCC8 gene in six Tunisian patients suspected of MODY12 using Sanger sequencing. Methods: Six probands, with diabetes in 2-3 generations and found previously negative for mutations in HNF1A, HNF4A, INS, IPF1 and NEUROD1, were screened for known mutations in ABCC8 gene using Sanger sequencing. A comparison of the clinical features of our patients with MODY12 cohorts of other studies was also performed using ANOVA test. Results: The six patients were diagnosed with overt diabetes (fasting glycemia: 12.85 ± 3.5 mmol/l, HbA1c: 12.51 ± 2.58%) at mean age of 25.16 ± 5.11 years. They had a BMI mean equal to 26.7 ± 5.9 kg/m2. The majority of the patients were initially treated with OHA or on diet. Some of them converted to insulin therapy. Although, the comparison of our cohort with other MODY12 cohorts showed no significant difference in age at diagnostic and HbA1c, molecular analysis showed only two synonymous non-pathological polymorphisms rs1799857 and rs1805036. Conclusion: Our study highlighted the clinical and genetic heterogeneity of familial earlyonset diabetes in the Tunisian population, which is concordant with previous studies Thus, the need for using nextgeneration sequencing technologies to determine the aetiology of these forms of diabetes.

Research of the origin of a particular Tunisian group using a physical marker and Alu insertion polymorphisms

The aim of this study was to show how, in some particular circumstances, a physical marker can be used along with molecular markers in the research of an ancient people movement. A set of five Alu insertions was analysed in 42 subjects from a particular Tunisian group (El Hamma) that has, unlike most of the Tunisian population, a very dark skin, similar to that of sub-Saharans, and in 114 Tunisian subjects (Gabes sample) from the same governorate, but outside the group. Our results showed that the El Hamma group is genetically midway between sub-Saharan populations and North Africans, whereas the Gabes sample is clustered among North Africans. In addition, The A25 Alu insertion, considered characteristic to sub-Saharan Africans, was present in the El Hamma group at a relatively high frequency. This frequency was similar to that found in sub-Saharans from Nigeria, but significantly different from those found in the Gabes sample and in other North African populations. Our molecular results, consistent with the skin color status, suggest a sub-Saharan origin of this particular Tunisian group.

Does minor histocompatibility antigen HA-1 disparity affect the occurrence of graft-versus-host disease in tunisian recipients of hematopoietic stem cells?

INTRODUCTION: Minor histocompatibility antigen HA-1 (MiHAg-HA-1) disparity between a patient and his or her human leukocyte antigen (HLA) genoidentical donor has been widely associated with an increased risk of graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. OBJECTIVE: To examine the effect of HA-1 disparity on the incidence of both acute and chronic graft-versus-host disease in Tunisian recipients of hematopoietic stem cells. METHODS: A total of 60 patients and their 60 respective sibling hematopoietic stem cell donors were enrolled in this study. All patients prophylactically received cyclosporine A and/or methotrexate for graft-versus-host disease. An HA-1 genotyping assay was performed with the SSP-PCR method, and HLA-A*0201- and/or HLA-A*0206-positive samples were identified using the Luminex HLA typing method. RESULTS: The Luminex HLA typing assay showed that 54 patients were positive for either the HLA-A*0201 or HLA-A*0206 alleles. Among these cases, six pairs were mismatched for MiHAg-HA-1. Both acute and chronic graft-versus-host disease occurred in four mismatched patients (Fisher's p-values were 0.044 and 0.170, respectively). A univariate logistic regression model analysis showed that only acute graft-versus-host disease may be affected by recipient MiHAg-HA-1 disparity (p: 0.041, OR: 6.727), while chronic graft-versus-host disease correlates with both age and recipient/donor sex mismatch (p: 0.014, OR: 8.556 and p: 0.033, OR: 8.664, respectively). CONCLUSION: Our findings support previously reported data suggesting a significant association between HA-1 disparity and the risk of acute graft-versus-host disease following hematopoietic stem cell transplantation.