Characterization of monogenic diabetes among Sudanese children: a multi-center experience from a population with high consanguinity.
PMID 41275391 | PMCID PMC12780942 | DOI 10.1515/jpem-2025-0316 · Journal of pediatric endocrinology & metabolism : JPEM · 2026
OBJECTIVES: Monogenic diabetes (MD) is a group of diabetes subtypes caused by defects in single genes. We report phenotypes and genotypes of MD among Sudanese children. METHODS: Referred patients (from birth to 18 years of age) with diabetes and a clinical diagnosis of MD to Gaafar Ibnauf Pediatric Tertiary Hospital or the Sudan Childhood Diabetes Center between January 2006 and April 2023 were included. Patients were divided into two groups based on onset of diabetes before six months of age (Group 1, or neonatal diabetes mellitus) or after (Group 2, or non-neonatal diabetes mellitus). Genetic testing was performed for 87 patients at the Exeter Genomics laboratory and for one patient at the University of Cambridge, Metabolic Research Laboratories, UK. RESULTS: Out of 88 patients, 50 were from Group 1 and 38 from Group 2. We reported consanguinity in 63.6 % of the cohort and identified disease-causing variants for 18 genes in 43.2 % (Group 1) and 37.5 % (Group 2) of patients from the total cohort. The commonest causes in Group 1 and Group 2 were pathogenic variants in the EIF2AK3 and WFS1 genes, respectively. Pathogenic variants in recently reported novel genes ZNF808, NARS2, and FICD were detected in 8.5 %, 4.2%, and 1.4 % of patients, respectively. Patients with a disrupted WFS1 gene were found to have deafness (92.8 %) and optic atrophy (64 %). While skeletal deformities and liver disease were both seen in 28.6 % of patients with pathogenic variants in the ElF2AK3 gene. Hepatomegaly and hypophosphatemic rickets were uniformly seen in patients with pathogenic variants in the SLC2A2 gene. Generalized subcutaneous tissue loss and acanthosis nigricans were main features in AGPAT2 and INSR variants, respectively. CONCLUSIONS: Characterization of MD in Sudan showed a predominance of syndromic forms. Genetic studies conducted on consanguineous populations may raise higher probabilities in identifying rare genes.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | EIF2AK3 | “The commonest causes in Group 1 and Group 2 were pathogenic variants in the EIF2AK3 and WFS1 genes, respectively.” | 0.98 | hgnc_dict_v1 |
| gene | WFS1 | “The commonest causes in Group 1 and Group 2 were pathogenic variants in the EIF2AK3 and WFS1 genes, respectively.” | 0.98 | hgnc_dict_v1 |
| gene | ZNF808 | “Pathogenic variants in recently reported novel genes ZNF808, NARS2, and FICD were detected in 8.5 %, 4.2%, and 1.4 % of patients, respectively.” | 0.98 | hgnc_dict_v1 |
| gene | NARS2 | “Pathogenic variants in recently reported novel genes ZNF808, NARS2, and FICD were detected in 8.5 %, 4.2%, and 1.4 % of patients, respectively.” | 0.98 | hgnc_dict_v1 |
| gene | FICD | “Pathogenic variants in recently reported novel genes ZNF808, NARS2, and FICD were detected in 8.5 %, 4.2%, and 1.4 % of patients, respectively.” | 0.98 | hgnc_dict_v1 |
| gene | SLC2A2 | “Hepatomegaly and hypophosphatemic rickets were uniformly seen in patients with pathogenic variants in the SLC2A2 gene.” | 0.98 | hgnc_dict_v1 |
| gene | AGPAT2 | “Generalized subcutaneous tissue loss and acanthosis nigricans were main features in AGPAT2 and INSR variants, respectively.” | 0.98 | hgnc_dict_v1 |
| gene | INSR | “Generalized subcutaneous tissue loss and acanthosis nigricans were main features in AGPAT2 and INSR variants, respectively.” | 0.98 | hgnc_dict_v1 |
| phenotype | diabetes mellitus | “Characterization of monogenic diabetes among Sudanese children: a multi-center experience from a population with high consanguinity.” | 0.93 | phenotype_alias_lexicon_v2 |
| phenotype | hearing loss | “Patients with a disrupted WFS1 gene were found to have deafness (92.8 %) and optic atrophy (64 %).” | 0.93 | phenotype_alias_lexicon_v2 |
| population | Population | “Characterization of monogenic diabetes among Sudanese children: a multi-center experience from a population with high consanguinity. Genetic testing was performed for 87 patients at the Exeter Genomics laboratory and for one patient at the University of Cambridge, Metabolic Research Laboratories, UK. We reported consanguinity in 63.6 % of the cohort and identified disease-causing variants for 18 genes in 43.2 % (Group 1) and 37.5 % (Group 2) of patients from the total cohort. Genetic studies conducted on consanguineous populations may raise higher probabilities in identifying rare genes.” | 0.80 | saudi_context_rules_v1 |