MODY probability calculator for GCK and HNF1A screening in a multiethnic background population

• Published in: Archives of Endocrinology and Metabolism 2020-02, Vol.64 (1), p.17-23
• Main Authors: Tarantino, Roberta Magalhães, Abreu, Gabriella de Medeiros, Fonseca, Ana Carolina Proença de, Kupfer, Rosane, Pereira, Maria de Fátima Carvalho, Campos, Mario, Zajdenverg, Lenita, Rodacki, Melanie
• Format: Article
• Language: English
• Subjects: GCK; HNF1A; MODY; monogenic diabetes; Original
• ISSN: 2359-3997; 2359-4292; 2359-4292
• DOI: 10.20945/2359-3997000000173

ABSTRACT Objective We aimed to identify the frequency of monogenic diabetes, which is poorly studied in multiethnic populations, due to GCK or HNF1A mutations in patients with suggestive clinical characteristics from the Brazilian population, as well as investigate if the MODY probability calculator (MPC) could help patients with their selection. Subjects and methods Inclusion criteria were patients with DM diagnosed before 35 years; body mass index < 30 kg/m2; negative autoantibodies; and family history of DM in two or more generations. We sequenced HNF1A in 27 patients and GCK in seven subjects with asymptomatic mild fasting hyperglycemia. In addition, we calculated MODY probability with MPC. Results We identified 11 mutations in 34 patients (32.3%). We found three novel mutations. In the GCK group, six cases had mutations (85.7%), and their MODY probability on MPC was higher than 50%. In the HNF1A group, five of 27 individuals had mutations (18.5%). The MPC was higher than 75% in 11 subjects (including all five cases with HNF1A mutations). Conclusion Approximately one third of the studied patients have GCK or HNF1A mutations. Inclusion criteria included efficiency in detecting patients with GCK mutations but not for HNF1A mutations (< 20%). MPC was helpful in narrowing the number of candidates for HNF1A screening.