Testing for monogenic diabetes is lower than required to reveal its true prevalence in an Australian population

Ali, Aleena Shujaat; Wong, Jay C.S.; Campbell, Ainsley; Ekinci, Elif I

doi:10.1016/j.deman.2022.100069

Cited by 2 publications

(1 citation statement)

References 18 publications

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“…Larger studies are required to examine the differential utility of the EMPC in white European versus non-white European populations. The previous smaller Australian studies have shown that non-white Europeans are overrepresented amongst participants with negative results on MODY genetic testing [ 7 , 12 ]. A UK study similarly found lower mutation detection in South Asians compared to white Europeans with suspected MODY (13% vs. 29%, p < 0.001) [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of monogenic diabetes in an Australian cohort using the Exeter maturity-onset diabetes of the young (MODY) probability calculator and next-generation sequencing gene panel testing

De Sousa,

Wu,

Colclough

et al. 2023

Acta Diabetol

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Aims This study aims to describe the prevalence of monogenic diabetes in an Australian referral cohort, in relation to Exeter maturity-onset diabetes of the young (MODY) probability calculator (EMPC) scores and next-generation sequencing with updated testing where relevant. Methods State-wide 5-year retrospective cohort study of individuals referred for monogenic diabetes genetic testing. Results After excluding individuals who had cascade testing for a familial variant (21) or declined research involvement (1), the final cohort comprised 40 probands. Incorporating updated testing, the final genetic result was positive (likely pathogenic/pathogenic variant) in 11/40 (27.5%), uncertain (variant of uncertain significance) in 8/40 (20%) and negative in 21/40 (52.5%) participants. Causative variants were found in GCK, HNF1A, MT-TL1 and HNF4A. Variants of uncertain significance included a novel multi-exonic GCK duplication. Amongst participants with EMPC scores ≥ 25%, a causative variant was identified in 37%. Cascade testing was positive in 9/10 tested relatives with diabetes and 0/6 tested relatives with no history of diabetes. Conclusions Contemporary genetic testing produces a high yield of positive results in individuals with clinically suspected monogenic diabetes and their relatives with diabetes, highlighting the value of genetic testing for this condition. An EMPC score cutoff of ≥ 25% correctly yielded a positive predictive value of ≥ 25% in this multiethnic demographic. This is the first Australian study to describe EMPC scores in the Australian clinic setting, albeit a biased referral cohort. Larger studies may help characterise EMPC performance between ethnic subsets, noting differences in the expected probability of monogenic diabetes relative to type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%