NA = not applicable; PNDM = permanent neonatal diabetes mellitus

Genes are listed in alphabetic order.

See Table A. Genes and Databases for chromosome locus and protein.

Flanagan et al [2014] and data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

See Molecular Genetics for information on variants detected in these genes.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.

Large deletions/duplication have been reported in individuals with additional phenotypes (see Phenotype Correlations by Gene and Genetically Related Disorders). To date, large deletions/duplications have not been reported in individuals with isolated PNDM [Stenson et al 2020].

Biallelic EIF2KA3 pathogenic variants are associated with Wolcott-Rallison syndrome. However, PNDM may be the first clinical manifestation, and therefore EIF2KA3 should be considered in those presenting with apparently isolated PNDM.

Activating pathogenic variants in KCNJ11 cause PNDM; deletion/duplication analysis is not expected to identify PNDM-related pathogenic variants in KCNJ11.

Analysis of PTF1A should include sequencing of the downstream enhancer, which accounts for >60% of PNDM-related pathogenic variants in this gene [Demirbilek et al 2020].

The 26-bp insertion and complex rearrangement in SLC2A2 each reported in an individual with Fanconi-Bickel syndrome should be detectable by sequence analysis.

Relative hypomethylation within the 6q24 differentially methylated region (DMR) has been reported in one individual to date with PNDM [Cao et al 2017]. Findings reported in the individual included severe intrauterine growth restriction, hyperglycemia beginning in the neonatal period, and absence of ketoacidosis. 6q24 DMR relative hypomethylation is typically associated with transient neonatal diabetes mellitus (see Diabetes Mellitus, 6q24-Related Transient Neonatal).

De Franco et al [2015]