The following is a summary of “Novel Variants and Phenotypes in NEUROG3-Associated Syndrome,” published in the January 2023 issue of Endocrinology & Metabolism by Wejaphikul, et al.
Malabsorptive diarrhea, insulin-dependent diabetes mellitus (IDDM), and sporadic hypogonadotropic hypogonadism are all brought on by biallelic pathogenic mutations in the NEUROG3 gene. The clinical and mutational spectra of the illness were far from comprehensive, with only 17 recorded instances. For a study, researchers sought to investigate the pathogenicity of the newly discovered pathogenic mutations using luciferase reporter assays and western blot in 3 unrelated Thai patients who presented with early-onset malabsorptive diarrhea, endocrine abnormalities, and kidney impairments.
Congenital diarrhea cases were sought from three unrelated individuals. Comprehensive clinical and endocrinological characteristics were gathered. To find mutations, exome sequencing was used, and in vitro, functional tests, such as the luciferase reporter assay, were investigated to confirm their pathogenicity.
The patients also showed previously unreported proximal renal tubulopathy (Patient 2,3) and pituitary gland hypoplasia with multiple pituitary hormone deficiencies (Patient 1, 2, and 3), in addition to malabsorptive diarrhea brought on by enteric anendocrinosis, IDDM, short stature, and delayed puberty. Patient 1 was homozygous for c.371C > G (p.Thr124Arg) in NEUROG3, whereas the other two patients were homozygous for c.284G > C (p.Arg95Pro) in NEUROG3, according to exome sequencing. Both variations had never before been documented. The transcriptional activity of NEUROG3 was hampered by these 2 variations, as shown by a luciferase reporter test.
In the study, individuals with NEUROG3-associated disease were shown to have pituitary gland hypoplasia, numerous pituitary hormone deficits, proximal renal tubulopathy, and 2 newly discovered NEUROG3 loss-of-function variations.
Reference: academic.oup.com/jcem/article-abstract/108/1/52/6712598?redirectedFrom=fulltext