Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. GCK -MODY and HNF1A -MODY are the prevalent subtypes. Currently, there is growing concern regarding the correct interpretation of molecular genetic findings. The American College of Medical Genetics and Genomics (ACMG) updated guidelines to interpret and classify molecular variants. This study aimed to determine the prevalence of MODY ( GCK / HNF1A ) in a large cohort of Brazilian families, to report variants related to phenotype, and to classify them according to ACMG guidelines. One hundred and nine probands were investigated, 45% with clinical suspicion of GCK -MODY and 55% with suspicion of HNF1A -MODY. Twenty-five different variants were identified in GCK gene (30 probands-61% of positivity), and 7 variants in HNF1A (10 probands-17% of positivity). Fourteen of them were novel (12- GCK /2- HNF1A ). ACMG guidelines were able to classify a large portion of variants as pathogenic (36%- GCK /86%- HNF1A ) and likely pathogenic (44%- GCK /14%- HNF1A ), with 16% (5/32) as uncertain significance. This allows us to determine the pathogenicity classification more efficiently, and also reinforces the suspected associations with the phenotype among novel variants.
The height response to the use of growth hormone in short height cases has already been confirmed in the literature. The influence of the insulin-like growth factor 1 (GH-IGF1) axis components on development, function, regeneration, neuroprotection, cognition, and motor functions has been evaluated in experimental studies and in adults with central nervous system lesions. However, there is still little research on the clinical impact of hormone replacement on neurological and psychomotor development. This report presents the case of a patient with excellent weight-height recovery and, even more surprisingly, neurological and psychomotor development in response to use of growth hormone. The result strengthens the correlation between experimental and clinical findings related to cerebral plasticity response to growth hormone in children. A preterm male patient with multiple health problems during the neonatal and young infancy period, who for six years presented with a relevant deficit in growth, bone maturation, and neurological and psychomotor development. At six years of age, he had low stature (z-score −6.89), low growth rate, and low weight (z-score −7.91). He was incapable of sustaining his axial weight, had not developed fine motor skills or sphincter control, and presented with dysfunctional swallowing and language. Supplementary tests showed low IGF-11 levels, with no changes on the image of the hypothalamus-pituitary region, and bone age consistent with three-year-old children — for a chronological age of six years and one month. Growth hormone replacement therapy had a strong impact on the weight-height recovery as well as on the neurological and psychomotor development of this child.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.