RESUMEN
The most common etiology of non-syndromic monogenic obesity are mutations in gene for the Melanocortin-4 receptor (MC485) with variable prevalence in different countries (1.2-6.3 % of obese children). The aim of our study was 1) to search for MC4R mutations in obese children in Slovakia and compare their prevalence with other European countries, and 2) to describe the phenotype of the mutation carriers. DNA analysis by direct Sanger sequencing of the coding exons and intron/exon boundaries of the MC4R gene was performed in 268 unrelated Slovak children and adolescents with body mass index above the 97(th) percentile for age and sex and obesity onset up to 11 years (mean 4.3+/-2.8 years). Two different previously described heterozygous loss of function MC4R variants (i.e. p.Ser19Alafs*34, p.Ser127Leu) were identified in two obese probands, and one obese (p.Ser19Alafs*34), and one lean (p.Ser127Leu) adult family relatives. No loss of function variants were found in lean controls. The prevalence of loss-of-function MC4R variants in obese Slovak children was 0.7 %, what is one of the lowest frequencies in Europe.
Asunto(s)
Obesidad Infantil/genética , Receptor de Melanocortina Tipo 4/genética , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Genotipo , Heterocigoto , Humanos , Masculino , Fenotipo , EslovaquiaRESUMEN
OBJECTIVE: Autosomal dominant familial diabetes insipidus (FNDI) is a rare disease characterized by polydipsia and polyuria due to deficiency of the antidiuretic hormone, arginine vasopressin (AVP). We report the first Slovak family with the disease. Noteworthy is the concordantly belated debut of the disease symptoms in two monozygotic twin proband girls in the age of 17 years. Because of inconclusive results of water deprivation test consistent with partial diabetes insipidus (DI), missing "bright spot" of posterior pituitary gland in T1-weighted magnetic resonance imaging and family occurrence of polyuria and polydipsia on anamnestic evaluation. METHODS: Molecular genetic testing of the AVP gene was proceeded, because of the inconclusive results of water deprivation test consistent with partial diabetes insipidus, missing "bright spot" of posterior pituitary gland in T1-weighted magnetic resonance imaging and family occurrence of polyuria and polydipsia on anamnestic evaluation. RESULTS: Genetic analysis revealed a heterozygous g.279G>A substitution that predicts a p.Ala19Thr substitution in the signal peptide of the AVP prohormone. The wide intrafamiliar variations (3 to 17 years) in disease onset together with the concordantly delayed debut of polyuria in two monozygotic twin girls suggest that individual differences in genetic influences family environmental factors may modify the penetrance of the mutation of the AVP gene. CONCLUSIONS: The present paper supports the notion that molecular genetic evaluation should be performed in all patients with familial occurrence of DI regardless of the clinical results.