RESUMEN
Silver-Russell syndrome (SRS) is a rare genetic condition primarily characterized by growth restriction and facial dysmorphisms. While hypomethylation of H19/IGF2:IG-DMR (imprinting control region 1 [IC1]) located at 11p15.5 and maternal uniparental disomy of chromosome 7 (upd[7]mat) are the most common genetic mechanisms responsible for SRS, the expanding body of literature describing alternative causative variants suggests SRS is a highly heterogeneous condition, also involving variation in the HMGA2-PLAG1-IGF2 pathway. We report a familial PLAG1 deletion in association with a complex chromosomal rearrangement. We describe two siblings with differing unbalanced chromosomal rearrangements inherited from a mother with a 5-breakpoint balanced complex rearrangement involving chromosomes 2, 8, and 21. The overlapping but diverse phenotypes in the siblings were characterized by shared SRS-like features, underlined by a PLAG1 whole gene deletion. Genetic analysis and interpretation was further complicated by a meiotic recombination event occurring in one of the siblings. This family adds to the limited literature available on PLAG1-related SRS. We have reviewed all currently known cases aiming to define the associated phenotype and guide future genetic testing strategies. The heterogeneity of SRS is further expanded by the involvement of complex cytogenomic abnormalities, imposing requirements for a comprehensive approach to testing and genetic counseling.
Asunto(s)
Proteínas de Unión al ADN/genética , Pruebas Genéticas , Síndrome de Silver-Russell/genética , Niño , Preescolar , Metilación de ADN/genética , Femenino , Predisposición Genética a la Enfermedad , Impresión Genómica/genética , Proteína HMGA2/genética , Humanos , Factor II del Crecimiento Similar a la Insulina/genética , Masculino , Síndrome de Silver-Russell/diagnóstico , Síndrome de Silver-Russell/patologíaRESUMEN
Both vitamin D deficiency and polycystic ovary syndrome (PCOS) are associated with aspects of metabolic syndrome, but it is unclear whether vitamin D deficiency contributes to the metabolic disturbances commonly found in women with PCOS. This study sought to investigate (1) the prevalence of vitamin D deficiency in PCOS women in Scotland and (2) the relationship between vitamin D status and metabolic risk factors. This was an observational study on 52 women (25 in PCOS group and 27 in control group). Serum 25-hydroxyvitamin D concentrations less than 25 nmol/L were classified as severe vitamin D deficiency and were found in 44.0% and 11.2% of subjects in the PCOS and control groups, respectively (P = .047). Among the PCOS subjects, 25-hydroxyvitamin D concentrations were negatively correlated with body mass index (P = .033), C-reactive protein (P = .027), and free androgen index (P = .025) and positively correlated with quantitative insulin sensitivity check index (P = .035), high-density lipoprotein cholesterol (HDL-C) (P = .033), and sex hormone binding globulin (P = .038). Associations of vitamin D deficiency with quantitative insulin sensitivity check index and HDL-C were independent of body mass index and waist-to-hip ratio. Vitamin D deficiency is highly prevalent in PCOS women in Scotland, and a larger proportion of PCOS patients than control women were found to be vitamin D deficient. We also demonstrate correlations of vitamin D status with insulin sensitivity, HDL-C, and C-reactive protein in PCOS patients, which support the increasing evidence that vitamin D deficiency is associated with multiple metabolic risk factors in PCOS women.