RESUMO
SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system. Despite its important developmental roles, SOX5 disruption has yet to be associated with human disease. We report one individual with a reciprocal translocation breakpoint within SOX5, eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent), and seven individuals with larger 12p12 deletions encompassing SOX5. Common features in these subjects include prominent speech delay, intellectual disability, behavior abnormalities, and dysmorphic features. The phenotypic impact of the deletions may depend on the location of the deletion and, consequently, which of the three major SOX5 protein isoforms are affected. One intragenic deletion, involving only untranslated exons, was present in a more mildly affected subject, was inherited from a healthy parent and grandparent, and is similar to a deletion found in a control cohort. Therefore, some intragenic SOX5 deletions may have minimal phenotypic effect. Based on the location of the deletions in the subjects compared to the controls, the de novo nature of most of these deletions, and the phenotypic similarities among cases, SOX5 appears to be a dosage-sensitive, developmentally important gene.
Assuntos
Transtornos Dismórficos Corporais/genética , Deficiências do Desenvolvimento/genética , Haploinsuficiência , Transtornos do Desenvolvimento da Linguagem/genética , Transtornos Mentais/genética , Fatores de Transcrição SOXD/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Cromossomos Humanos Par 12 , Feminino , Humanos , MasculinoRESUMO
Information in the medical literature regarding adults with genetic syndromes is limited, making the care of these patients challenging. We conducted a questionnaire study of adults with Rubinstein-Taybi syndrome that addressed medical problems, education, independence, and behavior. The most common medical problems included short stature, obesity, visual difficulties, keloids, eating problems, spine curvature, and joint problems. The adults had typically moderate mental retardation, but most achieved some independence in self-care and communication; many participated in supported work situations. However, approximately one-third were said to have some decreased abilities over time. Behavior problems were common and often worsened with age. Very few of the study participants were seeing a geneticist as an adult. Long-term involvement of geneticists and education of adult primary care providers may help with many of the challenges facing adults with RTS and their families.
