RESUMO
BACKGROUND: The Pierre Robin sequence (PRS), consisting of cleft palate, micrognathia and glossoptosis, can be seen as part of the phenotype in other Mendelian syndromes--for instance, campomelic dysplasia (CD) which is caused by SOX9 mutations--but the aetiology of non-syndromic PRS has not yet been unravelled. OBJECTIVE: To gain more insight into the aetiology of PRS by studying patients with PRS using genetic and cytogenetic methods. METHODS: 10 unrelated patients with PRS were investigated by chromosome analyses and bacterial artificial chromosome arrays. A balanced translocation was found in one patient, and the breakpoints were mapped with fluorescence in situ hybridisation and Southern blot analysis. All patients were screened for SOX9 and KCNJ2 mutations, and in five of the patients expression analysis of SOX9 and KCNJ2 was carried out by quantitative real-time PCR. RESULTS: An abnormal balanced karyotype 46,XX, t(2;17)(q23.3;q24.3) was identified in one patient with PRS and the 17q breakpoint was mapped to 1.13 Mb upstream of the transcription factor SOX9 and 800 kb downstream of the gene KCNJ2. Furthermore, a significantly reduced SOX9 and KCNJ2 mRNA expression was observed in patients with PRS. CONCLUSION: Our findings suggest that non-syndromic PRS may be caused by both SOX9 and KCNJ2 dysregulation.
Assuntos
Regulação da Expressão Gênica , Proteínas de Grupo de Alta Mobilidade/genética , Síndrome de Pierre Robin/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Fatores de Transcrição/genética , Adolescente , Pareamento de Bases/genética , Criança , Pré-Escolar , Quebra Cromossômica , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 2/genética , Feminino , Proteínas de Grupo de Alta Mobilidade/metabolismo , Humanos , Hibridização in Situ Fluorescente , Linfócitos/metabolismo , Masculino , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição SOX9 , Fatores de Transcrição/metabolismo , Translocação GenéticaRESUMO
STUDY DESIGN: A total of 215 consecutive patients treated either by bracing or operation received a questionnaire after 9.7 years. OBJECTIVE: The aim of the present study was to elucidate the long-term outcome in a group of brace (BT) or surgical treated (ST) patients suffering AIS. SUMMARY OF BACKGROUND DATA: In adolescent idiopathic scoliosis (AIS), the options are BT or ST and, together with the disease itself, they may both be physically and psychologically demanding. METHODS: The main topics of a questionnaire were demographics, back pain, activities of daily living, and SF-36. RESULTS: A total of 181 replied. The mean age at follow-up was 26.0 years. The level of back or leg pain was relatively low, and the BT patients had more pain than their ST peers. We saw a generally high level of ADL and found no significant difference between BT and ST patients in the present study for any of the SF-36 variables. Compared with age-matched controls, the SF-36 scores were lower in the AIS patients. Brace related questions revealed a significant impact of the disease and the treatment on the patients' lives. CONCLUSIONS: The patients had moderately reduced perceived health status and activities of daily living, and increased pain with the ST patients generally at a better level than the BT.