RESUMO
Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.
Assuntos
População Negra/genética , Fissura Palatina/genética , Genética Populacional , Genoma Humano , Genômica , Locos de Características Quantitativas , Alelos , Animais , Mapeamento Cromossômico , Modelos Animais de Doenças , Elementos Facilitadores Genéticos , Feminino , Expressão Gênica , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genômica/métodos , Genótipo , Humanos , Masculino , Camundongos , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Orofacial clefts are the most common malformations of the head and neck region. Genetic and environmental factors have been implicated in the etiology of these traits. METHODS: We recently conducted genotyping of individuals from the African population using the multiethnic genotyping array (MEGA) to identify common genetic variation associated with nonsyndromic orofacial clefts. The data cleaning of this dataset allowed for screening of annotated sex versus genetic sex, confirmation of identify by descent and identification of large chromosomal anomalies. RESULTS: We identified the first reported orofacial cleft case associated with paternal uniparental disomy (patUPD) on chromosome 22. We also identified a de novo deletion on chromosome 18. In addition to chromosomal anomalies, we identified cases with molecular karyotypes suggesting Klinefelter syndrome, Turner syndrome and Triple X syndrome. CONCLUSION: Observations from our study support the need for genetic testing when clinically indicated in order to exclude chromosomal anomalies associated with clefting. The identification of these chromosomal anomalies and sex aneuploidies is important in genetic counseling for families that are at risk. Clinicians should share any identified genetic findings and place them in context for the families during routine clinical visits and evaluations.
Assuntos
Transtornos Cromossômicos/genética , Fenda Labial/genética , Fissura Palatina/genética , Trissomia/genética , Dissomia Uniparental/genética , Adulto , Criança , Deleção Cromossômica , Transtornos Cromossômicos/patologia , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 22/genética , Fenda Labial/patologia , Fissura Palatina/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mosaicismo , Trissomia/patologia , Dissomia Uniparental/patologiaRESUMO
OBJECTIVES: To determine the pattern of presentation, prevalent age, hospital incidence, and outcome of management of prostate cancer in our environment. METHOD: Patients with histopathology evidence of prostate cancer managed between January 1991 and December 2007 were studied. Information entered into a pro-forma sheet and analyzed included the age of patients, clinical features, investigations, histopathology diagnosis, outcome of management, and duration of follow-up. RESULTS: During the period, 189 patients aged 46-99 years (mean, 68.0; 9.8 SD) confirmed and managed for prostate cancer were studied. The average hospital incidence (2002-2004) was 182.5 per 10(5) male admissions with 15.1-month mean duration of symptoms. Most 178 (94.2%) patients presented with advanced diseases, with 1 or multiple complications in 172 (91.0%), obstructive lower urinary tract symptoms 156 (82.5%), distant metastasis 97 (51.3%), lower back pain 95 (50.3%), weight loss 95 (50.3%), hematuria 86 (45.5%), anemia 77 (40.7%), renal failure 74 (39.2%), and inability to walk 42 (22.2%). Eighty-nine (47.0%) patients were farmers, 111 (58.7%) indulged in alcohol, and 46 (24.3%) smoked cigarettes. Mean prostate-specific antigen results available in 53 patients was 106.0 ng/mL (187.2SD) and digital rectal examination was valuable in diagnosis. Adenocarcinoma (186 [98.4%]) was the main histopathology type and most patients 136 (71.9%) had bilateral orchidectomy with or without antiandrogens. Mean duration of follow-up was 83.7 weeks. CONCLUSIONS: The burden of prostate cancer in our developing community is worrisome. It is prevalent between 46 and 99 years in our community. Presentation is late, often with urinary retention and other complications. In our setting, treatment is still essentially palliative with orchidectomy, which we found to be beneficial, acceptable, and the most affordable to our patients.