RESUMO
Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSP-related genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C>T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C>T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance.
Assuntos
Fatores de Troca do Nucleotídeo Guanina/genética , Proteínas de Choque Térmico/genética , Proteínas/genética , Paraplegia Espástica Hereditária/genética , Adolescente , Adulto , Criança , Feminino , Estudos de Associação Genética , Ligação Genética , Predisposição Genética para Doença , Heterozigoto , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Proteínas/metabolismo , Paraplegia Espástica Hereditária/diagnóstico por imagem , Paraplegia Espástica Hereditária/patologia , Adulto JovemRESUMO
OBJECTIVES: To describe the nature of geriatric medical admissions to teaching hospitals in three countries in Africa (Nigeria, Sudan, Tanzania) and compare them with data from the United Kingdom. DESIGN: Cross-sectional cohort study. SETTING: Federal Medical Centre, Idi-Aba, Abeokuta, Nigeria; Soba University Hospital, Khartoum, Sudan; Kilimanjaro Christian Medical Centre, Moshi, Tanzania; and North Tyneside General Hospital, North Shields, United Kingdom. PARTICIPANTS: All people aged 60 and older urgently medically admitted from March 1 to August 31, 2012. MEASUREMENTS: Data were collected regarding age, sex, date of admission, length of stay, diagnoses, medication, date of discharge or death, and discharge destination. RESULTS: In Africa, noncommunicable diseases (NCDs) accounted for 81.0% (n=708) of admissions (n=874), and tuberculosis, malaria, and the human immunodeficiency virus and acquired immunodeficiency syndrome accounted for 4.6% (n=40). Cerebrovascular accident (n=224, 25.6%) was the most common reason for admission, followed by cardiac or circulatory dysfunction (n=150, 17.2%). Rates of hypertension were remarkably similar in the United Kingdom (45.8%) and Africa (40.2%). CONCLUSIONS: In the elderly population, the predicted increased burden of NCDs on health services in Africa appears to have occurred. Greater awareness and some reallocation of resources toward NCDs may be required if the burden of such diseases is to be reduced.