RESUMO
In a survey of the chromosomal background associated with the sickle cell gene in Guadeloupe, a French Caribbean island, we identified 37 unrelated patients with sickle cell disease (27 SS, nine SC, and one S-beta-thalassemia) of 477 unrelated sickle cell patients where the beta3 gene was linked to 20 different atypical haplotypes. These atypical chromosomes account for about 5% of the overall betaS chromosomes in this population. To investigate the origin of these atypical betaS haplotypes, we performed extensive typing of betaS and betaA chromosomes. Twenty-two different 5' subhaplotypes were identified among the betaS chromosomes. Fifteen of 20 different atypical haplotypes are likely to be the product of recombination by a single crossover around the <
Assuntos
Haplótipos/genética , Hemoglobina Falciforme/genética , Coleta de Dados , Variação Genética , Guadalupe/epidemiologia , Humanos , Mapeamento por RestriçãoRESUMO
This prospective study examined the prevalence, clinical features, and risk factors of osteonecrosis of the femoral head among adult sickle cell disease patients in Guadeloupe. Screening of osteonecrosis of the femoral head was performed using radiography, bone scintigraphy, and tomodensitometry. One hundred thirteen adults with sickle cell disease (67 SS and 46 SC patients) comprised the study population. Forty-two (37.2%) patients had osteonecrosis of one or both hips (67 [29.6%] hips) without association to a particular genotype, although bilateral involvement was more frequent among SS patients. While the prevalence of femoral head osteonecrosis increased with age, patients of all ages were affected, particularly young SC adults. Osteonecrosis of the femoral head was diagnosed at preradiographic stages (stage I) in 30% of hips and was frequently asymptomatic (60% of all cases; 95% and 90% of stages I and II, respectively). Osteonecrosis of the femoral head was significantly associated with a history of leg ulcer and osteonecrosis of the humeral head. SS patients with higher hemoglobin levels had an increased risk of osteonecrosis of the femoral head.
Assuntos
Anemia Falciforme/epidemiologia , Necrose da Cabeça do Fêmur/epidemiologia , Adulto , Distribuição por Idade , Anemia Falciforme/diagnóstico , Comorbidade , Intervalos de Confiança , Feminino , Necrose da Cabeça do Fêmur/diagnóstico , Guadalupe/epidemiologia , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Prevalência , Estudos Prospectivos , Fatores de Risco , Distribuição por SexoAssuntos
Hemoglobinopatias/genética , Mutação , Talassemia beta/genética , Adolescente , Adulto , Criança , Etnicidade , Triagem de Portadores Genéticos , Guadalupe , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/prevenção & controle , Humanos , Incidência , Programas de Rastreamento , Mutação Puntual , Talassemia beta/epidemiologia , Talassemia beta/prevenção & controleRESUMO
We have studied haplotype of beta(S) chromosome and alpha-globin gene status in 534 patients (255 adults and 279 children of whom 159 neonates) from Guadeloupe with various sickle cell-related conditions, namely SS (n = 298), SC (n = 170), S-beta-thal (n = 56), and other rare forms (n = 10). Haplotype data on beta(S) chromosomes confirm our previous observation that Benin type is the most prevalent (75%) beta(S) chromosome in Guadeloupe, in disagreement with the historical records. Comparison of the frequency of distribution of various beta(S) haplotypes between neonates and adults on the one hand and between SS and SC cases on the other shows that the current beta(S) haplotype distribution in this island is not distorted by haplotype-related differential survival. We also show that the frequency of alpha-thalassemia (-3.7 kb) in Guadeloupe is one of the highest recorded in this region involved in Atlantic slave trade and also failed to reveal any age-dependent increase in frequency. We conclude that the African component of Guadeloupe is distinct from that of Brazil and Cuba but is close to that of Jamaica.
Assuntos
Anemia Falciforme/genética , Globinas/genética , Talassemia alfa/genética , Adulto , Cuba , Guadalupe , Haplótipos , Humanos , Recém-NascidoRESUMO
As in most caribbean countries, Sickle Cell Disease (SCD) is a major public health problem in Guadeloupe. A prenatal counselling program was developed, at an early stage of pregnancy, for at-risk couples. Over a 6 year period, 144 couples at-risk of having a child with homozygous sickle cell (SS: n = 103) or sickle cell C disease (SC: n = 41) were seen for prenatal counselling. Among those belonging to the SS risk group, 64 (62%) underwent prenatal diagnosis (PND), which allowed identification of 27 SS fetuses, with an induced abortion rate of 70%. Among those of the SC risk group, 14 (34%) accepted PND and the diagnosis of SC was made in 5 cases with an induced abortion rate of 60%. Factors, appeared to play a role in seeking PND and induced abortion, were the type of risk (SS or SC), multiparity, existence of affected child in the family and gestational age at the time of counselling. Our experience reveals that, an early prospective identification of at-risk couples combined with education to increase the awareness of the problem at the individual and population level need to be achieved to further improve the efficiency of our prevention program.
Assuntos
Anemia Falciforme/genética , Aconselhamento Genético , Aborto Induzido , Feminino , Guadalupe , Hemoglobinas/genética , Humanos , Gravidez , Estudos RetrospectivosRESUMO
In order to perform genetic counselling and prenatal diagnosis of Hb-S-beta-thalassemia disease and beta-thalassemia, we have delineated the spectrum of beta-thalassemia alleles in the Guadeloupean population. A sample of 63 unrelated families was analyzed including 70 beta-thalassemia carriers, 52 Hb-S-beta-thalassemia, and 8 patients with different beta-thalassemic hemoglobinopathies. Among the eleven mutations identified, four of them [-29 (A --> G), IVS-I-5 (G --> A), IVS-II-1 (G --> A), and IVS-I-5 (G --> C)] account for 77.6% of the beta-thalassemia chromosomes present in the studied families. The seven other variants, CD 24 (T --> A), IVS-I-2 (T --> C), Poly A (T --> C), -88 (C --> T), IVS- 11-849 (A --> G), Hb E, and Hb Lepore are less frequent. As a result, Hb S-beta+-thalassemia type 1 (low Hb A values: 5-15%) together with Hb S-beta(omicron)-thalassemia phenotypes are as frequent as Hb S-beta+-thalassemia type 2 (high Hb A values: 20-30%) in the Guadeloupean population. Patients with Hb S-beta+-thalassemia type 2 have milder hematological manifestations of the disease compared to patients with Hb S-beta(omicron)-thalassemia and Hb S-beta+-thalassemia type 1. This first report on the type and nature of beta-thalassemia mutations in Guadeloupe shows that prenatal diagnosis of Hb S-beta-thalassemia and beta-thalassemia should be feasible by direct detection of point mutation in most cases.
Assuntos
Globinas/genética , Talassemia beta/genética , África Ocidental/etnologia , Alelos , Anemia Falciforme/epidemiologia , Anemia Falciforme/etnologia , Anemia Falciforme/genética , Frequência do Gene , Aconselhamento Genético , Guadalupe/epidemiologia , Hemoglobina Falciforme/genética , Humanos , Índia/etnologia , Região do Mediterrâneo/etnologia , Traço Falciforme/complicações , Traço Falciforme/epidemiologia , Traço Falciforme/etnologia , Traço Falciforme/genética , Talassemia beta/complicações , Talassemia beta/epidemiologia , Talassemia beta/etnologiaRESUMO
The beta gene cluster haplotypes, alpha gene status, Hb F level and hematological parameters have been characterized in 154 unrelated Guadeloupe patients with sickle cell disease: 112 with sickle cell anemia, 26 with SC disease, 15 with Hb S-beta-thalassemia, and one patient with Hb S in association with the hereditary persistence of fetal hemoglobin. Fourteen haplotypes in 16 combinations were found, the three major African haplotypes were present on 92% of all chromosomes: 73% Benin, 11% Bantu, 8% Senegal. Among SS patients, 57% were Benin homozygotes, one patient was a Senegal homozygote, one patient was a Bantu homozygote, and all the others were heterozygous. The A gamma T chain was observed on seven chromosomes and about 5% of the analyzed beta S chromosomes exhibited atypical haplotypes. The common haplotype beta C was found in all patients with SC disease. An interesting feature was the high frequency (44%) of deletional alpha-thalassemia among SS patients. Two patients have an alpha-gene globin triplication. The DNA haplotypes and alpha-gene status have been correlated with hematological parameters in these patients. The anthropological aspect of these data is interesting as the haplotypes of the beta-globin gene throw light on the slave trade from the various parts of Africa to the Caribbean Islands in particular, and North America in general.
Assuntos
Anemia Falciforme/genética , Hemoglobina Fetal/metabolismo , Globinas/química , Globinas/genética , Adolescente , Criança , Feminino , Guadalupe , Haplótipos , Testes Hematológicos , Humanos , Masculino , Família Multigênica , Talassemia alfa/genéticaRESUMO
In order to delineate the spectrum of á-thalassaemia (á-thal) mutations in the Guadeloupean population, we have analysed a representative sample of 59 unrelated families carrying a á-thalassaemia trait. Using gene amplification, hybridization with 32P-labelled oligonucleotide probes and sequencing of amplified DNA, 8 different á-thal mutations were identified in 62 members of 36 families. Four of these families carried a á§-thal trait whereas, in the 32 others, a á+-thal trait has been identified. All patients were á-thal heterozygous: 30 had Hb S/á-thal, 1 had Hb C/á-thal, 1 had HPFH/á-thal whereas the remaining 30 had a Hb A/á-thal genotype. Four of the á-thal mutations detected [-29 (A -> G), IVS-I-5 (G -> C), IVS-II-1 (G -> A) and CD 24 (T -> A)] accounted for approximately 88.8 percent of the á-thalassaemia chromosomes identified. The four other variants, -88 (C -> T), IVS-I-5 (G -> A), IVS-I-5 (G -> T) and IVS-I-2 (T -> C), are less frequent. The á-thalassaemia mutations in 23 families remained unidentified and are under investigation. This study provides data for prenatal diagnosis of sickle-cell disease for Hb S/á-thalassaemia genotypes (AU)
Assuntos
Humanos , Masculino , Feminino , Talassemia beta/genéticaRESUMO
A sample of 42 unrelated sickle cell (SS) patients were randomly selected from regular attenders at the paediatric services of the Pointe-a-Pitre Hospital. á gene cluster and O gene haplotypes were determined by Southern blotting. Twelve á haplotypes in 12 combinations were found for the 84 ás chromosomes studied. The most common were Benin (63 per cent), Bantu (12 per cent) and Senegal (11 per cent) types which accounted for 87 per cent of all chromosomes. About 13 per cent of the ás chromosomes analysed had atypical haplotypes. Much the same diversity was observed for the ás gene in Jamaicans and Black patients in the USA. An interesting feature was the high (46 per cent) gene frequency of deletional O thalassemia. One patient had the O gene globin triplication. The frequency of (-O) was 0.24, and there is no evidence that this frequency differs from one á-haplotype to another. No clear correlations could be made between the haemoglobin level, haematological parameters and á haplotype status in this study because of the large number of variables and small sample size. From the anthropological aspect, haplotyping may shed light on the slave trade from various parts of Africa to the Caribbean (AU)