The impact of clinical genome sequencing in a global population with suspected rare genetic disease.

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9-3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1-∞, p = 0.05) and change of management (OR 0.9, 95% CI 0.5-1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities.

Sickle cell anemia and pregnancy: Profile of hemodynamic changes in sickle cell pregnant women in Kinshasa.

Pregnancy is accompanied by hormonal changes. These relate mainly to progesterone and placenate growth factor. Hemodynamic changes are also observed. in a sickle cell pregnant woman, all these changes have a direct effect on hypoxia. This is responsible for the polymerization of HbS. The latter causes the sickling of sickle red blood cells. sickling of red blood cells is responsible for hemolysis and vasoocclusion, two major acute manifestations during pregnancy in a sickle cell patient.

Clinical and biological profile of Sickle Cell Anemia children in a rural area in Central Africa.

BACKGROUND: Sickle Cell Anemia (SCA) is the most common genetic disease worldwide caused by a single mutation in the gene HBB. The disease severity is very variable and depends on many factors. We evaluated the clinical and biological profile of sickle cell anemia children in rural Central Africa. METHODS: This cross-sectional study was conducted in the Hôpital Saint Luc de Kisantu, located 120 km away from Kinshasa-DR Congo in an area of 35 km around Kisantu with a population of roughly 80 000 individuals. We included SCA patients aged 6 months to 18 years. We collected clinical and hematological data. The SCA scoring system proposed by Adegoke et al. in 2013 was applied to determine the disease severity. We searched for factors associated to the disease severity. RESULTS: This study included 136 patients, 66 males and 70 females (sex-ratio M/F 0.94). The mean severity score was 8.21 ± 5.30 (ranges 0-23). Fifty-nine (43.4%) children had mild disease, 62 (45.6%) moderate and 15 (11%) severe disease. Girls had higher levels of HbF than boys (p = 0.003). An inverse correlation was observed between fetal hemoglobin and the disease severity (p = 0.005, r -0.239, IC95% -6.139; -1.469). Some factors such age influence the occurrence of certain chronic complications such as avascular bone necrosis. CONCLUSION: In conclusion, the disease severity of SCA depends on multiple factors. In this study, fetal hemoglobin was the main modulator of the disease severity. These data may also serve as a baseline to initiate HU treatment in this setting.

Déterminants du carcinome photo-induit chez les sujets de phototype albinos aux Cliniques Universitaires de Kinshasa / Determinants of photo-induced carcinoma in albino phototype people at the Kinshasa University hospital

Contexte et objectif. Les rayonnements ultra-violets constituent un facteur connu de risque de carcinome photo-induit chez l'albinos en milieu à fort ensoleillement. La présente étude a évalué l'ampleur du carcinome photo induit et a recherché les principaux déterminants chez les sujets de phototype albinos à Kinshasa. Méthodes. Dans une étude transversale, des sujets de phototype albinos recrutés de manière consécutive, ont été examinés du 1er janvier 2020 au 30 septembre 2020 au Service de dermatologie des Cliniques Universitaires de Kinshasa. La fréquence du carcinome a été estimée et ses déterminants recherchés à l'aide d'une analyse de régression logistique. Résultats. Au total 100 albinos ont été inclus. Près d'un albinos sur deux (44 %) a développé un carcinome. En analyse multivariée, l'âge >30 ans (OR : 2,68 ; IC 95% :1,65-11,10 ; p=0,017), la présence des kératoses actiniques (OR: 3.80; IC 95%: 1.43-7.23; p=0.023), un antécédent familial de cancer non cutané (OR : 2,40 ; IC95% : 1,47-12,35 ; p=0,29), un antécédent familial de carcinome (OR : 4,99 ; IC95% :3,0-9,29 ;p=0,000) et un antécédent personnel de polytransfusion (OR :2,30 ; IC 95% :1,26-6,20 ;p=0,045) ont été identifiés comme les principaux déterminants du carcinome photo-induit. Conclusion. Près d'un albinos sur deux présente un carcinome photo-induit. Ceci justifie l'intensification des mesures comportementales et préventives contre le développement des cancers cutanés ciblant particulièrement les albinos âgés de moins de 30 ans, présentant des kératoses actiniques et ceux avec antécédents familiaux de cancer (carcinome et autres).

Clinical and laboratory characterization of adult sickle cell anemia patients in Kinshasa.

BACKGROUND: Sickle cell anemia (SCA) is a monogenic hemoglobinopathy associated with severe acute and chronic complications, with the highest incidence worldwide in Sub-Saharan Africa. The wide variability in clinical manifestations suggest that a uniform response to hydroxurea may not be attained. In view of a potential treatment with hydroxyurea (HU), we assessed the variability of clinical and hematological manifestations in a cohort of adults with SCA in Kinshasa, capital of the DR Congo in Central Africa. METHODS: A cross-sectional study was conducted in a hospital dedicated to SCA management in Kinshasa. Clinical history of patients was recorded, a complete physical examination performed. The diagnosis was confirmed by means of DNA analysis. A full blood count and hemolysis markers were measured. The severity of the disease was evaluated by means of a previously reported score. RESULTS: The study group consisted of 166 genetically confirmed SCA patients. The SCA severity was mild in 28.9%, moderate in 64.5% and severe in 6.6%. The disease severity score increased with patient's age (p ≤ 0.001). The severity was higher in males compared to females (p = 0.012). In males, the severity score was correlated with the presence of priapism (p = 0.045), a manifestation not previously incorporated in the severity score. The severity score was inversely correlated with the fetal hemoglobin (HbF) rate (p = 0.005). Malnutrition (BMI <18.5 kg/m2) was present in 47% of patients and was related to the male sex, hip disease (aOR 3.11; p = 0.019) and severe phenotype (aOR 3.53; p = 0.012). Leg ulcers were more frequent in males than in females (p = 0.001; OR 24.3) and were correlated with the number of days of hospitalization (p = 0.029). Hip disease was related to the increasing age (p = 0.008). CONCLUSION: In this selected, hospital-based populations of adults with SCA, severe disease was rare, which may be due to survival bias. However, two thirds had moderate severity of the disease, mostly with a low HbF, and they may benefit from HU treatment. In the Central-African setting the separation between vaso-occlusive and hyperhemolytic sub-phenotypes was not applicable.

Sickle cell disease and pregnancy profile of complicated malaria in 982 pregnancies in Kinshasa.

INTRODUCTION: Malaria is associated with high morbidity during pregnancy. Homozygous sickle cell pregnant women are even more exposed during complicated malaria. The objective of the study was to evaluate the maternal and fetal morbidity of homozygous sickle cell pregnant pregnant women with complicated malaria. METHODS: We conducted a retrospective case-control study of 982 pregnancies in sickle cell pregnant women, during which a group of sickle cell pregnant women who received antimalarial chemoprophylaxis was compared to another group without chemoprophylaxis. We analyzed the clinical evolution of pregnant women (VOCs and transfusions, pregnancy weight gain) and parasite (parasite density at the time of diagnosis of complicated malaria and during treatment for three days). We analyzed the parameters of newborns at birth (age of pregnancy at the time of delivery, birth weight, weight of the placenta and histopathological examination of the placenta. RESULTS: Out of 982 pregnancies, 15% of pregnant women suffered from complicated malaria, 57% suffered from uncomplicated malaria and 28% did not suffer from malaria. Pregnancy weight gain, birth weight, was better in the group of pregnant women who received chemoprophylaxis and the placenta had less histological lesions. Parasite density was low. There was a significant positive correlation between parasite density and the number of CVOs and transfusions and between parasite density and histological lesions of the placenta and low birth weight. CONCLUSION: Complicated malaria is associated with high maternal and fetal morbidity in sickle cell patients. Malaria chemoprophylaxis can reduce maternal and fetal complications and parasite density during malaria infection.

Objective evaluation of facial features in Congolese newborns by facial measurements. The need for population-specific measurements.

The evaluation of dysmorphism is often subjective because many continuous traits are not easily measured or lack normal values. Because many common morphologic profiles vary between populations, population-specific reference ranges of relevant traits are needed. We aim to evaluate the objective assessment of facial dysmorphism in 553 Congolese newborns based on facial measurements. Measurements taken with a ruler were on average larger compared to those with a caliper, but the bias did not depend on the size of the measurement. We therefore introduced a correction factor that allows to use both techniques for facial measurements interchangeably in future studies. The outer canthal distance, palpebral fissure length, and mouth width were significantly larger in Congolese newborns (respectively mean 6.59 [SD 0.48]; mean 2.20 [SD 0.24]; mean 2.78 [SD 0.26]) when compared to references based on European newborns (respectively mean 3.59 [SD 1.76]; mean 4.20 [SD 2.26]; mean 0.47 [SD 1.21]), while the rest of measurements were significantly smaller. The interpupillary distance (IPD) calculated from inner canthal distance and outer canthal distance was not significantly different. We observed a poor agreement between clinical evaluation and measured features (kappa of 0.432). Clinicians were more likely to recognize a face as having wide-spaced eyes when it had been recognized as such during the clinical examination, more than if the child had a high interpupillary distance. This suggests that the measured IPD is not precisely reflecting what is clinically evaluated as wide-spaced eyes.

PERCHING syndrome: Clinical presentation in the first African patient confirmed by clinical whole genome sequencing.

PERCHING syndrome is a rare multisystem developmental disorder caused by autosomal recessive (AR) variants (truncating and missense) in the Kelch-like family member 7 gene (KLHL7). We report the first phenotypic and molecular description of PERCHING syndrome in a patient from Central Africa. The patient presented multiple dysmorphic features in addition to neurological, respiratory, gastroenteric, and dysautonomic disorders. Clinical Whole Genome Sequencing in the proband and his mother identified two novel heterozygous variants in the KLHL7 gene, including a maternally inherited intronic variant (NM_001031710.2:c.793 + 5G > C) classified as Variant of Uncertain Significance and a frameshift stop gain variant (NM_001031710.2:c.944delG; p.Ser315ThrfsTer23) of unknown inheritance classified as likely pathogenic. Although the diagnosis was only evoked after genomic testing, the review of published patients suggests that this disease could be clinically recognizable and maybe considered as an encephalopathy. Our report will allow expanding the phenotypic and molecular spectrum of Perching syndrome.

DNA testing for sickle cell anemia in Africa: Implementation choices for the Democratic Republic of Congo.

BACKGROUND: Hemoglobin-based tests form the reference diagnostic test for SCA. In limited resource countries, these tests face limitations including cost, low sensitivity due to recurrent transfusions in endemic malaria region, and interference from fetal hemoglobin in neonatal diagnostic. This study aimed at adapting DNA-based SCA tests to limited resource countries and evaluating the economic benefit. METHODS: 338 participants were recruited in the Democratic Republic of Congo, sorted in 3 cohorts based on venous blood, umbilical cord blood (UCB) and buccal swab sampling. RFLP was performed to identify mutated allele. The feasibility and technical validity of this RFLP was evaluated for specimens collected on DBS cards and on EDTA tubes. RFLP on DBS stored at room temperature was regularly repeated to assess sample conservation. Finally, the cost analysis was performed. RESULTS: DBS cards yielded identical results to extracted DNA. Repeated testing returned the same result after four years. The DBS-based test performed on UCB or on buccal swab had a sensitivity and a precision of 100%. Cost comparison indicated that our approach costs half price of the widely used isoelectrofocussing of hemoglobin. CONCLUSION: The implemented DNA-based test approach overcomes the limitations faced by hemoglobin-based tests, while being more affordable. We propose to implement the RFLP test as a first line diagnostic test after transfusion and as second tiers for newborn screening. However, users should be aware that this test is unable to differentiate HbC from HbS or identify other point mutation of gene deletion of HBB gene.

Clinical presentation and evolution of Xia-Gibbs syndrome due to p.Gly375ArgfsTer3 variant in a patient from DR Congo (Central Africa).

Xia-Gibbs syndrome (XGS) is a very rare genetic condition. The clinical spectrum is very broad and variable. The phenotype and evolution in a Congolese boy with XGS have been reported. At 6 years he had speech delay, drooling, marked hyperactivity, attention deficit, aggressive behavior, and intellectual disability. Dysmorphological evaluation revealed strabismus, mild unilateral ptosis, uplifted ear lobes, flat philtrum, thin upper lip vermillion, high arched palate, and flat feet. Patient-only whole exome sequencing identified a known pathogenic frameshift variant in the AHDC1 gene [NM_001029882.3(AHDC1):c.1122dupC;(p.Gly375ArgfsTer3)]. The clinical follow-up revealed the deterioration of his fine motor skills and significant cerebellar phenotype including tremor, pes cavus, and gait instability at the age of 12 years. This patient was compared with three previously reported patients with the same variant but did not identify a consistent pattern in the evolution of symptoms with age.

Phenotype and growth in Sotos syndrome patient from DR Congo (Central Africa).

Sotos syndrome is a widely studied overgrowth syndrome. Clinical presentation includes excessive growth during childhood, macrocephaly, learning difficulties of various degrees, variable minor features, and distinctive facial gestalt. We provide in this report the first phenotypic and growth description of Sotos syndrome in a patient from Central Africa. At 6 month the patient exhibited axial hypotonia, delayed speech development and dysmorphism including long face, sparse eyebrows, hypertelorism, malar hypoplasia and dark flushing, short philtrum, depressed nasal root, anteverted nares, thick upper and lower lip vermilions, macroglossia, prominent forehead, large and peculiar ears, wide intermammillary distance, deep palmar creases, dysplastic finger nails, partial syndactyly of toes, broad, and overlapping hallux. At 19 months, malar flushing became reddish and a retraction of the middle of the lower lip was observed, resembling a bifid lip. He retained the same clinical features at 31 months. Head circumference, weight, and height where within normal ranges at birth but became all above 97th centiles at 4 months. The height velocity evolved in three phases starting with a very fast growth from birth to 6 months (54 cm/year), then a fast phase from 6 to 16 months (18 cm/year) and a slow phase from 16 to 31 months (4.8 cm/year). Conversely, the patient exhibited an acceleration of weight after the first year of life. Our patient exhibited very prominent lips and deep philtrum, which are common facial traits in African individuals. The current report shows an admixture of ethnic-specific features with syndrome-specific features in an African patient.

Exploring association between MBL2 gene polymorphisms and the occurrence of clinical blackwater fever through a case-control study in Congolese children.

BACKGROUND: Blackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often leading to acute renal failure. Thus far, the genetics of the underlying susceptibility to develop BWF is not fully elucidated. Deficiency in the MBL protein, an important component of the innate immune system, has previously been suggested to be a susceptibility factor for the development of severe malaria. This study aimed to evaluate the association between MBL2 gene polymorphisms, known to affect the MBL protein level/activity, and the occurrence of BWF among Congolese children. METHODS: This is a case-control study. Cases were patients with BWF, whereas controls, matched for gender and age, had uncomplicated malaria (UM). Dried blood spot was collected for genotyping. RESULTS: A total of 129 children were screened, including 43 BWF and 86 UM. The common allele in BWF and UM was A, with a frequency of 76.7 and 61.0%, respectively (OR: 2.67 (0.87-829) and p = 0.079). The frequency of the C allele was 18.6 and 29.1% in BWF and UM groups, respectively, with p = 0.858. Not a single D allele was encountered. Genotype AA was at higher risk for BWF whereas genotypes A0 (AB and AC) were over-represented in UM group (OR: 0.21 (0.06-0.78)) with p = 0.019. Nine haplotypes were observed in this study: 3 high MBL expression haplotypes and 6 low MBL expression haplotype. One new haplotype HYPC was observed in this study. None of these haplotypes was significantly associated with BWF. CONCLUSION: This pilot study is a preliminary research on MBL2 gene and infectious diseases in DRC. The study results show a higher risk for BWF in AA. This suggests that future studies on BWF should further investigate the contribution of a strong immune response to the occurrence of BWF.

Microdeletion of the entire IRF6 gene in a Subsaharian African's family with Van der Woude syndrome.

Microdeletion of the entire interferon regulatory factory 6 (IRF 6) gene is a rare cause of Van der Woude syndrome (VDW) with only few cases reported in medical literature. Its occurrence in multiple affected members of a family is exceptional. The aim of this presentation was to describe a Central African family with typical VDW phenotype carrying an IRF6 gene deletion. Here we reported phenotype features of members of a Central African family with VDW syndrome consisting of labioalveolar cleft, depressions of the lower lip with labial fistulae (lip pits), submucosal clefts and cleft palate. Mutation analysis by means of multiplex ligation-dependent probe amplification and chromosomal microarray revealed a 374.070 kb, deletion encompassing the entire IRF6 gene in four affected family members. Microdeletion of the entire IRF6 gene causes the classical VDW syndrome phenotype.

Missense variants in TAF1 and developmental phenotypes: challenges of determining pathogenicity.

We recently described a new neurodevelopmental syndrome (TAF1/MRXS33 intellectual disability syndrome) (MIM# 300966) caused by pathogenic variants involving the X-linked gene TAF1, which participates in RNA polymerase II transcription. The initial study reported eleven families, and the syndrome was defined as presenting early in life with hypotonia, facial dysmorphia, and developmental delay that evolved into intellectual disability (ID) and/or autism spectrum disorder (ASD). We have now identified an additional 27 families through a genotype-first approach. Familial segregation analysis, clinical phenotyping, and bioinformatics were capitalized on to assess potential variant pathogenicity, and molecular modelling was performed for those variants falling within structurally characterized domains of TAF1. A novel phenotypic clustering approach was also applied, in which the phenotypes of affected individuals were classified using 51 standardized Human Phenotype Ontology (HPO) terms. Phenotypes associated with TAF1 variants show considerable pleiotropy and clinical variability, but prominent among previously unreported effects were brain morphological abnormalities, seizures, hearing loss, and heart malformations. Our allelic series broadens the phenotypic spectrum of TAF1/MRXS33 intellectual disability syndrome and the range of TAF1 molecular defects in humans. It also illustrates the challenges for determining the pathogenicity of inherited missense variants, particularly for genes mapping to chromosome X. This article is protected by copyright. All rights reserved.

Homozygous Deletion Alpha-Thalassemia and Hereditary Persistence of Fetal Hemoglobin, Two Genetic Factors Predictive the Reduction of Morbidity and Mortality During Pregnancy in Sickle Cell Patients. A Report from the Democratic Republic of Congo.

OBJECTIVE: to determine the beneficial role of Fetal Hemoglobin (FHb) and alpha-thal on fetal and maternal morbidity during pregnancy in sickle cell patients. STUDY SITE: the study was conducted at the sickle cell center of Kinshasa between 2008 and 2018. SETTING AND STUDY POPULATION: this is a documentary and analytical study that included 980 deliveries of homozygous sickle cell patients. METHODS: the diagnosis of SCD and the quantification of FHb were performed with the capillary electrophoresis technique. The molecular test confirmed the diagnosis of SCD. The diagnosis of alpha-thal was made with the multiplex ligation-dependent probe amplification (MLPA) technique. Sickle cell pregnancies were followed according to the protocol of care in force in the University of Kinshasa Hospital service. The variables of interest were: hematological variables, sickle cell crises during pregnancy, maternal and fetal complications. STATISTICS: statistical analyses were performed with SPSS 20.0 software. Means and standard deviations were compared with the Student's t and ANOVA tests. The value of p <0.05 was considered the significance level. RESULTS: the Hb-SS / alpha-thal and HbSS / HPFH genotypes were observed in 101 and 121 women, respectively. Otherwise, 758 women had HbSS genotype. The morbidity related to sickle cell complications in the mother and fetus were less frequent in the Hb-SS / alpha-thal and HbSS / HPFH groups than in HB-SS group. The differences were statistically significant. CONCLUSION: this study showed a significant protective effect of alpha-thal and HPFH during pregnancy in sickle-cell pregnant women.

Usefulness of fragile X checklist and CGG distribution in specialized institutions in Kinshasa, DR Congo.

Screening for fragile X syndrome (FXS) is essential in children with developmental delay or intellectual disability (ID). In addition, using clinical screening checklists remains of high interest in resource-limited settings. We aimed to gain insight into the prevalence of FXS and the distribution of CGG alleles and to evaluate the usefulness of three checklists in specialized institutions in Kinshasa, DR Congo. We recruited 80 males and 25 females from six specialized institutions in Kinshasa and administered a questionnaire comprising items from the following FXS checklists: Hagerman, Maes, and Guruju. FMR1 CGG repeats were assessed for every patient. About 37% of patients were referable for FX testing based on Hagerman's checklist, 35% for Maes', and 43.80% for Guruju's, but none of them was molecularly confirmed to have FXS. Thus, specificities were 62.86, 64.76, and 56.5%, respectively, for Hagerman, Maes, and Guruju, respectively. The mean CGG allele size was 28.55 ± 2.83 (ranges, 17-48). The 29 CGG was the most frequent allele (24.61%). Thus, existing checklists should not be automatically applied to Congolese patients without adjustments. The distribution of CGG repeats and the number of CGG alleles are similar to other African studies.

A comprehensive clinical and genetic study in 127 patients with ID in Kinshasa, DR Congo.

Pathogenic variants account for 4 to 41% of patients with intellectual disability (ID) or developmental delay (DD). In Sub-Saharan Africa, the prevalence of ID is thought to be higher, but data in Central Africa are limited to some case reports. In addition, clinical descriptions of some syndromes are not available for this population. This study aimed at providing an estimate for the fraction of ID/DD for which an underlying etiological genetic cause may be elucidated and provide insights into their clinical presentation in special institutions in a Central African country. A total of 127 patients (33 females and 94 males, mean age 10.03 ± 4.68 years), were recruited from six institutions across Kinshasa. A clinical diagnosis was achieved in 44 but molecular confirmation was achieved in 21 of the 22 patients with expected genetic defect (95% clinical sensitivity). Identified diseases included Down syndrome (15%), submicroscopic copy number variants (9%), aminoacylase deficiency (0.8%), Partington syndrome in one patient (0.8%) and his similarly affected brother, X-linked syndromic Mental Retardation type 33 (0.8%), and two conditions without clear underlying molecular genetic etiologies (Oculo-Auriculo-Vertebral and Amniotic Bands Sequence). We have shown that genetic etiologies, similar to those reported in Caucasian subjects, are a common etiologic cause of ID in African patients from Africa. We have confirmed the diagnostic utility of clinical characterization prior to genetic testing. Finally, our clinical descriptions provide insights into the presentation of these genetic diseases in African patients.

Non-syndromic cleft lip and/or cleft palate: Epidemiology and risk factors in Lubumbashi (DR Congo), a case-control study.

PURPOSE: To determine the incidence and risk factors of occurrence of non-syndromic cleft lip and/or cleft palate (NSCLP) in Lubumbashi. METHOD: A case-control study was conducted in the health district of Lubumbashi from February 2012 to December 2015. An exhaustive sampling, collecting all newborns with cleft lip and/or cleft palate (CL ± P) in maternity wards was conducted. From a total of 172 cases, 162 non-syndromic cases were recruited. For each case, one clinically normal newborn control was selected. RESULTS: NSCLP had an incidence of 1/1258 live births (0.8/1000). We found significant associations with a family history of cleft lip and palate (CLP) (x2family history = 11.5, p = 0.0007), maternal alcohol intake (OR = 19.3, 95% CI: 1.9-197.1), paternal alcohol during the periconceptional period and the first trimester of pregnancy (OR = 18.7, 95% CI: 3.9-89.2), maternal educational level lower than high school (OR = 9.5, 95% CI: 2.0-44.7), clay (Pemba) consumption during pregnancy (OR = 38.3, 95% CI: 9.3-157.0), the use of insecticides in the evening (OR = 130.3, 95% CI: 13.2-1286.9), indoor cooking with charcoal (Makala) (OR = 6.5, 95% CI: 1.22-34.5), and regular consumption of Kapolowe fish, supposedly contaminated with heavy metals (OR = 29.5, 95% CI: 7.4-116.7). CONCLUSION: Several environmental risk factors highly prevalent in Central Africa for facial clefting were found.

Protective BCL11A and HBS1L-MYB polymorphisms in a cohort of 102 Congolese patients suffering from sickle cell anemia.

BACKGROUND: We aimed to investigate the distribution of selected BCL11A and HMIP polymorphisms (SNP's), and to assess the correlation with HPFH in a cohort of sickle cell patients. METHODS: A preliminary cross-sectional study was conducted in 102 patients. Group 1 was composed of patients with HPFH and Group 2 consisted of patients without HbF. We assessed 8 SNPs previously associated with HPFH in cohorts genetically close to the Congolese population. Observed frequencies were compared to expected frequencies. RESULTS: In the group 1, at rs7606173, the observed frequency for the genotype GG was significantly higher and the genotype GC was significantly lower than their respective expected frequencies. At rs9399137, the observed frequency of the genotype TT was significantly lower than expected. Conversely, the observed frequency of the genotype TC was significantly higher than expected. The observed frequency of the genotype TT at rs11886868 was significantly lower than the expected whereas the frequency of the genotype TC was significantly higher than observed. The lowest HbF level was recorded in patients with genotype CC at rs11886868. CONCLUSION: In this preliminary study, the results demonstrate that alleles of some of the 8 studied SNPs are not randomly distributed among patients with or without HPFH in this cohort.