RESUMO
BACKGROUND: Iron deficiency (ID) with or without anemia is associated with impaired mental and psychomotor development. Given the paucity of information on physicians' knowledge and practices on iron (Fe) supplementation and impact of ID in the Middle East and North Africa, it was felt important to conduct a survey. METHOD: A group of expert physicians developed a questionnaire that was randomly distributed among Middle East and North Africa doctors to assess their knowledge and practices on introduction of complementary feeding, impact of ID, its prevention, and their impression on prevalence of ID. Descriptive statistics were used. RESULTS: We received 2444 completed questionnaires. Thirty-nine percent of physicians do not follow the European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines regarding age of introduction of complementary feedings. Approximately 62% estimate the prevalence of ID anemia to be 40% to 70%; however, only 17% always monitor hemoglobin between 9 and 12 months of age, 43% do so "almost" always, whereas 36% do so "rarely" or (4%) "never." For the prevention of ID in infants older than 6 months of age, almost all recommend introducing Fe supplements. Ninety-seven percent agree that untreated ID during infancy may have long-term negative effects on cognitive function, whereas 53.26% consider that Fe-enriched infant cereals result in staining of the baby teeth, constipation, and dark stools. CONCLUSIONS: Although there is awareness of the impact of ID, there are some misconceptions regarding age of introduction of complementary feedings, surveillance of Fe status, and side effects of Fe-enriched infant cereals. There is a need for educational initiatives focusing on prevention of Fe deficiency.
Assuntos
Anemia Ferropriva/prevenção & controle , Comportamento Alimentar/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Fenômenos Fisiológicos da Nutrição do Lactente , Médicos/psicologia , África do Norte , Anemia Ferropriva/psicologia , Suplementos Nutricionais , Feminino , Humanos , Lactente , Ferro/sangue , Deficiências de Ferro , Masculino , Oriente MédioRESUMO
BACKGROUND: The majority of cleft lip with or without cleft palate cases appear as an isolated, nonsyndromic entity (NSCLP). With the advent of next generation sequencing, whole exome sequencing (WES) has been used to identify single nucleotide variants and insertion/deletions which cause or increase the risk of NSCLP. However, to our knowledge, there are no published studies using WES in NSCLP to investigate copy number changes (CNCs), which are a major component of human genetic variation. Our study aimed to identify CNCs associated with NSCLP in a Honduran population using WES. METHODS: WES was performed on two to four members of 27 multiplex Honduran families. CNCs were identified using two algorithms, CoNIFER and XHMM. Priority was given to CNCs that were identified in more than one patient and had variant frequencies of less than 5% in reference data sets. RESULTS: WES completion was defined as >90% of the WES target at >8 × coverage and >80% of the WES target at >20 × coverage. Twenty-four CNCs that met our inclusion criteria were identified by both CoNIFER and XHMM. These CNCs were confirmed using quantitative PCR. Pedigree analysis produced three CNCs corresponding to ADH7, AHR, and CRYZ segregating with NSCLP. Two of the three CNCs implicate genes, AHR and ADH7, whose known biological functions could plausibly play a role in NSCLP. CONCLUSION: WES can be used to detect candidate CNCs that may be involved in the pathophysiology of NSCLP. Birth Defects Research 109:1257-1267, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Adolescente , Adulto , Álcool Desidrogenase/genética , Álcool Desidrogenase/metabolismo , Alelos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Criança , Pré-Escolar , Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Variações do Número de Cópias de DNA , Família , Feminino , Frequência do Gene , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Honduras/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Polimorfismo de Nucleotídeo Único/genética , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Sequenciamento do Exoma/métodosRESUMO
OBJECTIVES/HYPOTHESIS: A candidate variant (p.Val496Ala) of the ACSS2 gene (T > C missense, rs59088485 variant at chr20: bp37 33509608) was previously found to consistently segregate with nonsyndromic cleft lip and/or palate (NSCLP) in three Honduran families. Objectives of this study were 1) to investigate the frequency of this ACSS2 variant in Honduran unrelated NSCLP patients and unrelated unaffected controls and 2) to investigate the frequency of this variant in Colombian unrelated affected NSCLP patients and unrelated unaffected controls. STUDY DESIGN: Case-control studies. METHODS: Sanger sequencing of 99 unrelated Honduran NSCLP patients and 215 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. Sanger sequencing of 230 unrelated Colombian NSCLP patients and 146 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. RESULTS: In the Honduran population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 4.0 (P = .03), with a carrier frequency of seven of 99 (7.1%) in unrelated affected and four of 215 (1.9%) in unrelated unaffected individuals. In the Colombian population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 2.6 (P = .04), with a carrier frequency of 23 of 230 (10.0%) in unrelated affected and six of 146 (4.1%) in unrelated unaffected individuals. CONCLUSIONS: These findings support the role of ACSS2 in NSCLP in two independent Hispanic populations from Honduras and Colombia. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E336-E339, 2017.
Assuntos
Acetato-CoA Ligase/genética , Encéfalo/anormalidades , Fenda Labial/genética , Fissura Palatina/genética , Acetato-CoA Ligase/sangue , Estudos de Casos e Controles , Pré-Escolar , Fenda Labial/sangue , Fissura Palatina/sangue , Colômbia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Honduras , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodosRESUMO
OBJECTIVES/HYPOTHESIS: Orofacial clefts are the most common craniofacial birth defects in humans, with the majority of orofacial clefts occurring as nonsyndromic cleft lip with or without cleft palate (NSCLP). We previously demonstrated associations between single-nucleotide polymorphisms (SNPs) in the IRF6 gene and NSCLP in the Honduran population. Here we investigated other candidate genes and chromosomal regions associated with NSCLP identified from genome-wide association studies (GWAS), including MAFB, ABCA4, 8q24, 9q22, 10q25, and 17q22 in two independent Hispanic populations. STUDY DESIGN: Case-control and family-based association testing. METHODS: Honduran families with two or more members with NSCLP (multiplex) were identified. DNA was collected from affected and unaffected family members (488) and 99 gender-matched controls. NSCLP Colombian families were identified; DNA was collected from 26 proband-parent trios. All participants were genotyped for 17 SNPs in six chromosomal regions. Case-control association and family-based association testing (FBAT) analyses were conducted. RESULTS: Seven SNPs demonstrated association in at least one model in the Honduran population. In the Colombian families, five SNPs demonstrated significance in FBAT when patients with isolated cleft palate (CP) were included; four overlapped with SNPs demonstrating significance in the Honduran population, two with the same allele. One SNP retained significance with CP excluded. CONCLUSIONS: This study supports the previous GWAS findings and is the first to suggest a role for FOXE1, ABCA4, and MAFB in orofacial clefting in two separate Hispanic populations.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Fenda Labial/genética , Fissura Palatina/genética , Fatores de Transcrição Forkhead/genética , Predisposição Genética para Doença/epidemiologia , Fator de Transcrição MafB/genética , Polimorfismo de Nucleotídeo Único , Alelos , Estudos de Casos e Controles , Fenda Labial/etnologia , Fenda Labial/cirurgia , Fissura Palatina/etnologia , Fissura Palatina/cirurgia , Colômbia/etnologia , Intervalos de Confiança , Feminino , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Genótipo , Hispânico ou Latino/genética , Honduras/etnologia , Humanos , Incidência , Fatores Reguladores de Interferon/genética , Masculino , Razão de Chances , Linhagem , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES/HYPOTHESIS: Cleft lip with or without cleft palate (CL/P) is a common birth defect throughout the world. Linkage studies have shown interferon regulatory factor 6 (IRF6) to be associated with CL/P in multiple populations, including one in Honduras. It is unknown, however, whether rare sporadic mutations or common variants are the cause of this association, and reports exist supporting both hypotheses. Thus, it is important to determine the cause for this association in a Honduran population. STUDY DESIGN: Case-control and family-based association studies. METHODS: Families with two or more members affected by CL/P were identified. We collected DNA from affected and unaffected family members (608 total), and from 100 gender-matched controls from Honduras. We sequenced the exons of IRF6 for mutations in probands and controls. All patients were genotyped for single nucleotide polymorphisms (SNPs) rs642961 and rs2235371, which are proposed to have potential biological significance to IRF6 expression and function. RESULTS: We found no mutations in IRF6 in our CL/P probands. We found a risk association with the G allele of rs2235371 in both case-control (P = .01) and family-based association (P = .01) studies. We found no association with either allele of rs642961. CONCLUSIONS: This study suggests that common variants, rather than rare mutations, are the cause for association between IRF6 and nonsyndromic CL/P. rs2235371, but not rs642961, shows association with CL/P, suggesting a functional role for this polymorphism in our Honduran population. rs642961 has been previously reported to have an effect in other populations, suggesting that different populations may be affected by different polymorphisms.
Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Variação Genética , Fatores Reguladores de Interferon/genética , Polimorfismo de Nucleotídeo Único , Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Éxons/genética , Feminino , Genética Populacional , Honduras/epidemiologia , Humanos , Masculino , Análise de Sequência de DNARESUMO
Van der Woude syndrome (VWS) is an autosomal dominant inherited disease characterized by lower lip pits, cleft lip and/or cleft palate. Missense, nonsense and frameshift mutations in IRF6 have been revealed to be responsible for VWS in European, Asian, North American and Brazilian populations. However, the mutations responsible for VWS have not been studied in Central American populations. Here, we investigated the role of IRF6 in patients with VWS in a previously unstudied Honduran population. IRF6 mutations were identified in four out of five VWS families examined, which strongly suggests that mutations in IRF6 are responsible for VWS in this population. We reported three novel mutations and one previously described mutation. In the first family, a mother and daughter both exhibited a p.N88I mutation in the DNA-binding region of IRF6 that was not present in unaffected family members. In the second, we found a unique p.K101QfsX15 mutation in the affected patient, leading to a frameshift and early stop codon. In the third, we identified a p.Q208X mutation occurring in exon 6. In the fourth, we found a nonsense mutation in exon 9 (p.R412X), previously described in Brazilian and Northern European populations. In the fifth, we did not identify any unique exonic missense, nonsense or frameshift mutations. This study reports the first cases of IRF6 mutations in VWS patients in a Central American population, further confirming that the causal link between IRF6 and VWS is consistent across multiple populations.
Assuntos
Fatores Reguladores de Interferon/genética , Mutação/genética , Anormalidades Múltiplas/genética , Sequência de Bases , Estudos de Casos e Controles , Fenda Labial/genética , Fissura Palatina/genética , Cistos/genética , Éxons/genética , Família , Feminino , Honduras , Humanos , Lábio/anormalidades , Masculino , Dados de Sequência Molecular , LinhagemRESUMO
OBJECTIVES/HYPOTHESIS: Interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome (VWS), is a candidate gene for nonsyndromic cleft lip with or without cleft palate (NSCLP) because a number of studies have supported an association between NSCLP and single nucleotide polymorphisms (SNPs) in IRF6 in several populations. This project investigated the contribution of IRF6 to NSCLP in the Honduran population, a previously unstudied group with a high prevalence of NSCLP. STUDY DESIGN: Family-based joint linkage and association study. METHODS: A set of five SNPs in and around IRF6 previously reported to be associated with NSCLP were tested for association with NSCLP in 276 affected and unaffected Honduran individuals from 59 families with at least two members affected by clefting and at least one member with confirmed NSCLP. RESULTS: We observed support of linkage for three SNPs-rs1856161, rs2235371, and rs2235377-under a dominant model (log of odds [LODs] = 1.97, 1.56, 1.73, respectively). Subsequent single-point, haplotype, and joint linkage and association analyses continued to support the association with NSCLP (P < or = .05) at these three SNPs. When analysis was restricted to NSCLP cases, excluding cleft palate only cases, support for association strengthened. CONCLUSIONS: This is the first study to demonstrate that three candidate SNPs within IRF6 are significantly associated with NSCLP in the Honduran population, providing the first genetic clue to NSCLP observed in the Honduran population and confirming findings from populations in other parts of the world. Further studies are needed to identify the putative variant(s).