RESUMO
OBJECTIVE: Genetic carrier screening has the potential to identify couples at risk of having a child affected with an autosomal recessive or X-linked disorder. However, the current prevalence of carrier status for these conditions in developing countries is not well defined. This study assesses the prevalence of carrier status of selected genetic conditions utilizing an expanded, pan-ethnic genetic carrier screening panel (ECS) in a large population of Mexican patients. METHODS: Retrospective chart review of all patients tested with a single ECS panel at an international infertility center from 2012 to 2018 were included, and the prevalence of positive carrier status in a Mexican population was evaluated. RESULTS: Eight hundred five individuals were analyzed with ECS testing for 283 genetic conditions. Three hundred fifty-two carriers (43.7%) were identified with 503 pathogenic variants in 145 different genes. Seventeen of the 391 participating couples (4.34%) were identified as being at-risk couples. The most prevalent alleles found were associated with alpha thalassemia, cystic fibrosis, GJB2 nonsyndromic hearing loss, biotinidase deficiency, and familial Mediterranean fever. CONCLUSION: Based on the prevalence and severity of Mendelian disorders, we recommend that couples who wish to conceive regardless of their ethnicity background explore carrier screening and genetic counseling prior to reproductive medical treatment.
Assuntos
Triagem de Portadores Genéticos , Doenças Genéticas Inatas/epidemiologia , Cuidado Pré-Concepcional , Adulto , Biotinidase/genética , Deficiência de Biotinidase/epidemiologia , Deficiência de Biotinidase/genética , Conexina 26/genética , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Feminino , Aconselhamento Genético , Doenças Genéticas Inatas/genética , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/genética , Hemoglobina A/genética , Heterozigoto , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Pirina/genética , Estudos Retrospectivos , Medição de Risco , Talassemia alfa/epidemiologia , Talassemia alfa/genéticaAssuntos
Febre Familiar do Mediterrâneo/genética , Predisposição Genética para Doença/epidemiologia , Doenças Hereditárias Autoinflamatórias/genética , Pirina/genética , Febre Familiar do Mediterrâneo/epidemiologia , Feminino , França/epidemiologia , Variação Genética , Doenças Hereditárias Autoinflamatórias/epidemiologia , Hereditariedade/genética , Humanos , Masculino , Prevalência , Medição de RiscoRESUMO
We reviewed the medical records of patients with periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) to investigate the clinical course, treatment response, and association with MEFV gene mutation. Familial Mediterranean fever should be considered in patients with PFAPA who do not respond to adenotonsillectomy.
Assuntos
Adenoidectomia , Febre Familiar do Mediterrâneo/diagnóstico , Linfadenite/diagnóstico , Faringite/diagnóstico , Pirina/genética , Estomatite Aftosa/diagnóstico , Tonsilectomia , Criança , Pré-Escolar , Diagnóstico Diferencial , Doenças Endêmicas , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Feminino , Marcadores Genéticos , Heterozigoto , Humanos , Lactente , Linfadenite/complicações , Linfadenite/epidemiologia , Linfadenite/cirurgia , Masculino , Mutação , Faringite/complicações , Faringite/epidemiologia , Faringite/cirurgia , Estudos Retrospectivos , Estomatite Aftosa/complicações , Estomatite Aftosa/epidemiologia , Estomatite Aftosa/cirurgia , Síndrome , Resultado do Tratamento , Turquia/epidemiologiaRESUMO
BACKGROUND: Familial Mediterranean Fever and celiac disease are both related to auto-inflammation and/or auto-immunity and they share some common clinical features such as abdominal pain, diarrhea, bloating and flatulence. Objectives We aimed to determine the association of these two diseases, if present. METHODS: Totally 112 patients diagnosed with Familial Mediterranean Fever and 32 cases as healthy control were included in the study. All participants were examined for the evidence of celiac disease, with serum tissue transglutaminase IgA levels (tTG IgA). RESULTS: Totally 144 cases, 112 with Familial Mediterranean Fever and 32 healthy control cases were included in the study. tTG IgA positivity was determined in three cases with Familial Mediterranean Fever and in one case in control group. In that aspect there was no significant difference regarding the tTG IgA positivity between groups (P=0.81). Duodenum biopsy was performed to the tTG IgA positive cases and revealed Marsh Type 3b in two Familial Mediterranean Fever cases and Marsh Type 3c in the other one while the biopsy results were of the only tTG IgA positive case in control group was Marsh Type 3b. In HLA evaluation of the celiac cases; HLA DQ2 was present in two celiac cases of the Familial Mediterranean Fever group and in the only celiac case of the control group while HLA DQ8 was present in one celiac case of the Familial Mediterranean Fever group. CONCLUSIONS: We did not determine an association of Familial Mediterranean Fever with celiac disease. Larger studies with subgroup analysis are warranted to determine the relationship of these two diseases.
Assuntos
Doença Celíaca/complicações , Febre Familiar do Mediterrâneo/complicações , Autoanticorpos/sangue , Biópsia , Estudos de Casos e Controles , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Pré-Escolar , Estudos Transversais , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Feminino , Antígenos HLA-DQ/sangue , Humanos , Imunoglobulina A/sangue , Masculino , Prevalência , Transglutaminases/sangueRESUMO
Background Familial Mediterranean Fever and celiac disease are both related to auto-inflammation and/or auto-immunity and they share some common clinical features such as abdominal pain, diarrhea, bloating and flatulence. Objectives We aimed to determine the association of these two diseases, if present. Methods Totally 112 patients diagnosed with Familial Mediterranean Fever and 32 cases as healthy control were included in the study. All participants were examined for the evidence of celiac disease, with serum tissue transglutaminase IgA levels (tTG IgA). Results Totally 144 cases, 112 with Familial Mediterranean Fever and 32 healthy control cases were included in the study. tTG IgA positivity was determined in three cases with Familial Mediterranean Fever and in one case in control group. In that aspect there was no significant difference regarding the tTG IgA positivity between groups (P=0.81). Duodenum biopsy was performed to the tTG IgA positive cases and revealed Marsh Type 3b in two Familial Mediterranean Fever cases and Marsh Type 3c in the other one while the biopsy results were of the only tTG IgA positive case in control group was Marsh Type 3b. In HLA evaluation of the celiac cases; HLA DQ2 was present in two celiac cases of the Familial Mediterranean Fever group and in the only celiac case of the control group while HLA DQ8 was present in one celiac case of the Familial Mediterranean Fever group. Conclusions We did not determine an association of Familial Mediterranean Fever with celiac disease. Larger studies with subgroup analysis are warranted to determine the relationship of these two diseases. .
Contexto A Febre Familiar do Mediterrâneo e a doença celíaca são ambas relacionadas com auto-inflamação e/ou auto-imunidade e partilham algumas características clínicas comuns tais como dor abdominal, diarréia, distensão abdominal e flatulência. Objetivo Determinar a associação destas duas doenças, se presente. Métodos Um total de 112 pacientes diagnosticados com Febre Familiar do Mediterrâneo e 32 casos como controle saudável foram incluídos no estudo. Todos os participantes foram examinados para a evidência da doença celíaca, com níveis de IgA séricos transglutaminase (tTG IgA). Resultados Um total de 144 casos, 112 com Febre Familiar do Mediterrâneo e 32 casos controle saudável foram incluídos no estudo. A positividade tTG IgA foi determinada em três casos com Febre Familiar do Mediterrâneo e em um caso no grupo controle. Neste aspecto não há nenhuma diferença significativa em relação a positividade tTG IgA entre os grupos (P= 0,81). Biópsia de duodeno realizado para os casos positivos de tTG IgA e revelou Marsh tipo 3b em dois casos de Febre Familiar e Marsh tipo 3C no outro, enquanto o resultado da biópsia do único caso positivo tTG IgA no grupo controle foi Marsh tipo 3b. Na avaliação de HLA dos casos de doença celíaca, HLA DQ2 esteve presente em dois casos de doença celíacas do grupo Febre Familiar do Mediterrâneo e no caso celíaco do grupo controle, enquanto HLA-DQ8 estava presente em um caso de doença celíaca do grupo Febre Familiar do Mediterrâneo. Conclusão Não se determinou uma associação de Febre Familiar do Mediterrâneo com doença celíaca. Maiores estudos com análise de subgrupo são necessários para determinar a relação entre estas duas doenças. .
Assuntos
Pré-Escolar , Feminino , Humanos , Masculino , Doença Celíaca/complicações , Febre Familiar do Mediterrâneo/complicações , Autoanticorpos/sangue , Biópsia , Estudos de Casos e Controles , Estudos Transversais , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Antígenos HLA-DQ/sangue , Imunoglobulina A/sangue , Prevalência , Transglutaminases/sangueRESUMO
Hereditary periodic fever syndromes (HPFS) are rare genetic diseases characterized by recurrent episodes of inflammation. Little information is available concerning HPFS in Latin American Hispanic population. The purpose of this study was to determine the clinical and genetic features of HPFS in Chilean population. A multicenter retrospective study of Hispanic Chilean patients with genetically confirmed HPFS was performed. We included 13 patients, 8 with familial Mediterranean fever (FMF) and 5 with TNF receptor-associated periodic syndrome (TRAPS), evaluated at rheumatology or pediatric rheumatology clinics between January 2007 and December 2010. Median age of symptoms onset was 8 years (range 1-35) and 8 years (range 0.3-21) for FMF and TRAPS, respectively. Median duration of fever was 3 days (range 2.5-15) for FMF and 21 days (range 9.5-30) for TRAPS. Genotyping of the MEFV gene in FMF patients revealed a homozygous M694V missense mutation in one patient, and heterozygous missense mutations in seven patients: M694V (n = 3), E148Q, R717H, A744S, and A511V. Sequencing of the TNFRSF1A gene in TRAPS patients revealed heterozygous missense mutations in four patients: T50M, C30R, R92Q, and IVS3+30:GâA, and a two-base pair deletion (IVS2-17_18del2bpCT) in one patient. Mutation in MEFV R717H and mutations in TNFRSF1A IVS2-17_18del2bpCT and IVS3+30:GâA are novel and have not been described previously. This study reports the largest series of genetically confirmed HPFS in Latin America, and adds evidence regarding the clinical and genetic characteristics of patients with FMF and TRAPS in Hispanic population. Mutations identified in MEFV and TNFRSF1A genes include defects reported in other ethnicities and novel mutations.
Assuntos
Proteínas do Citoesqueleto/genética , Febre Familiar do Mediterrâneo , Predisposição Genética para Doença , Mutação de Sentido Incorreto , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Adolescente , Adulto , Criança , Pré-Escolar , Chile/epidemiologia , Análise Mutacional de DNA , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/patologia , Feminino , Humanos , Lactente , Masculino , Pirina , Recidiva , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To characterize the clinical and genetic features of familial Mediterranean fever (FMF). STUDY DESIGN: Clinical presentation and MEditerranean FeVer mutation type of all patients with FMF, who first manifested the disease at < or =2 years of age were analyzed and compared with patients who first presented with FMF between 2 and 16 years. RESULTS: Of 814 patients with FMF, in 254 patients (31.2%) the first FMF attack was at < or =2 years of age, with a mean age at onset of 1.1 +/- 0.8 years. They were compared with 242 patients who presented with their first manifestation of FMF at 2 to 16 years. The clinical manifestations of FMF were comparable in the 2 patient groups, but the delay of diagnosis was longer in patients with early presentation (3.2 +/- 3.2 years vs.1.9 +/- 2.7 years in the group with onset at 2-16 years, P < .001). A subgroup of patients (60/254), who were diagnosed at < or =2 years had the highest rate of attacks of fever alone as their sole manifestation (40.0% vs 8.4%, P < .05), and less peritonitis (45% vs 86.1%, P < .05) and pleuritis (3.4% vs 32.9%, P < .05). Most of these patients were homozygous for the M694V mutation and were of North African (Sephardic Jewish) extraction. CONCLUSION: In early life, FMF often begins with an atypical presentation, characterized by attacks of fever alone, and its diagnosis and initiation of treatment is therefore significantly delayed.
Assuntos
Febre Familiar do Mediterrâneo/diagnóstico , Adolescente , Idade de Início , Criança , Pré-Escolar , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Feminino , Humanos , Lactente , Masculino , Mutação , Fenótipo , PirinaRESUMO
Familial Mediterranean fever (MFF) is an autosomic recessive, inherited inflammatory disease principally seen in persons from the Mediterranean area. Clinical findings include fever, abdominal pain, and pleuritis. The most severe complication of MFF is renal amyloidosis, manifested as nephrotic syndrome, which evolves into chronic renal failure. In this study, we described clinical findings, evolution, and response to treatment in 52 patients diagnosed with MFF living in Mexico City in whom the most important clinical features were fever and abdominal pain. Differing from previous reported series of patients from the Mediterranean area, patient developed renal amyloidosis during the 20-year follow-up, which suggests that an environmental factor might have a significant influence in development of renal amyloidosis.
Assuntos
Febre Familiar do Mediterrâneo/epidemiologia , Dor Abdominal/etiologia , Dor Abdominal/cirurgia , Adolescente , Adulto , Idoso , Amiloidose Familiar/epidemiologia , Amiloidose Familiar/etnologia , Amiloidose Familiar/etiologia , Amiloidose Familiar/prevenção & controle , Criança , Pré-Escolar , Colchicina/uso terapêutico , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/etnologia , Feminino , Seguimentos , Humanos , Nefropatias/epidemiologia , Nefropatias/etnologia , Nefropatias/prevenção & controle , Laparotomia/estatística & dados numéricos , Masculino , Ciclo Menstrual , México/epidemiologia , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez , Síria/etnologia , Procedimentos DesnecessáriosRESUMO
OBJECTIVES: Based on the fact that Henoch-Schönlein purpura (HSP) occurs in approximately 5% of persons with familial Mediterranean fever (FMF), we assessed the prevalence and significance of FMF gene mutations in children with one or more episodes of HSP. STUDY DESIGN: Thirty-four boys and 18 girls treated for HSP at Rambam Medical Center were interviewed and asked to donate blood. Mean age at disease onset was 6.7+/-2. 4 years, and mean follow-up was 3.8+/-1.3 years. Six predominant mutations (M694V, M680I, M694I, V726A, K695R, E148Q) in the MEFV gene were studied. RESULTS: Nine heterozygotes, three homozygotes and two compound heterozygotes, were identified. Altogether, five persons (10%) carried two mutated MEFV alleles, a number significantly exceeding that determined for the general Israeli population (1%-2%). Of these, three displayed genotypes associated with a mild form of disease (M694V/E148Q and V726A/V726A), and two had genotypes normally observed in disease-free persons (E148Q/K695R and E148Q/E148Q). CONCLUSIONS: Occult FMF cases much more numerous than expected were identified among children presenting with HSP. Such children should be closely monitored for renal complications, and treatment with colchicine should be considered.
Assuntos
Febre Familiar do Mediterrâneo/genética , Vasculite por IgA/genética , Mutação Puntual/genética , Proteínas/genética , Adolescente , Idade de Início , Alelos , Criança , Pré-Escolar , Proteínas do Citoesqueleto , Análise Mutacional de DNA , Febre Familiar do Mediterrâneo/epidemiologia , Feminino , Genótipo , Humanos , Vasculite por IgA/epidemiologia , Masculino , Prevalência , PirinaRESUMO
We describe four members in a family of 8 individuals over 3 generations with the autosomal dominant inherited periodic fever syndrome tumor necrosis factor receptor-associated periodic syndrome (TRAPS). The patients had recurrent episodes of fever, abdominal pain, arthritis, and rash. We examined the gene coding for the tumor necrosis factor receptor TNFRSF1A in all first-degree family members. In all 4 symptomatic members of the family, a hitherto undescribed mutation C98Y (380G-->A) in the TNFRSF1A gene was identified. In contrast, this mutation was not found in the 4 family members reported to be healthy nor in 50 normal control patients. The youngest member of the family, a 2-year-old boy, was treated successfully with etanercept.
Assuntos
Antígenos CD/genética , Febre Familiar do Mediterrâneo/genética , Genes Dominantes/genética , Mutação/genética , Receptores do Fator de Necrose Tumoral/genética , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos de Casos e Controles , Criança , Análise Mutacional de DNA , Dinamarca/epidemiologia , Etanercepte , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/epidemiologia , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lactente , Masculino , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Receptores do Fator de Necrose Tumoral/uso terapêutico , Receptores Tipo I de Fatores de Necrose Tumoral , Mapeamento por RestriçãoRESUMO
Of 59 Sephardic Jewish and Arab children in whom functional abdominal pain was diagnosed, we found that 20% were homozygote for the familial Mediterranean fever gene. Inclusion of genetic screening for familial Mediterranean fever may be advisable in the investigation of recurrent abdominal pain among children of Mediterranean extraction.
Assuntos
Febre Familiar do Mediterrâneo/genética , Dor Abdominal/genética , Dor Abdominal/patologia , Adolescente , Criança , Pré-Escolar , Febre Familiar do Mediterrâneo/epidemiologia , Feminino , Testes Genéticos/métodos , Humanos , Incidência , Masculino , Recidiva , Fatores de RiscoRESUMO
Con el fin de difundir la existencia de pacientes con fiebre mediterránea familiar en la ciudad de México, se informan 47 casos en 9 familias, cuyas manifestaciones principales fueron: dolor abdominal en 46, fiebre en 45, dolor pleural en 10 y dolor articular en 8. Todas estas manifestaciones se presentaron en forma recurrente. Ninguno de los pacientes hasta la fecha tiene amiloidosis