Análise de segregação complexa de 1.792 famílias com fenda lábio-palatina na América do Sul: 1967-1997

Although several studies have demonstrated familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL/P), its model of inheritance remains uncertain. We report the results of complex segregation analysis performed in South American families with a newborn affected with CL/P. Families of 1,792 consecutive newborns affected with CL/P and registered during the period 1967 to 1997 were studied. A model that did not include a major locus was the best-fitting model for CL/P families. This result is in agreement with previous studies which showed a significant association of several putative susceptibility loci and CL/P, indicating that the genes involved in CL/P are likely to have only a very modest impact on disease risk.Os estudos sobre fendas lábio-palatinas (FL/P) demonstram existir uma maior incidência do defeito nas famílias de afetados, mas seu modo de herança permanece indefinido. Esse trabalho apresenta os resultados de uma análise de segregação complexa realizada em 1.792 famílias sul-americanas que possuíam um recém-nascido com FL/P. Essas crianças foram registradas entre 1967 e 1997 e os nascimentos foram consecutivos. Um modelo sem um locus principal foi o que melhor se adequou às famílias de FL/P estudadas. Esse resultado está de acordo com estudos anteriores que mostraram uma significativa associação entre vários loci de suscetibilidade e FL/P, indicando que os genes relacionados com FL/P, isoladamente, contribuem pouco para o risco desse defeito

Complex segregation analysis of 1,792 cleft lip and palate families in South America: 1967-1997

Os estudos sobre fendas lábio-palatinas (FL/P) demonstram existir uma maior incidência do defeito nas famílias de afetados, mas seu modo de herança permanece indefinido. Esse trabalho apresenta os resultados de uma análise de segregação complexa realizada em 1.792 famílias sul-americanas que possuíam um recém-nascido com FL/P. Essas crianças foram registradas entre 1967 e 1997 e os nascimentos foram consecutivos. Um modelo sem um locus principal foi o que melhor se adequou às famílias de FL/P estudadas. Esse resultado está de acordo com estudos anteriores que mostraram uma significativa associação entre vários loci de suscetibilidade e FL/P, indicando que os genes relacionados com FL/P, isoladamente, contribuem pouco para o risco desse defeito.Although several studies have demonstrated familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL/P), its model of inheritance remains uncertain. We report the results of complex segregation analysis performed in South American families with a newborn affected with CL/P. Families of 1,792 consecutive newborns affected with CL/P and registered during the period 1967 to 1997 were studied. A model that did not include a major locus was the best-fitting model for CL/P families. This result is in agreement with previous studies which showed a significant association of several putative susceptibility loci and CL/P, indicating that the genes involved in CL/P are likely to have only a very modest impact on disease risk

Molecular analysis of holoprosencephaly in South America

Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases.250262Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

A large, ten-generation family with autosomal dominant preaxial polydactyly/triphalangeal thumb: Historical, clinical, genealogical, and molecular studies

We present a large, ten-generation family of 273 individuals with 84 people having preaxial polydactyly/triphalangeal thumb due to a pathogenic variant in the zone of polarizing activity regulatory sequence (ZRS) within the exon 5 of LMBR1. The causative change maps to position 396 of the ZRS, located at position c.423 + 4909C > T (chr7:156791480; hg38; LMBR1 ENST00000353442.10; rs606231153 NG_009240.2) in the intron 5 of LMBR1. The first affected individual with the disorder was traced back to mid-1700, when some settlers and workers established in Cervera de Buitrago, a small village about 82 km North to Madrid. Clinical and radiological studies of most of the affected members have been performed for 42 years (follow-up of the family by LFGA). Molecular studies have confirmed a pathogenic variant in the ZRS that segregates in this family. To the best of our knowledge, this is the largest family with preaxial polydactyly/triphalangeal thumb reported so far.Instituto de Salud Carlos III, Grant/Award Number: PI20/0105

Sentinel phenotype for rubella embryopathy: time-space distribution in Brazil

The dyad comprising eye anomalies and congenital heart defects in the same newborn has been proposed as the best sentinel phenotype for the early detection of rubella embryopathy. Time-space birth prevalence distributions of the eye-heart dyad were described in 36 Brazilian hospitals from the Latin-American Collaborative Study of Congenital Anomalies - ECLAMC network, for the period 1994-2008. Seventy dyad cases observed among 554,531 births showed seasonal variation (Χ2 = 5.84; p < 0.05), suggesting an environmental etiology, with an increase in cases in October-March and acrophase in December. The secular distribution of dyad prevalence rates was consistent with the distribution of rubella cases in Brazil, showing a decrease from 1994 to 2004, followed by an increase until 2008. Two geographic clusters were identified, one with high and the other with low dyad prevalence. In the high prevalence cluster, a secular increase was observed, starting in 1999, matching the rubella epidemic waves observed in Brazil in 1998-2000 and 2006

Molecular analysis of holoprosencephaly in South America

Submitted by Santos Bárbara ([email protected]) on 2015-03-03T13:20:16Z No. of bitstreams: 1 Molecular analysis of holoprosencephaly in South America.pdf: 1134600 bytes, checksum: ca8b31fc87aa2e99d5a446f2722eba78 (MD5)Approved for entry into archive by Santos Bárbara ([email protected]) on 2015-03-03T13:20:29Z (GMT) No. of bitstreams: 1 Molecular analysis of holoprosencephaly in South America.pdf: 1134600 bytes, checksum: ca8b31fc87aa2e99d5a446f2722eba78 (MD5)Approved for entry into archive by Santos Bárbara ([email protected]) on 2015-03-03T14:00:31Z (GMT) No. of bitstreams: 1 Molecular analysis of holoprosencephaly in South America.pdf: 1134600 bytes, checksum: ca8b31fc87aa2e99d5a446f2722eba78 (MD5)Made available in DSpace on 2015-03-03T14:00:31Z (GMT). No. of bitstreams: 1 Molecular analysis of holoprosencephaly in South America.pdf: 1134600 bytes, checksum: ca8b31fc87aa2e99d5a446f2722eba78 (MD5) Previous issue date: 2014Universidade Federal do Rio de Janeiro. Departamento de Genética. Estudo Colaborativo Latino Americano de Malformações Congênitas. Rio de Janeiro, RJ, Brasil. / Instituto Nacional de Genética Médica Populacional, Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcantara Gomes. Departamento de Genética. Rio de Janeiro, RJ, Brasil.Instituto Cândida Vargas. Maternidade Cândida Vargas. João Pessoa, PB, Brasil.Centro di Consulenza Genetica e di Teratologia della Riproduzione. Dipartimento Materno Infantile. ARNAS Garibaldi Nesima. Catania, CT, Italy.Universidade Estadual de Campinas. Departamento de Genética Médica. Campinas, SP, Brasil.Hospital das Clínicas de Porto Alegre. Serviço de Genética Médica. Porto Alegre, RS, Brasil.Registro Campano Difetti Congeniti. Azienda Ospedaliera “Gaetano Rummo”. Benevento, BN, Italy.Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Centro de Genética Médica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil. / Fundação Oswaldo Cruz. Estudo Colaborativo Latino Americano de Malformações Congênitas. Laboratório de Epidemiologia de Defeitos Congênitos. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Câncer. Programa de Genética. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Câncer. Programa de Genética. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Genética Médica Populacional, Rio de Janeiro, RJ, Brasil. / Centro de Educación Médica e Investigación Clínica. Estudio Colaborativo Latino Americano de Malformaciones Congenitas. Buenos Aires, Argentina.Universidade Federal do Rio de Janeiro. Departamento de Genética. Estudo Colaborativo Latino Americano de Malformações Congênitas. Rio de Janeiro, RJ, Brasil. / Instituto Nacional de Genética Médica Populacional, Rio de Janeiro, RJ, Brasil.Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collabo-rative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lat-eral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female pa-tients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplifica-tion (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genesSHH,ZIC2,SIX3andTGIFwere performed in 119 patients, revealing eight mutations inSHH,two mutations inSIX3and two mutations inZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correla-tions and contribute to the development of additional strategies for the analysis of new cases

Sentinel phenotype for rubella embryopathy: time-space distribution in Brazil

The dyad comprising eye anomalies and congenital heart defects in the same newborn has been proposed as the best sentinel phenotype for the early detection of rubella embryopathy. Time-space birth prevalence distributions of the eye-heart dyad were described in 36 Brazilian hospitals from the Latin-American Collaborative Study of Congenital Anomalies - ECLAMC network, for the period 1994-2008. Seventy dyad cases observed among 554,531 births showed seasonal variation (Χ2 = 5.84; p < 0.05), suggesting an environmental etiology, with an increase in cases in October-March and acrophase in December. The secular distribution of dyad prevalence rates was consistent with the distribution of rubella cases in Brazil, showing a decrease from 1994 to 2004, followed by an increase until 2008. Two geographic clusters were identified, one with high and the other with low dyad prevalence. In the high prevalence cluster, a secular increase was observed, starting in 1999, matching the rubella epidemic waves observed in Brazil in 1998-2000 and 2006

The Latin American network for congenital malformation surveillance : ReLAMC

Q1Q1The early detection of congenital anomaly epidemics occurs when comparing current with previous frequencies in the same population. The success of epidemiologic surveillance depends on numerous factors, including the accuracy of the rates available in the base period, wide population coverage, and short periodicity of analysis. This study aims to describe the Latin American network of congenital malformation surveillance: ReLAMC, created to increase epidemiologic surveillance in Latin America. We describe the main steps, tasks, strategies used, and preliminary results. From 2017 to 2019, five national registries (Argentina [RENAC], Brazil [SINASC/SIM-BRS], Chile [RENACH], Costa Rica [CREC], Paraguay [RENADECOPY-PNPDC]), six regional registries (Bogotá [PVSDC- Bogota], Cali [PVSDC-Cali], Maule [RRMC SSM], Nicaragua [SVDC], Nuevo-León [ReDeCon HU], S~ao Paulo [SINASC/SIM-MSP]) and the ECLAMC hospital network sent data to ReLAMC on a total population of 9,152,674 births, with a total of 101,749 malformed newborns (1.1%; 95% CI 1.10–1.12). Of the 9,000,651 births in countries covering both live and stillbirths, 88,881 were stillborn (0.99%; 95% CI 0.98–0.99), and among stillborns, 6,755 were malformed (7.61%; 95% CI 7.44–7.79). The microcephaly rate was 2.45 per 10,000 births (95% CI 2.35–2.55), hydrocephaly 3.03 (2.92–3.14), spina bifida 2.89 (2.78–3.00), congenital heart defects 15.53 (15.27–15.79), cleft lip 2.02 (1.93–2.11), cleft palate and lip 2.77 (2.66–2.88), talipes 2.56 (2.46–2.67), conjoined twins 0.16 (0.14–0.19), and Down syndrome 5.33 (5.18–5.48). Each congenital anomaly showed heterogeneity in prevalence rates among registries. The harmonization of data in relation to operational differences between registries is the next step in developing the common ReLAMC database.Revista Internacional - Indexad