genetic Archives - Revista Brasileira de Ginecologia e Obstetrícia
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Revista Brasileira de Ginecologia e Obstetrícia. 2024;46:e-rbgo12
, , , , , , , , Endometriosis is a complex disease that affects 10-15% of women of reproductive age. Familial studies show that relatives of affected patients have a higher risk of developing the disease, implicating a genetic role for this disorder. Little is known about the impact of germline genomic copy number variant (CNV) polymorphisms on the heredity of the disease. In this study, we describe a rare CNV identified in two sisters with familial endometriosis, which contain genes that may increase the susceptibility and progression of this disease. We investigated the presence of CNVs from the endometrium and blood of the sisters with endometriosis and normal endometrium of five women as controls without the disease using array-CGH through the Agilent 2x400K platform. We excluded common CNVs that were present in the database of genomic variation. We identified, in both sisters, a rare CNV gain affecting 113kb at band 3q12.2 involving two candidate genes: ADGRG7 and TFG. The CNV gain was validated by qPCR. ADGRG7 is located at 3q12.2 and encodes a G protein-coupled receptor influencing the NF-kappaβ pathway. TFG participates in chromosomal translocations associated with hematologic tumor and soft tissue sarcomas, and is also involved in the NF-kappa B pathway. The CNV gain in this family provides a new candidate genetic marker for future familial endometriosis studies. Additional longitudinal studies of affected families must confirm any associations between this rare CNV gain and genes involved in the NF-kappaβ pathway in predisposition to endometriosis.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2024;46:e-rbgo12
, , , , , , , , Endometriosis is a complex disease that affects 10-15% of women of reproductive age. Familial studies show that relatives of affected patients have a higher risk of developing the disease, implicating a genetic role for this disorder. Little is known about the impact of germline genomic copy number variant (CNV) polymorphisms on the heredity of the disease. In this study, we describe a rare CNV identified in two sisters with familial endometriosis, which contain genes that may increase the susceptibility and progression of this disease. We investigated the presence of CNVs from the endometrium and blood of the sisters with endometriosis and normal endometrium of five women as controls without the disease using array-CGH through the Agilent 2x400K platform. We excluded common CNVs that were present in the database of genomic variation. We identified, in both sisters, a rare CNV gain affecting 113kb at band 3q12.2 involving two candidate genes: ADGRG7 and TFG. The CNV gain was validated by qPCR. ADGRG7 is located at 3q12.2 and encodes a G protein-coupled receptor influencing the NF-kappaβ pathway. TFG participates in chromosomal translocations associated with hematologic tumor and soft tissue sarcomas, and is also involved in the NF-kappa B pathway. The CNV gain in this family provides a new candidate genetic marker for future familial endometriosis studies. Additional longitudinal studies of affected families must confirm any associations between this rare CNV gain and genes involved in the NF-kappaβ pathway in predisposition to endometriosis.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2014;36(3):113-117
DOI 10.1590/S0100-72032014000300004
To investigate the prevalence of chromosomal abnormalities in couples with two or more recurrent first trimester miscarriages of unknown cause.
The study was conducted on 151 women and 94 partners who had an obstetrical history of two or more consecutive first trimester abortions (1-12 weeks of gestation). The controls were 100 healthy women without a history of pregnancy loss. Chromosomal analysis was performed on peripheral blood lymphocytes cultured for 72 hours, using Trypsin-Giemsa (GTG) banding. In all cases, at least 30 metaphases were analyzed and 2 karyotypes were prepared, using light microscopy. The statistical analysis was performed using the Student t-test for normally distributed data and the Mann-Whitney test for non-parametric data. The Kruskal-Wallis test or Analysis of Variance was used to compare the mean values between three or more groups. The software used was Statistical Package for the Social Sciences (SPSS), version 17.0.
The frequency of chromosomal abnormalities in women with recurrent miscarriages was 7.3%, including 4.7% with X-chromosome mosaicism, 2% with reciprocal translocations and 0.6% with Robertsonian translocations. A total of 2.1% of the partners of women with recurrent miscarriages had chromosomal abnormalities, including 1% with X-chromosome mosaicism and 1% with inversions. Among the controls, 1% had mosaicism.
An association between chromosomal abnormalities and recurrent miscarriage in the first trimester of pregnancy (OR=7.7; 95%CI 1.2--170.5) was observed in the present study. Etiologic identification of genetic factors represents important clinical information for genetic counseling and orientation of the couple about the risk for future pregnancies and decreases the number of investigations needed to elucidate the possible causes of miscarriages.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2014;36(3):113-117
DOI 10.1590/S0100-72032014000300004
To investigate the prevalence of chromosomal abnormalities in couples with two or more recurrent first trimester miscarriages of unknown cause.
The study was conducted on 151 women and 94 partners who had an obstetrical history of two or more consecutive first trimester abortions (1-12 weeks of gestation). The controls were 100 healthy women without a history of pregnancy loss. Chromosomal analysis was performed on peripheral blood lymphocytes cultured for 72 hours, using Trypsin-Giemsa (GTG) banding. In all cases, at least 30 metaphases were analyzed and 2 karyotypes were prepared, using light microscopy. The statistical analysis was performed using the Student t-test for normally distributed data and the Mann-Whitney test for non-parametric data. The Kruskal-Wallis test or Analysis of Variance was used to compare the mean values between three or more groups. The software used was Statistical Package for the Social Sciences (SPSS), version 17.0.
The frequency of chromosomal abnormalities in women with recurrent miscarriages was 7.3%, including 4.7% with X-chromosome mosaicism, 2% with reciprocal translocations and 0.6% with Robertsonian translocations. A total of 2.1% of the partners of women with recurrent miscarriages had chromosomal abnormalities, including 1% with X-chromosome mosaicism and 1% with inversions. Among the controls, 1% had mosaicism.
An association between chromosomal abnormalities and recurrent miscarriage in the first trimester of pregnancy (OR=7.7; 95%CI 1.2--170.5) was observed in the present study. Etiologic identification of genetic factors represents important clinical information for genetic counseling and orientation of the couple about the risk for future pregnancies and decreases the number of investigations needed to elucidate the possible causes of miscarriages.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2011;33(5):246-251
DOI 10.1590/S0100-72032011000500007
PURPOSE: to evaluate the prevalence of cytogenetic alterations and chromosomic polymorphism in couples with a subfertility phenotype in a Brazilian population. METHODS: karyotype analysis through G and C banding of 1,236 individuals who presented the subfertility phenotype, from two different centers (public and private) were included in the study. These patients were classified in two sub-groups: one with two or more gestational consecutive losses or not and the o with, at least, one gestacional loss or absence of conception. Karyotype results were evaluated in different groups and frequencies were calculated. Statistical analyses were carried out through Fisher's exact test and Odds Ratio analysis. RESULTS: approximately 25% of the cases presented abnormal karyotype results, including numerical and structural alterations and also polymorphic variants. In both centers, the prevalence of polymorphic variants was 8.9 and 3.8%, respectively. CONCLUSIONS: there was no significant difference between the prevalence of polymorphic variants and other abnormalities in individuals with or without previous history of reproductive loss. The results of the present study reinforce the need of adequate disclosure of complete cytogenetic information in the karyotype results, with specific attention in relation to the polymorphic variants.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2011;33(5):246-251
DOI 10.1590/S0100-72032011000500007
PURPOSE: to evaluate the prevalence of cytogenetic alterations and chromosomic polymorphism in couples with a subfertility phenotype in a Brazilian population. METHODS: karyotype analysis through G and C banding of 1,236 individuals who presented the subfertility phenotype, from two different centers (public and private) were included in the study. These patients were classified in two sub-groups: one with two or more gestational consecutive losses or not and the o with, at least, one gestacional loss or absence of conception. Karyotype results were evaluated in different groups and frequencies were calculated. Statistical analyses were carried out through Fisher's exact test and Odds Ratio analysis. RESULTS: approximately 25% of the cases presented abnormal karyotype results, including numerical and structural alterations and also polymorphic variants. In both centers, the prevalence of polymorphic variants was 8.9 and 3.8%, respectively. CONCLUSIONS: there was no significant difference between the prevalence of polymorphic variants and other abnormalities in individuals with or without previous history of reproductive loss. The results of the present study reinforce the need of adequate disclosure of complete cytogenetic information in the karyotype results, with specific attention in relation to the polymorphic variants.