Hai Xuan Tang, Y‐Thanh Lu, Thi Minh Thi Ha, Nhat‐Thang Tran, Doan Minh Dang, Son Xuan Ly, Thu Ha Thi Bui, Son Ta Vo, Minh Doan Thai, Vu Dinh Nguyen, Thong Van Nguyen, Linh Thuy Dinh, Lan‐Anh Thi Luong, Kim‐Phuong Doan, Kim Huong Thi Nguyen, Thanh‐Thuy Thi Do, Dinh‐Kiet Truong, Hoa Giang, Hoai‐Nghia Nguyen, Thu Huong Nhut Trinh, Hung Sang Tang
{"title":"Parental mosaicism rather than de novo variants in FOXG1‐related syndrome and TUBA1A‐associated Tubulinopathy: Familial case reports","authors":"Hai Xuan Tang, Y‐Thanh Lu, Thi Minh Thi Ha, Nhat‐Thang Tran, Doan Minh Dang, Son Xuan Ly, Thu Ha Thi Bui, Son Ta Vo, Minh Doan Thai, Vu Dinh Nguyen, Thong Van Nguyen, Linh Thuy Dinh, Lan‐Anh Thi Luong, Kim‐Phuong Doan, Kim Huong Thi Nguyen, Thanh‐Thuy Thi Do, Dinh‐Kiet Truong, Hoa Giang, Hoai‐Nghia Nguyen, Thu Huong Nhut Trinh, Hung Sang Tang","doi":"10.1002/mgg3.2484","DOIUrl":null,"url":null,"abstract":"BackgroundDe novo variations are a primary cause of Rett syndrome and Tubulinopathy, accounting for over 90% of cases. Some studies have identified and documented parental inheritance by mosaicism in these two disorders, albeit with limited data.MethodsClinical characteristics and diagnosis, including genetic tests of members of two families, were obtained from medical reports.ResultsThe first family with Rett syndrome (RTT) presented with two offspring carrying <jats:italic>FOXG1</jats:italic> c.460dup. Both affected RTT pregnancies did not show anomalies within the first trimester, preventing prenatal recognition at an early stage. The second family had two of three offspring confirmed with <jats:italic>TUBA1A</jats:italic> c.172G>A related to Tubulinopathy. Both young couples from the two families harbored none of the variants correlating to their children's conditions. Diagnosis of parental mosaics with higher rates of recurrence was reasonably determined, and genetic counseling played a major role in guiding and managing their subsequent pregnancies.ConclusionIn genetic disorders with a high penetration of de novo variants, the risk of having a recurrent baby is an important topic to discuss with affected families. By examining variants that siblings share, clinical diagnosis can offer valuable information about the presence of mosaic inheritance. To effectively manage in the long term, adequate genetic counseling and strategic planning for future pregnancies should be emphasized to mitigate the risk of recurrent offspring.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"24 1","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Genetics & Genomic Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/mgg3.2484","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
BackgroundDe novo variations are a primary cause of Rett syndrome and Tubulinopathy, accounting for over 90% of cases. Some studies have identified and documented parental inheritance by mosaicism in these two disorders, albeit with limited data.MethodsClinical characteristics and diagnosis, including genetic tests of members of two families, were obtained from medical reports.ResultsThe first family with Rett syndrome (RTT) presented with two offspring carrying FOXG1 c.460dup. Both affected RTT pregnancies did not show anomalies within the first trimester, preventing prenatal recognition at an early stage. The second family had two of three offspring confirmed with TUBA1A c.172G>A related to Tubulinopathy. Both young couples from the two families harbored none of the variants correlating to their children's conditions. Diagnosis of parental mosaics with higher rates of recurrence was reasonably determined, and genetic counseling played a major role in guiding and managing their subsequent pregnancies.ConclusionIn genetic disorders with a high penetration of de novo variants, the risk of having a recurrent baby is an important topic to discuss with affected families. By examining variants that siblings share, clinical diagnosis can offer valuable information about the presence of mosaic inheritance. To effectively manage in the long term, adequate genetic counseling and strategic planning for future pregnancies should be emphasized to mitigate the risk of recurrent offspring.
期刊介绍:
Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care.
Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.