Delineation of the Genetic Architecture and Clinical Polymorphism of 3q29 Duplication Syndrome: A Review of the Literature and a Report of Two Novel Patients With Single‐Gene BDH1 Duplications
ABSTRACT Background Chromosome 3q29 duplication syndrome is a rare chromosomal disorder with a frequency of 1:5000 in patients with a neurodevelopmental phenotype. The syndrome is characterized by phenotypic polymorphism and reduced penetrance. Methods Patients were investigated by performing a cyto...
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2025-01-01
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| author | A. A. Kashevarova M. E. Lopatkina O. Yu. Vasilyeva D. A. Fedotov A. D. Lobanov E. A. Fonova I. Z. Zhalsanova A. A. Zarubin O. A. Salyukova E. O. Belyaeva V. V. Petrova E. G. Ravzhaeva A. A. Agafonova A. D. Cheremnykh N. B. Torkhova S. L. Vovk I. N. Lebedev |
| author_facet | A. A. Kashevarova M. E. Lopatkina O. Yu. Vasilyeva D. A. Fedotov A. D. Lobanov E. A. Fonova I. Z. Zhalsanova A. A. Zarubin O. A. Salyukova E. O. Belyaeva V. V. Petrova E. G. Ravzhaeva A. A. Agafonova A. D. Cheremnykh N. B. Torkhova S. L. Vovk I. N. Lebedev |
| author_sort | A. A. Kashevarova |
| collection | DOAJ |
| description | ABSTRACT Background Chromosome 3q29 duplication syndrome is a rare chromosomal disorder with a frequency of 1:5000 in patients with a neurodevelopmental phenotype. The syndrome is characterized by phenotypic polymorphism and reduced penetrance. Methods Patients were investigated by performing a cytogenetic analysis of GTG‐banded metaphases, aCGH with the SurePrint G3 Human CGH Microarray 8×60K, qPCR, FISH, and WES. Results Here, we report five new patients with atypical duplications overlapping with the 3q29 duplication syndrome region and no other genetic findings. In two patients, duplications were found in the single BDH1 gene, a candidate gene for the 3q29 duplication phenotype. For the first time, we delineated and described the smallest minimal critical region, including the single BDH1 gene; in our patients, this region was associated with ASD, heart defects, biliary tract dysfunction, and obesity. The frequencies of the pathological phenotypes in duplication carriers reported in the literature were calculated and compared with those in patients with 3q29 deletions. Most of the phenotypes were observed in both groups but were significantly less common among individuals with 3q29 duplications. Mirrored phenotypes in patients with duplications and deletions included overweight and weight deficit. Schizophrenia, generalized anxiety disorder, and recurrent ear infections were unique phenotypes of patients carrying deletions. Conclusion Chromosome 3q29 duplication syndrome is characterized by a complex genetic architecture and clinical polymorphism. |
| format | Article |
| id | doaj-art-a90605a6594345c3880ab0e979d9307d |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj-art-a90605a6594345c3880ab0e979d9307d2025-01-24T08:16:42ZengWileyMolecular Genetics & Genomic Medicine2324-92692025-01-01131n/an/a10.1002/mgg3.70047Delineation of the Genetic Architecture and Clinical Polymorphism of 3q29 Duplication Syndrome: A Review of the Literature and a Report of Two Novel Patients With Single‐Gene BDH1 DuplicationsA. A. Kashevarova0M. E. Lopatkina1O. Yu. Vasilyeva2D. A. Fedotov3A. D. Lobanov4E. A. Fonova5I. Z. Zhalsanova6A. A. Zarubin7O. A. Salyukova8E. O. Belyaeva9V. V. Petrova10E. G. Ravzhaeva11A. A. Agafonova12A. D. Cheremnykh13N. B. Torkhova14S. L. Vovk15I. N. Lebedev16Laboratory of Cytogenetics, Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaLaboratory of Ontogenetics, Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaLaboratory of Cytogenetics, Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaLaboratory of Ontogenetics, Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaLaboratory of Ontogenetics, Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaLaboratory of Ontogenetics, Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaLaboratory of Genomics of Orphan Diseases, Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaLaboratory of Population Genetics, Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaLaboratory of Ontogenetics, Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaLaboratory of Ontogenetics, Research Institute of Medical Genetics Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk RussiaABSTRACT Background Chromosome 3q29 duplication syndrome is a rare chromosomal disorder with a frequency of 1:5000 in patients with a neurodevelopmental phenotype. The syndrome is characterized by phenotypic polymorphism and reduced penetrance. Methods Patients were investigated by performing a cytogenetic analysis of GTG‐banded metaphases, aCGH with the SurePrint G3 Human CGH Microarray 8×60K, qPCR, FISH, and WES. Results Here, we report five new patients with atypical duplications overlapping with the 3q29 duplication syndrome region and no other genetic findings. In two patients, duplications were found in the single BDH1 gene, a candidate gene for the 3q29 duplication phenotype. For the first time, we delineated and described the smallest minimal critical region, including the single BDH1 gene; in our patients, this region was associated with ASD, heart defects, biliary tract dysfunction, and obesity. The frequencies of the pathological phenotypes in duplication carriers reported in the literature were calculated and compared with those in patients with 3q29 deletions. Most of the phenotypes were observed in both groups but were significantly less common among individuals with 3q29 duplications. Mirrored phenotypes in patients with duplications and deletions included overweight and weight deficit. Schizophrenia, generalized anxiety disorder, and recurrent ear infections were unique phenotypes of patients carrying deletions. Conclusion Chromosome 3q29 duplication syndrome is characterized by a complex genetic architecture and clinical polymorphism.https://doi.org/10.1002/mgg3.700473q29 deletion syndrome3q29 duplication syndromeBDH1minimal critical regionmirrored phenotypesunique phenotypes |
| spellingShingle | A. A. Kashevarova M. E. Lopatkina O. Yu. Vasilyeva D. A. Fedotov A. D. Lobanov E. A. Fonova I. Z. Zhalsanova A. A. Zarubin O. A. Salyukova E. O. Belyaeva V. V. Petrova E. G. Ravzhaeva A. A. Agafonova A. D. Cheremnykh N. B. Torkhova S. L. Vovk I. N. Lebedev Delineation of the Genetic Architecture and Clinical Polymorphism of 3q29 Duplication Syndrome: A Review of the Literature and a Report of Two Novel Patients With Single‐Gene BDH1 Duplications Molecular Genetics & Genomic Medicine 3q29 deletion syndrome 3q29 duplication syndrome BDH1 minimal critical region mirrored phenotypes unique phenotypes |
| title | Delineation of the Genetic Architecture and Clinical Polymorphism of 3q29 Duplication Syndrome: A Review of the Literature and a Report of Two Novel Patients With Single‐Gene BDH1 Duplications |
| title_full | Delineation of the Genetic Architecture and Clinical Polymorphism of 3q29 Duplication Syndrome: A Review of the Literature and a Report of Two Novel Patients With Single‐Gene BDH1 Duplications |
| title_fullStr | Delineation of the Genetic Architecture and Clinical Polymorphism of 3q29 Duplication Syndrome: A Review of the Literature and a Report of Two Novel Patients With Single‐Gene BDH1 Duplications |
| title_full_unstemmed | Delineation of the Genetic Architecture and Clinical Polymorphism of 3q29 Duplication Syndrome: A Review of the Literature and a Report of Two Novel Patients With Single‐Gene BDH1 Duplications |
| title_short | Delineation of the Genetic Architecture and Clinical Polymorphism of 3q29 Duplication Syndrome: A Review of the Literature and a Report of Two Novel Patients With Single‐Gene BDH1 Duplications |
| title_sort | delineation of the genetic architecture and clinical polymorphism of 3q29 duplication syndrome a review of the literature and a report of two novel patients with single gene bdh1 duplications |
| topic | 3q29 deletion syndrome 3q29 duplication syndrome BDH1 minimal critical region mirrored phenotypes unique phenotypes |
| url | https://doi.org/10.1002/mgg3.70047 |
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