Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological?
2010; Wiley; Volume: 31; Issue: 7 Linguagem: Inglês
10.1002/humu.21284
ISSN1098-1004
AutoresPrzemysław Szafrański, Christian P. Schaaf, Richard Person, Ian B. Gibson, Zhilian Xia, Sangeetha Mahadevan, Joanna Wiszniewska, Carlos A. Bacino, Seema R. Lalani, Lorraine Potocki, Sung-Hae L. Kang, Ankita Patel, Sau Wai Cheung, Frank J. Probst, Brett H. Graham, Marwan Shinawi, Arthur L. Beaudet, Paweł Stankiewicz,
Tópico(s)Genetics and Neurodevelopmental Disorders
ResumoHuman MutationVolume 31, Issue 7 p. 840-850 Research Article Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological?† Przemyslaw Szafranski, Przemyslaw Szafranski Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas Przemyslaw Szafranski and Christian P. Schaaf contributed equally to this work.Search for more papers by this authorChristian P. Schaaf, Christian P. Schaaf Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas Przemyslaw Szafranski and Christian P. Schaaf contributed equally to this work.Search for more papers by this authorRichard E. Person, Richard E. Person Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorIan B. Gibson, Ian B. Gibson Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorZhilian Xia, Zhilian Xia Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorSangeetha Mahadevan, Sangeetha Mahadevan Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorJoanna Wiszniewska, Joanna Wiszniewska Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorCarlos A. Bacino, Carlos A. Bacino Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorSeema Lalani, Seema Lalani Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorLorraine Potocki, Lorraine Potocki Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorSung-Hae Kang, Sung-Hae Kang Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorAnkita Patel, Ankita Patel Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorSau Wai Cheung, Sau Wai Cheung Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorFrank J. Probst, Frank J. Probst Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorBrett H. Graham, Brett H. Graham Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorMarwan Shinawi, Marwan Shinawi Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorArthur L. Beaudet, Arthur L. Beaudet Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorPawel Stankiewicz, Corresponding Author Pawel Stankiewicz [email protected] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas Department of Medical Genetics, Institute of Mother and Child, Warsaw, PolandDepartment of Molecular & Human Genetics, Baylor College of Medicine, One Baylor Plaza, Rm. R809, Houston, TX 77030Search for more papers by this author Przemyslaw Szafranski, Przemyslaw Szafranski Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas Przemyslaw Szafranski and Christian P. Schaaf contributed equally to this work.Search for more papers by this authorChristian P. Schaaf, Christian P. Schaaf Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas Przemyslaw Szafranski and Christian P. Schaaf contributed equally to this work.Search for more papers by this authorRichard E. Person, Richard E. Person Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorIan B. Gibson, Ian B. Gibson Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorZhilian Xia, Zhilian Xia Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorSangeetha Mahadevan, Sangeetha Mahadevan Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorJoanna Wiszniewska, Joanna Wiszniewska Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorCarlos A. Bacino, Carlos A. Bacino Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorSeema Lalani, Seema Lalani Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorLorraine Potocki, Lorraine Potocki Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorSung-Hae Kang, Sung-Hae Kang Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorAnkita Patel, Ankita Patel Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorSau Wai Cheung, Sau Wai Cheung Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorFrank J. Probst, Frank J. Probst Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorBrett H. Graham, Brett H. Graham Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorMarwan Shinawi, Marwan Shinawi Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorArthur L. Beaudet, Arthur L. Beaudet Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorPawel Stankiewicz, Corresponding Author Pawel Stankiewicz [email protected] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas Department of Medical Genetics, Institute of Mother and Child, Warsaw, PolandDepartment of Molecular & Human Genetics, Baylor College of Medicine, One Baylor Plaza, Rm. R809, Houston, TX 77030Search for more papers by this author First published: 24 June 2010 https://doi.org/10.1002/humu.21284Citations: 100 † Communicated by Jacques S. Beckmann AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract We have investigated four ∼1.6-Mb microduplications and 55 smaller 350–680-kb microduplications at 15q13.2–q13.3 involving the CHRNA7 gene that were detected by clinical microarray analysis. Applying high-resolution array-CGH, we mapped all 118 chromosomal breakpoints of these microduplications. We also sequenced 26 small microduplication breakpoints that were clustering at hotspots of nonallelic homologous recombination (NAHR). All four large microduplications likely arose by NAHR between BP4 and BP5 LCRs, and 54 small microduplications arose by NAHR between two CHRNA7-LCR copies. We identified two classes of ∼1.6-Mb microduplications and five classes of small microduplications differing in duplication size, and show that they duplicate the entire CHRNA7. We propose that size differences among small microduplications result from preexisting heterogeneity of the common BP4–BP5 inversion. Clinical data and family histories of 11 patients with small microduplications involving CHRNA7 suggest that these microduplications might be associated with developmental delay/mental retardation, muscular hypotonia, and a variety of neuropsychiatric disorders. 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