Long-read sequencing is required for precision diagnosis of incontinentia pigmenti
Summary: Incontinentia pigmenti (IP) is caused by loss-of-function variants in IKBKG, with molecular genetic diagnosis complicated by a pseudogene. We describe seven individuals from three families with IP but negative clinical genetic testing in whom long-read sequencing identified causal variants,...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-07-01
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| Series: | HGG Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666247725000715 |
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| author | Monica H. Wojcik Robin D. Clark Abdallah F. Elias Casie A. Genetti Jill A. Madden Dana Simpson Linda Golkar Miranda P.G. Zalusky Angela L. Miller Araceli Rodriguez Joy Goffena Camille A. Dash Nikhita Damaraju Sophia B. Gibson Sophie H.R. Storz Zachary B. Anderson Jonas A. Gustafson Isabelle Thiffault Emily G. Farrow Tomi Pastinen Jasmine Lin Jennifer T. Huang Alan H. Beggs Pankaj B. Agrawal David T. Miller Danny E. Miller |
| author_facet | Monica H. Wojcik Robin D. Clark Abdallah F. Elias Casie A. Genetti Jill A. Madden Dana Simpson Linda Golkar Miranda P.G. Zalusky Angela L. Miller Araceli Rodriguez Joy Goffena Camille A. Dash Nikhita Damaraju Sophia B. Gibson Sophie H.R. Storz Zachary B. Anderson Jonas A. Gustafson Isabelle Thiffault Emily G. Farrow Tomi Pastinen Jasmine Lin Jennifer T. Huang Alan H. Beggs Pankaj B. Agrawal David T. Miller Danny E. Miller |
| author_sort | Monica H. Wojcik |
| collection | DOAJ |
| description | Summary: Incontinentia pigmenti (IP) is caused by loss-of-function variants in IKBKG, with molecular genetic diagnosis complicated by a pseudogene. We describe seven individuals from three families with IP but negative clinical genetic testing in whom long-read sequencing identified causal variants, including one family with the common exon 4–10 deletion not identified by conventional clinical genetic testing. Concurrent methylation analysis explained disease severity in one individual who died from neurologic complications, identified a mosaic variant in an individual with an atypical presentation, and confirmed skewed X chromosome inactivation in an XXY individual. |
| format | Article |
| id | doaj-art-646577decf394de38dce15b1eafb34cd |
| institution | OA Journals |
| issn | 2666-2477 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | HGG Advances |
| spelling | doaj-art-646577decf394de38dce15b1eafb34cd2025-08-20T02:22:01ZengElsevierHGG Advances2666-24772025-07-016310046810.1016/j.xhgg.2025.100468Long-read sequencing is required for precision diagnosis of incontinentia pigmentiMonica H. Wojcik0Robin D. Clark1Abdallah F. Elias2Casie A. Genetti3Jill A. Madden4Dana Simpson5Linda Golkar6Miranda P.G. Zalusky7Angela L. Miller8Araceli Rodriguez9Joy Goffena10Camille A. Dash11Nikhita Damaraju12Sophia B. Gibson13Sophie H.R. Storz14Zachary B. Anderson15Jonas A. Gustafson16Isabelle Thiffault17Emily G. Farrow18Tomi Pastinen19Jasmine Lin20Jennifer T. Huang21Alan H. Beggs22Pankaj B. Agrawal23David T. Miller24Danny E. Miller25Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USADivision of Clinical Genetics, Loma Linda University Children’s Hospital and Loma Linda University School of Medicine, Loma Linda, CA, USADepartment of Medical Genetics, Shodair Children’s Hospital, Helena, MT, USA; Division of Biological Sciences, University of Montana, Missoula, MT, USA; Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT, USABoston Children’s Hospital and Harvard Medical School, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USABoston Children’s Hospital and Harvard Medical School, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USARandall Children’s Hospital, Portland, OR, USADepartment of Dermatology, Loma Linda University School of Medicine, Loma Linda, CA, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children’s Hospital, Seattle, WA, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children’s Hospital, Seattle, WA, USADivision of Clinical Genetics, Loma Linda University Children’s Hospital and Loma Linda University School of Medicine, Loma Linda, CA, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children’s Hospital, Seattle, WA, USABoston Children’s Hospital and Harvard Medical School, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children’s Hospital, Seattle, WA, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children’s Hospital, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children’s Hospital, Seattle, WA, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children’s Hospital, Seattle, WA, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children’s Hospital, Seattle, WA, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USAChildren’s Mercy Hospital, Kansas City, MO, USAChildren’s Mercy Hospital, Kansas City, MO, USAChildren’s Mercy Hospital, Kansas City, MO, USABoston Children’s Hospital and Harvard Medical School, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USABoston Children’s Hospital and Harvard Medical School, Boston, MA, USABoston Children’s Hospital and Harvard Medical School, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USABoston Children’s Hospital and Harvard Medical School, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USABoston Children’s Hospital and Harvard Medical School, Boston, MA, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children’s Hospital, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA; Brotman Baty Institute for Precision Medicine, University of Washington, Seattle, WA, USA; Corresponding authorSummary: Incontinentia pigmenti (IP) is caused by loss-of-function variants in IKBKG, with molecular genetic diagnosis complicated by a pseudogene. We describe seven individuals from three families with IP but negative clinical genetic testing in whom long-read sequencing identified causal variants, including one family with the common exon 4–10 deletion not identified by conventional clinical genetic testing. Concurrent methylation analysis explained disease severity in one individual who died from neurologic complications, identified a mosaic variant in an individual with an atypical presentation, and confirmed skewed X chromosome inactivation in an XXY individual.http://www.sciencedirect.com/science/article/pii/S2666247725000715incontinentia pigmentiIKBKGlong-read sequencingpseudogenestructural variationmethylation |
| spellingShingle | Monica H. Wojcik Robin D. Clark Abdallah F. Elias Casie A. Genetti Jill A. Madden Dana Simpson Linda Golkar Miranda P.G. Zalusky Angela L. Miller Araceli Rodriguez Joy Goffena Camille A. Dash Nikhita Damaraju Sophia B. Gibson Sophie H.R. Storz Zachary B. Anderson Jonas A. Gustafson Isabelle Thiffault Emily G. Farrow Tomi Pastinen Jasmine Lin Jennifer T. Huang Alan H. Beggs Pankaj B. Agrawal David T. Miller Danny E. Miller Long-read sequencing is required for precision diagnosis of incontinentia pigmenti HGG Advances incontinentia pigmenti IKBKG long-read sequencing pseudogene structural variation methylation |
| title | Long-read sequencing is required for precision diagnosis of incontinentia pigmenti |
| title_full | Long-read sequencing is required for precision diagnosis of incontinentia pigmenti |
| title_fullStr | Long-read sequencing is required for precision diagnosis of incontinentia pigmenti |
| title_full_unstemmed | Long-read sequencing is required for precision diagnosis of incontinentia pigmenti |
| title_short | Long-read sequencing is required for precision diagnosis of incontinentia pigmenti |
| title_sort | long read sequencing is required for precision diagnosis of incontinentia pigmenti |
| topic | incontinentia pigmenti IKBKG long-read sequencing pseudogene structural variation methylation |
| url | http://www.sciencedirect.com/science/article/pii/S2666247725000715 |
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