Revertant somatic mosaicism by mitotic recombination in dyskeratosis congenita.

American Journal of Human Genetics
Marjolijn C J JongmansRoland P Kuiper

Abstract

Revertant mosaicism is an infrequently observed phenomenon caused by spontaneous correction of a pathogenic allele. We have observed such reversions caused by mitotic recombination of mutant TERC (telomerase RNA component) alleles in six patients from four families affected by dyskeratosis congenita (DC). DC is a multisystem disorder characterized by mucocutaneous abnormalities, dystrophic nails, bone-marrow failure, lung fibrosis, liver cirrhosis, and cancer. We identified a 4 nt deletion in TERC in a family with an autosomal-dominant form of DC. In two affected brothers without bone-marrow failure, sequence analysis revealed pronounced overrepresentation of the wild-type allele in blood cells, whereas no such skewing was observed in the other tissues tested. These observations suggest that this mosaic pattern might have resulted from somatic reversion of the mutated allele to the normal allele in blood-forming cells. SNP-microarray analysis on blood DNA from the two brothers indeed showed independent events of acquired segmental isodisomy of chromosome 3q, including TERC, indicating that the reversions must have resulted from mitotic recombination events. Subsequently, after developing a highly sensitive method of detecting m...Continue Reading

Citations

Oct 22, 2016·American Journal of Hematology·Nieves PerdigonesMonica Bessler
Jan 21, 2017·British Journal of Haematology·Natasha StanleyDaria V Babushok
Feb 9, 2017·Cellular and Molecular Life Sciences : CMLS·Young H LimKeith A Choate
Sep 3, 2017·Cold Spring Harbor Molecular Case Studies·Nicole G GriffinErin L Heinzen
Sep 3, 2020·Proceedings of the National Academy of Sciences of the United States of America·Luther DavisNancy Maizels
Jun 20, 2013·Postgraduate Medical Journal·Lars Anders ForsbergJan Piotr Dumanski
Jul 31, 2013·Clinical Genetics·J Y Hehir-KwaN de Leeuw
May 14, 2014·The Journal of Cell Biology·Brody HolohanJerry W Shay
Mar 16, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Elissa Furutani, Akiko Shimamura
Feb 14, 2017·The Journal of Clinical Investigation·Lindley MaryoungChristine Kim Garcia
Jul 15, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Víctor Martínez-GlezPablo Lapunzina
Jan 17, 2013·American Journal of Medical Genetics. Part a·Audrey PutouxDamien Sanlaville
Mar 17, 2015·The Journal of Clinical Investigation·Keith A ChoateRichard P Lifton
Jun 21, 2013·Expert Review of Hematology·Bari J Ballew, Sharon A Savage
Nov 12, 2016·Fly·Katarzyna Siudeja, Allison J Bardin
Oct 6, 2018·Journal of Medical Genetics·Aijie LiuYuehua Zhang
Jan 24, 2019·Blood·Alyssa L Kennedy, Akiko Shimamura
Jun 13, 2019·Nature Reviews. Genetics·Patrick RevyAlain Fischer
Dec 7, 2019·Hematology·Elissa Furutani, Akiko Shimamura
Jun 20, 2020·Blood·Luiz Fernando B CattoRodrigo T Calado
Feb 18, 2017·British Journal of Haematology·Talia Wegman-Ostrosky, Sharon A Savage
Aug 21, 2020·Blood·Marjolijn C Jongmans, Roland P Kuiper
Jan 4, 2013·Clinical Chemistry·Eva C Guinan, Suneet Agarwal
Jan 3, 2018·The Journal of Clinical Investigation·Christine Kim Garcia
Apr 2, 2015·Current Protocols in Human Genetics·Arleen D Auerbach
Mar 1, 2014·The Journal of Investigative Dermatology·Dimitra KiritsiAnna M G Pasmooij
Jan 14, 2020·Journal of Dermatological Science·Toshifumi Nomura
Feb 25, 2020·Hematology/oncology Clinics of North America·Kristen E Schratz, Amy E DeZern
Apr 23, 2020·Cell Stem Cell·Neha NagpalSuneet Agarwal
Aug 31, 2020·Molecular and Cellular Endocrinology·Sabina Domené, Horacio M Domené
Apr 4, 2021·International Journal of Molecular Sciences·Elena CrisàAndrea Patriarca
Jan 15, 2018·Differentiation; Research in Biological Diversity·Elena FioriniSimona Colla
May 7, 2014·The Journal of Allergy and Clinical Immunology·Huie JingHelen C Su
Jun 23, 2021·Blood Advances·Amy E DeZern, Jane E Churpek
Jul 15, 2021·British Journal of Haematology·Andrew D Hughes, Peter Kurre
Aug 19, 2021·Best Practice & Research. Clinical Haematology·Fernanda Gutierrez-RodriguesNeal S Young
Aug 4, 2021·The Journal of Clinical Investigation·Kristen E SchratzMary Armanios

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