Somatic genetic rescue in <i>ZCCHC8</i> -associated telomere biology disorders

S Sophie de Tocqueville (1Laboratory of Genome Dynamics in Human Diseases, Equipe Labellisée Ligue contre le Cancer “LIGUE 2023”, INSERM UMR 1163, Imagine Institute, Paris, France) F Flavia Donaires (4Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil) N Nicholas DeCleene (5Department of Pediatrics, Baylor College of Medicine, Houston, TX) I Ibrahima Ba (7Assistance Publique des Hôpitaux de Paris, Hôpital Bichat, Service de Génétique, Université Paris Diderot, Paris, France) M Mina Nouri (1Laboratory of Genome Dynamics in Human Diseases, Equipe Labellisée Ligue contre le Cancer “LIGUE 2023”, INSERM UMR 1163, Imagine Institute, Paris, France) L Laëtitia Kermasson (1Laboratory of Genome Dynamics in Human Diseases, Equipe Labellisée Ligue contre le Cancer “LIGUE 2023”, INSERM UMR 1163, Imagine Institute, Paris, France) M Malika Chelbi (7Assistance Publique des Hôpitaux de Paris, Hôpital Bichat, Service de Génétique, Université Paris Diderot, Paris, France) E Emmanuel Bergot T Thierry Leblanc (Immuno-hématologie Pédiatrique, Hôpital Robert-Debré, Université Paris-Cité, Paris) R Raphael Borie (10Service de Pneumologie, Allergologie et Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Centre de référence constitutif des maladies pulmonaires rares, Paris, France) Q Quentin Philippot (10Service de Pneumologie, Allergologie et Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Centre de référence constitutif des maladies pulmonaires rares, Paris, France) E Elise Antone (11Pneumopôle d’Aunis, La Rochelle, France) G Grégoire Prévot E Elodie Blanchard (13Service de Pneumologie, CHU de Bordeaux, Bordeaux, France) B Boris Keren (14Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Département de Génétique, Hôpital Pitié-Salpêtrière, Paris, France) E Elodie Lainey (15Hematology Laboratory, Robert Debré Hospital-Assistance Publique-Hôpitaux de Paris, INSERM UMR 1131-Hematology University Institute-Denis Diderot School of Medicine, Paris, France) M Marilia Catto (4Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil) B Barbara Santana (4Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil) S Settara C. Chandrasekharappa F Frank X. Donovan L Luiz Fernando Bazzo Catto (17Translational Stem Cell Biology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD) I Isabelle Callebaut N Neal S. Young C Carine Halfon-Domenech (20Institute of Pediatric Hematology-Oncology, University of Lyon 1, Hospices Civils de Lyon, Lyon, France) R Rodrigo T. Calado (4Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil) A Alison A. Bertuch (5Department of Pediatrics, Baylor College of Medicine, Houston, TX) F Fernanda Gutierrez-Rodrigues C Caroline Kannengiesser (7Assistance Publique des Hôpitaux de Paris, Hôpital Bichat, Service de Génétique, Université Paris Diderot, Paris, France) P Patrick Revy (1Laboratory of Genome Dynamics in Human Diseases, Equipe Labellisée Ligue contre le Cancer “LIGUE 2023”, INSERM UMR 1163, Imagine Institute, Paris, France)

Abstract

Abstract We show that somatic genetic rescue is frequent in telomere biology disorders (TBDs) caused by germ line ZCCHC8 variants. Our results highlight the critical intrinsic role of ZCCHC8 in human hematopoiesis and a potential mechanism for disease modification in TBDs.

Article Details

Journal Blood
Volume / Issue Vol. 147, Issue 9
Published February 26, 2026
Pages 998-1003
ISSN 0006-4971
Publisher Elsevier BV

Journal Info

Blood

Elsevier BV

ISSN: 0006-4971 Health Sciences

Authors (29)

S

Sophie de Tocqueville

1Laboratory of Genome Dynamics in Human Diseases, Equipe Labellisée Ligue contre le Cancer “LIGUE 2023”, INSERM UMR 1163, Imagine Institute, Paris, France

F

Flavia Donaires

4Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

N

Nicholas DeCleene

5Department of Pediatrics, Baylor College of Medicine, Houston, TX

I

Ibrahima Ba

7Assistance Publique des Hôpitaux de Paris, Hôpital Bichat, Service de Génétique, Université Paris Diderot, Paris, France

M

Mina Nouri

1Laboratory of Genome Dynamics in Human Diseases, Equipe Labellisée Ligue contre le Cancer “LIGUE 2023”, INSERM UMR 1163, Imagine Institute, Paris, France

L

Laëtitia Kermasson

1Laboratory of Genome Dynamics in Human Diseases, Equipe Labellisée Ligue contre le Cancer “LIGUE 2023”, INSERM UMR 1163, Imagine Institute, Paris, France

M

Malika Chelbi

7Assistance Publique des Hôpitaux de Paris, Hôpital Bichat, Service de Génétique, Université Paris Diderot, Paris, France

E

Emmanuel Bergot

T

Thierry Leblanc

Immuno-hématologie Pédiatrique, Hôpital Robert-Debré, Université Paris-Cité, Paris

R

Raphael Borie

10Service de Pneumologie, Allergologie et Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Centre de référence constitutif des maladies pulmonaires rares, Paris, France

Q

Quentin Philippot

10Service de Pneumologie, Allergologie et Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Centre de référence constitutif des maladies pulmonaires rares, Paris, France

E

Elise Antone

11Pneumopôle d’Aunis, La Rochelle, France

G

Grégoire Prévot

E

Elodie Blanchard

13Service de Pneumologie, CHU de Bordeaux, Bordeaux, France

B

Boris Keren

14Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Département de Génétique, Hôpital Pitié-Salpêtrière, Paris, France

E

Elodie Lainey

15Hematology Laboratory, Robert Debré Hospital-Assistance Publique-Hôpitaux de Paris, INSERM UMR 1131-Hematology University Institute-Denis Diderot School of Medicine, Paris, France

M

Marilia Catto

4Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

B

Barbara Santana

4Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

S

Settara C. Chandrasekharappa

F

Frank X. Donovan

L

Luiz Fernando Bazzo Catto

17Translational Stem Cell Biology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD

I

Isabelle Callebaut

N

Neal S. Young

C

Carine Halfon-Domenech

20Institute of Pediatric Hematology-Oncology, University of Lyon 1, Hospices Civils de Lyon, Lyon, France

R

Rodrigo T. Calado

4Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

A

Alison A. Bertuch

5Department of Pediatrics, Baylor College of Medicine, Houston, TX

F

Fernanda Gutierrez-Rodrigues

C

Caroline Kannengiesser

7Assistance Publique des Hôpitaux de Paris, Hôpital Bichat, Service de Génétique, Université Paris Diderot, Paris, France

P

Patrick Revy

1Laboratory of Genome Dynamics in Human Diseases, Equipe Labellisée Ligue contre le Cancer “LIGUE 2023”, INSERM UMR 1163, Imagine Institute, Paris, France