Predictive Prenatal Diagnosis for Infantile-onset Inflammatory Bowel Disease Because of Interleukin-10 Signalling Defects

Ziqing Ye; Wenhui Hu; Bingbing Wu; Yueping Zhang; Caixia Lei; Isabelle Williams; Dror S Shouval; Hirokazu Kanegane; Kyung Mo Kim; Lissy de Ridder; Neil Shah; Galina Ling; Baruch Yerushalmi; Daniel Kotlarz; Scott Snapper; Ruth Horn; Christoph Klein; Aleixo M Muise; Ying Huang; Holm H Uhlig

doi:10.1097/MPG.0000000000002937

Predictive Prenatal Diagnosis for Infantile-onset Inflammatory Bowel Disease Because of Interleukin-10 Signalling Defects

J Pediatr Gastroenterol Nutr. 2021 Feb 1;72(2):276-281. doi: 10.1097/MPG.0000000000002937.

Authors

Ziqing Ye^{1

2}, Wenhui Hu¹, Bingbing Wu³, Yueping Zhang⁴, Caixia Lei⁴, Isabelle Williams², Dror S Shouval⁵, Hirokazu Kanegane⁶, Kyung Mo Kim⁷, Lissy de Ridder⁸, Neil Shah⁹, Galina Ling¹⁰, Baruch Yerushalmi¹⁰, Daniel Kotlarz¹¹, Scott Snapper¹², Ruth Horn¹³, Christoph Klein¹¹, Aleixo M Muise^{14

15}, Ying Huang¹, Holm H Uhlig^{2

16

17

18}

Affiliations

¹ Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China.
² Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
³ Key Lab of Birth Defects, Children's Hospital of Fudan University, Shanghai, China.
⁴ Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
⁵ Pediatric Gastroenterology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramag Gan, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁶ Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
⁷ Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children's Hospital 88, Olympic-Ro 43 Gil, Songpa-Gu, Seoul, Korea.
⁸ Department of Paediatric Gastroenterology, Erasmus University Medical Center Sophia Children's Hospital, Rotterdam, The Netherlands.
⁹ Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
¹⁰ Pediatric Gastroenterology Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
¹¹ Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
¹² Boston Children's Hospital and Harvard Medical School, Boston, MA.
¹³ Wellcome Centre for Ethics and Humanities and the Ethox Centre, University of Oxford, UK.
¹⁴ SickKids Inflammatory Bowel Disease Centre and Cell Biology Program, Research Institute.
¹⁵ Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
¹⁶ Department of Pediatrics.
¹⁷ Biomedical Research Center, University of Oxford, Oxford, United Kingdom.
¹⁸ Translational Gastroenterology Unit.

Abstract

Objectives: Advances in genetic technologies provide opportunities for patient care and ethical challenges. Clinical care of patients with rare Mendelian disorders is often at the forefront of those developments. Whereas in classical polygenic inflammatory bowel disease (IBD), the predictive value of genetic variants is very low, predictive prenatal genetic diagnosis can inform families at high risk of severe genetic disorders. Patients with IL-10 signalling defects because of pathogenic variants in IL10RA, Il10RB, and IL10 develop severe infantile onset inflammatory bowel disease that is completely penetrant and has a high morbidity and substantial mortality despite treatment.

Methods: We performed a survey among tertiary specialist paediatric centers of 10 countries on the utilization of predictive prenatal genetic diagnosis in IL-10 signalling defects. We retrospectively report prenatal genetics in a series of 8 families.

Results: International variation in legislation, guidelines, expert opinion, as well as cultural and religious background of families and clinicians results in variable utilization of preimplantation and prenatal genetic testing for IL-10 signalling defects. Eleven referrals for prenatal diagnosis for IL-10 signalling defects were identified across 4 countries. We report on 8 families who underwent prenatal preimplantation monogenic testing after in vitro fertilization (n = 2) and/or by amniocentesis/chorion villus sampling (n = 6). A genetic diagnosis was established in 1 foetus and excluded in 7 foetuses (all IL10RA variants).

Conclusions: Prenatal genetic testing for IL10R-defects is feasible, yet the legal and ethical considerations are complex and controversial. In some countries, predictive genetics for IL-10-related signalling defects is entering clinical practice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age of Onset
Child
Female
Humans
Inflammatory Bowel Diseases* / diagnosis
Inflammatory Bowel Diseases* / genetics
Interleukin-10* / genetics
Pregnancy
Prenatal Diagnosis
Retrospective Studies

Substances

Interleukin-10

Abstract

Publication types

MeSH terms

Substances

Grants and funding