Candidate Predisposition Variants in Kaposi Sarcoma as Detected by Whole-Genome Sequencing

Sanni J Rinne; Lauri J Sipilä; Päivi Sulo; Emmanuelle Jouanguy; Vivien Béziat; Laurent Abel; Jean-Laurent Casanova; Nima Parvaneh; Kamran Balighi; Emma Guttman-Yassky; Ronit Sarid; Lauri A Aaltonen; Mervi Aavikko

doi:10.1093/ofid/ofz337

Candidate Predisposition Variants in Kaposi Sarcoma as Detected by Whole-Genome Sequencing

Open Forum Infect Dis. 2019 Jul 17;6(10):ofz337. doi: 10.1093/ofid/ofz337. eCollection 2019 Oct.

Authors

Sanni J Rinne^{1

2}, Lauri J Sipilä^{1

2}, Päivi Sulo^{1

2}, Emmanuelle Jouanguy^{3

4

5}, Vivien Béziat^{3

4

5}, Laurent Abel^{3

4

5}, Jean-Laurent Casanova^{3

4

5

6

7}, Nima Parvaneh^{8

9}, Kamran Balighi^{10

11}, Emma Guttman-Yassky^{12

13}, Ronit Sarid¹⁴, Lauri A Aaltonen^{1

2}, Mervi Aavikko^{1

2}

Affiliations

¹ Applied Tumor Genomics Research Program and, Helsinki, Finland.
² Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.
³ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-1163, Paris, France.
⁴ University Paris Descartes, Imagine Institute, Paris, France.
⁵ St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York.
⁶ Howard Hughes Medical Institute, New York, New York.
⁷ Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, Paris, France.
⁸ Division of Allergy and Clinical Immunology, Department of Pediatrics, , Tehran, Iran.
⁹ Research Center for Immunodeficiencies, Tehran, Iran.
¹⁰ Department of Dermatology, Razi Hospital, and, Tehran, Iran.
¹¹ Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran.
¹² Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
¹³ Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York.
¹⁴ The Mina and Everard Goodman Faculty of Life Sciences & Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, Israel.

Abstract

Familial clustering of classic Kaposi sarcoma (CKS) is rare with, approximately 100 families reported to date. We studied 2 consanguineous families, 1 Iranian and 1 Israeli, with multiple cases of adult CKS and without overt underlying immunodeficiency. We performed genome-wide linkage analysis and whole-genome sequencing to discover the putative genetic cause for predisposition. A 9-kb homozygous intronic deletion in RP11-259O2.1 in the Iranian family and 2 homozygous variants, 1 in SCUBE2 and the other in CDHR5, in the Israeli family were identified as possible candidates. The presented variants provide a robust starting point for validation in independent samples.

Keywords: CDHR5; RP11-259O2.1; SCUBE2; classic Kaposi sarcoma; genetic linkage; genetic predisposition; whole-genome sequencing.