Premium
A founder variant in the South Asian population leads to a high prevalence of FANCL Fanconi anemia cases in India
Author(s) -
Donovan Frank X.,
Solanki Avani,
Mori Minako,
Chavan Niranjan,
George Merin,
C Selvaa Kumar,
Okuno Yusuke,
Muramastsu Hideki,
Yoshida Kenichi,
Shimamoto Akira,
TakaoriKondo Akifumi,
Yabe Hiromasa,
Ogawa Seishi,
Kojima Seiji,
Yabe Miharu,
RamanagoudrBhojappa Ramanagouda,
Smogorzewska Agata,
Mohan Sheila,
Rajendran Aruna,
Auerbach Arleen D.,
Takata Minoru,
Chandrasekharappa Settara C.,
Vundinti Babu Rao
Publication year - 2020
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23914
Subject(s) - library science , population , family medicine , biology , medicine , environmental health , computer science
Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure, predisposition to cancer, and congenital abnormalities. FA is caused by pathogenic variants in any of 22 genes involved in the DNA repair pathway responsible for removing interstrand crosslinks. FANCL, an E3 ubiquitin ligase, is an integral component of the pathway, but patients affected by disease‐causing FANCL variants are rare, with only nine cases reported worldwide. We report here a FANCL founder variant, anticipated to be synonymous, c.1092G>A;p.K364=, but demonstrated to induce aberrant splicing, c.1021_1092del;p.W341_K364del, that accounts for the onset of FA in 13 cases from South Asia, 12 from India and one from Pakistan. We comprehensively illustrate the pathogenic nature of the variant, provide evidence for a founder effect, and propose including this variant in genetic screening of suspected FA patients in India and Pakistan, as well as those with ancestry from these regions of South Asia.