| Literature DB >> 31513304 |
Frank X Donovan1, Avani Solanki2, Minako Mori3,4, Niranjan Chavan2, Merin George2, Selvaa Kumar C5, Yusuke Okuno6, Hideki Muramastsu7, Kenichi Yoshida8, Akira Shimamoto9, Akifumi Takaori-Kondo4, Hiromasa Yabe10, Seishi Ogawa8, Seiji Kojima7, Miharu Yabe10, Ramanagouda Ramanagoudr-Bhojappa1, Agata Smogorzewska11, Sheila Mohan12, Aruna Rajendran13, Arleen D Auerbach14, Minoru Takata3, Settara C Chandrasekharappa1, Babu Rao Vundinti2.
Abstract
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.Entities:
Keywords: FANCL; Fanconi anemia; India; South Asia; founder variant
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Year: 2019 PMID： 31513304 PMCID： PMC7362330 DOI： 10.1002/humu.23914
Source DB: PubMed Journal: Hum Mutat ISSN： 1059-7794 Impact factor: 4.700