Somatic mosaicism of an intragenic FANCB duplication in both fibroblast and peripheral blood cells observed in a Fanconi anemia patient leads to milder phenotype

ConclusionUnlike sequence point variants, intragenic duplications are difficult to precisely define, accurately quantify, and may be very unstable, challenging the proper diagnosis. The reversion of genomic duplication to the WT allele results in somatic mosaicism and may explain the relatively milder phenotype displayed by the FA‐B patient described here.

Fanconi anemia patients harboring X‐linked FANCB pathogenic variants usually present with severe congenital malformations. We report a patient exhibiting a milder phenotype with an intragenic duplication of exon 3, and its flanking regions, in FANCB. Somatic mosaicism was observed in the peripheral blood DNA of the proband and his mother, as well as in the fibroblast DNA from the proband. The duplication appears to be unstable and, to a variable extent, reverts back to wild‐type FANCB causing somatic mosaicism, explaining the milder phenotype.

Source: Molecular Genetics & Genomic Medicine - November 1, 2017 Category: Genetics & Stem Cells Authors: Rajalakshmi S. Asur, Danielle C. Kimble, Francis P. Lach, Moonjung Jung, Frank X. Donovan, Aparna Kamat, Raymond J. Noonan, James W. Thomas, Morgan Park, Peter Chines, Adrianna Vlachos, Arleen D. Auerbach, Agata Smogorzewska, Settara C. Chandrasekharappa Tags: ORIGINAL ARTICLE Source Type: research