Bone marrow failure syndrome caused by homozygous frameshift mutation in the ERCC6L2 gene

Abstract

Inherited bone marrow failure syndromes (IBMFS) are group of disorders that lead to inadequate production of blood cells. Mutations in genes involved in telomere maintenance, DNA repair, and the cell cycle cause IBMFS. ERCC6L2 gene mutations have been associated with bone marrow failure that includes developmental delay and microcephaly. We report two cases of bone marrow failure with no extra-hematopoietic manifestations in patients from unrelated families with a homozygous truncating mutation in ERCC6L2. Bone marrow failure without developmental delay or microcephaly with ERCC6L2 mutation has not been previously described.

Presentation of wild type and predicted mutated forms of ERCC6L2 protein in patients with inherited bone marrow failure syndrome. A) A full length ERCC6L2 protein consists of 1561 amino acids. The DEXDc domain binds ATP and Helicase domain catalyzes the DNA remodeling. B) The c. 1457del(p.(Ile486fs)) mutation, described in this study, results in premature stop codon, leading to truncation of the protein and total lack of helicase domain. C) and D) schematically describe the two truncating mutations described previously. C) by Tummala et al. Am J Hum Genet. 2014;94(2):246-256 and D) by Tummala et al. and Zhang et al., J Exp Med. 2016;213(6):1011-1028.

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