Congenital hypoplastic bone marrow failure associated with a de novo partial deletion of the MECOM gene at 3q26.2

TY - JOUR

T1 - Congenital hypoplastic bone marrow failure associated with a de novo partial deletion of the MECOM gene at 3q26.2

AU - Kjeldsen, Eigil

AU - Veigaard, Christopher

AU - Aggerholm, Anni

AU - Hasle, Henrik

N1 - Copyright © 2017. Published by Elsevier B.V.

PY - 2018/5/20

Y1 - 2018/5/20

N2 - Congenital hypoplastic bone marrow failure is a rare condition in neonates. The genetics and mechanisms behind are largely obscure. Here we characterize a neonate presenting with congenital thrombocytopenia and anemia. During the first 2-4 weeks after birth the neonate developed severe neutropenia while the lymphoid lineages were unaffected. The neonate was without dysmorphic signs. A de novo mono-allelic constitutional microdeletion of 175.1 kb at 3q26.2 affecting exon 2 of MECOM, involving MDS1 but not EVI1, was identified as the only copy number alteration by oligo-based array-CGH analysis. Expression analysis showed profoundly reduced expression of multiple MECOM transcripts in the bone marrow cells. Whole exome sequencing detected no pathogenic mutations in genes known to be associated with inherited bone marrow failure syndromes. The patient was successfully treated with hematopoietic stem cell transplantation at 5 months of age. Interstitial deletions encompassing the 3q26.2 region are very rare. A literature search revealed two previous cases with microdeletions involving this region, and the cases were associated with congenital thrombocytopenia and anemia, but unaffected lymphopoiesis. Together these data indicate that MECOM may be important for normal myeloid hematopoiesis in humans but dispensable for lymphoid differentiation. We suggest that partial deletion in MECOM may be a primary event associated with congenital pancytopenia.

AB - Congenital hypoplastic bone marrow failure is a rare condition in neonates. The genetics and mechanisms behind are largely obscure. Here we characterize a neonate presenting with congenital thrombocytopenia and anemia. During the first 2-4 weeks after birth the neonate developed severe neutropenia while the lymphoid lineages were unaffected. The neonate was without dysmorphic signs. A de novo mono-allelic constitutional microdeletion of 175.1 kb at 3q26.2 affecting exon 2 of MECOM, involving MDS1 but not EVI1, was identified as the only copy number alteration by oligo-based array-CGH analysis. Expression analysis showed profoundly reduced expression of multiple MECOM transcripts in the bone marrow cells. Whole exome sequencing detected no pathogenic mutations in genes known to be associated with inherited bone marrow failure syndromes. The patient was successfully treated with hematopoietic stem cell transplantation at 5 months of age. Interstitial deletions encompassing the 3q26.2 region are very rare. A literature search revealed two previous cases with microdeletions involving this region, and the cases were associated with congenital thrombocytopenia and anemia, but unaffected lymphopoiesis. Together these data indicate that MECOM may be important for normal myeloid hematopoiesis in humans but dispensable for lymphoid differentiation. We suggest that partial deletion in MECOM may be a primary event associated with congenital pancytopenia.

KW - Aplastic anemia

KW - Congenital microdeletion

KW - Hematopoiesis

KW - MDS1-EVI1

KW - aCGH

UR - http://www.scopus.com/inward/record.url?scp=85043296550&partnerID=8YFLogxK

U2 - 10.1016/j.gene.2018.02.061

DO - 10.1016/j.gene.2018.02.061

M3 - Journal article

C2 - 29496554

SN - 0378-1119

VL - 656

SP - 86

EP - 96

JO - Gene

JF - Gene

ER -