RT Journal Article
SR Electronic
T1 Somatic uniparental disomy with a rare <em>EFL1</em> variant causes Shwachman-Diamond syndrome through dysregulating ribosomal protein synthesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 483362
DO 10.1101/483362
A1 Sangmoon Lee
A1 Chang Hoon Shin
A1 Che Ry Hong
A1 Jun-Dae Kim
A1 Ah-Ra Kim
A1 Jawon Lee
A1 Oleksandr Kokhan
A1 Taekyeong Yoo
A1 Young Bae Sohn
A1 Ok-Hwa Kim
A1 Jung Min Ko
A1 Tae-Joon Cho
A1 Nathan T. Wright
A1 Suk-Won Jin
A1 Hyoung Jin Kang
A1 Hyeon Ho Kim
A1 Murim Choi
YR 2018
UL http://biorxiv.org/content/early/2018/12/06/483362.abstract
AB We present three unrelated Korean Shwachman-Diamond syndrome (SDS) patients that carry an incomplete but identical homozygous EFL1 p.Thr1069Ala variant due to a bone marrow-specific mosaic uniparental disomy (UPD) in chromosome 15. This rare variant is found in 0.017% of East Asians and is asymptomatic in a heterozygous status, but harbors a hypomorphic effect, leading to reduced 80S ribosome assembly of ribosomal protein (RP) transcripts. We propose a novel somatically-induced pathogenesis mechanism and EFL1 dysfunction that eventually leads to aberrant translational control and ribosomopathy.