Novel Alu insertion in the ZEB2 gene causing Mowat-Wilson syndrome
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Novel Alu insertion in the ZEB2 gene causing Mowat-Wilson syndrome. / Barington, Maria; Bak, Mads; Kjartansdóttir, Kristín Rós; Hansen, Thomas van Overeem; Birkedal, Ulf; Østergaard, Elsebet; Hove, Hanne Buciek.
I: American Journal of Medical Genetics, Part A, Bind 194, Nr. 8, e63581, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Novel Alu insertion in the ZEB2 gene causing Mowat-Wilson syndrome
AU - Barington, Maria
AU - Bak, Mads
AU - Kjartansdóttir, Kristín Rós
AU - Hansen, Thomas van Overeem
AU - Birkedal, Ulf
AU - Østergaard, Elsebet
AU - Hove, Hanne Buciek
N1 - Publisher Copyright: © 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
PY - 2024
Y1 - 2024
N2 - Alu elements are short, interspersed elements located throughout the genome, playing a role in human diversity, and occasionally causing genetic diseases. Here, we report a novel Alu insertion causing Mowat-Wilson syndrome, a rare neurodevelopmental disorder, in an 8-year-old boy displaying the typical clinical features for Mowat-Wilson syndrome. The variant was not initially detected in genome sequencing data, but through deep phenotyping, which pointed to only one plausible candidate gene, manual inspection of genome sequencing alignment data enabled us to identify a de novo heterozygous Alu insertion in exon 8 of the ZEB2 gene. Nanopore long-read sequencing confirmed the Alu insertion, leading to the formation of a premature stop codon and likely haploinsufficiency of ZEB2. This underscores the importance of deep phenotyping and mobile element insertion analysis in uncovering genetic causes of monogenic disorders as these elements might be overlooked in standard next-generation sequencing protocols.
AB - Alu elements are short, interspersed elements located throughout the genome, playing a role in human diversity, and occasionally causing genetic diseases. Here, we report a novel Alu insertion causing Mowat-Wilson syndrome, a rare neurodevelopmental disorder, in an 8-year-old boy displaying the typical clinical features for Mowat-Wilson syndrome. The variant was not initially detected in genome sequencing data, but through deep phenotyping, which pointed to only one plausible candidate gene, manual inspection of genome sequencing alignment data enabled us to identify a de novo heterozygous Alu insertion in exon 8 of the ZEB2 gene. Nanopore long-read sequencing confirmed the Alu insertion, leading to the formation of a premature stop codon and likely haploinsufficiency of ZEB2. This underscores the importance of deep phenotyping and mobile element insertion analysis in uncovering genetic causes of monogenic disorders as these elements might be overlooked in standard next-generation sequencing protocols.
KW - Alu
KW - AluYa5
KW - mobile element insertion analysis
KW - Mowat-Wilson syndrome
KW - SINE
KW - ZEB2
U2 - 10.1002/ajmg.a.63581
DO - 10.1002/ajmg.a.63581
M3 - Journal article
C2 - 38600862
AN - SCOPUS:85190438547
VL - 194
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 8
M1 - e63581
ER -
ID: 389509611