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Mol Genet Genomic Med. 2019 Feb;7(2):e00521. doi: 10.1002/mgg3.521. Epub 2018 Nov 28.

Retrotransposon insertion as a novel mutational event in Bardet-Biedl syndrome.

Author information

1
Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
2
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
3
The Centre for Applied Genomics, Hospital for Sick Children, Toronto, Ontario, Canada.
4
Ophthalmology and Vision Sciences, Hospital for Sick Children, Toronto, Ontario, Canada.

Abstract

BACKGROUND:

Bardet-Biedl syndrome (BBS) is an autosomal recessive pleiotropic disorder of the primary cilia that leads to severe visual loss in the teenage years. Approximately 80% of BBS cases are explained by mutations in one of the 21 identified genes. Documented causative mutation types include missense, nonsense, copy number variation (CNV), frameshift deletions or insertions, and splicing variants.

METHODS:

Whole genome sequencing was performed on a patient affected with BBS for whom no mutations were identified using clinically approved genetic testing of the known genes. Analysis of the WGS was done using internal protocols and publicly available algorithms. The phenotype was defined by retrospective chart review.

RESULTS:

We document a female affected with BBS carrying the most common BBS1 mutation (BBS1: Met390Arg) on the maternal allele and an insertion of a ~1.7-kb retrotransposon in exon 13 on the paternal allele. This retrotransposon insertion was not automatically annotated by the standard variant calling protocols used. This novel variant was identified by visual inspection of the alignment file followed by specific genome analysis with an available algorithm for transposable elements.

CONCLUSION:

This report documents a novel mutation type associated with BBS and highlights the importance of systematically performing transposon detection analysis on WGS data of unsolved cases.

KEYWORDS:

BBS1 ; BBS; Bardet-Biedl syndrome; SVA; ciliopathy; human genome; mutation; repetitive element; transposable element

PMID:
30484961
PMCID:
PMC6393654
DOI:
10.1002/mgg3.521
[Indexed for MEDLINE]
Free PMC Article

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