Engelhardt, KR;
Xu, Y;
Grainger, A;
Germani Batacchi, MGC;
Swan, DJ;
Willet, JDP;
Abd Hamid, IJ;
... Hambleton, S; + view all
(2017)
Identification of Heterozygous Single- and Multi-exon Deletions in IL7R by Whole Exome Sequencing.
Journal of Clinical Immunology
, 37
pp. 42-50.
10.1007/s10875-016-0343-9.
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Abstract
PURPOSE: We aimed to achieve a retrospective molecular diagnosis by applying state-of-the-art genomic sequencing methods to past patients with T-B+NK+ severe combined immunodeficiency (SCID). We included identification of copy number variations (CNVs) by whole exome sequencing (WES) using the CNV calling method ExomeDepth to detect gene alterations for which routine Sanger sequencing analysis is not suitable, such as large heterozygous deletions. METHODS: Of a total of 12 undiagnosed patients with T-B+NK+ SCID, we analyzed eight probands by WES, using GATK to detect single nucleotide variants (SNVs) and small insertions and deletions (INDELs) and ExomeDepth to detect CNVs. RESULTS: We found heterozygous single- or multi-exon deletions in IL7R, a known disease gene for autosomal recessive T-B+NK+ SCID, in four families (seven patients). In three families (five patients), these deletions coexisted with a heterozygous splice site or nonsense mutation elsewhere in the same gene, consistent with compound heterozygosity. In our cohort, about a quarter of T-B+NK+ SCID patients (26%) had such compound heterozygous IL7R deletions. CONCLUSIONS: We show that heterozygous IL7R exon deletions are common in T-B+NK+ SCID and are detectable by WES. They should be considered if Sanger sequencing fails to detect homozygous or compound heterozygous IL7R SNVs or INDELs.
| Type: | Article |
|---|---|
| Title: | Identification of Heterozygous Single- and Multi-exon Deletions in IL7R by Whole Exome Sequencing |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s10875-016-0343-9 |
| Publisher version: | https://doi.org/10.1007/s10875-016-0343-9 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | IL7R, SCID, compound heterozygous, copy number variation, whole exome sequencing, Child, Child, Preschool, DNA Copy Number Variations, Exons, Female, Gene Expression, Heterozygote, Humans, INDEL Mutation, Lymphocyte Activation, Lymphocyte Subsets, Male, Polymorphism, Single Nucleotide, Receptors, Interleukin-7, Retrospective Studies, STAT5 Transcription Factor, Sequence Deletion, Severe Combined Immunodeficiency, Whole Exome Sequencing, Workflow |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10112415 |
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