Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Geoffroy, V; Stoetzel, C; Scheidecker, S; Schaefer, E; Perrault, I; Bär, S; Kröll, A; Delbarre, M; Antin, M; Leuvrey, AS; Henry, C; Blanché, H; Decker, E; Kloth, K; Klaus, G; Mache, C; Martin-Coignard, D; McGinn, S; Boland, A; Deleuze, JF; Friant, S; Saunier, S; Rozet, JM; Bergmann, C; Dollfus, H; Muller, J.
Whole-genome sequencing in patients with ciliopathies uncovers a novel recurrent tandem duplication in IFT140.
HUM MUTAT. 2018; 39(7): 983-992.
Doi: 10.1002/humu.23539
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- Co-Autor*innen der Med Uni Graz
- Mache Christoph
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- Abstract:
- Ciliopathies represent a wide spectrum of rare diseases with overlapping phenotypes and a high genetic heterogeneity. Among those, IFT140 is implicated in a variety of phenotypes ranging from isolated retinis pigmentosa to more syndromic cases. Using whole-genome sequencing in patients with uncharacterized ciliopathies, we identified a novel recurrent tandem duplication of exon 27-30 (6.7 kb) in IFT140, c.3454-488_4182+2588dup p.(Tyr1152_Thr1394dup), missed by whole-exome sequencing. Pathogenicity of the mutation was assessed on the patients' skin fibroblasts. Several hundreds of patients with a ciliopathy phenotype were screened and biallelic mutations were identified in 11 families representing 12 pathogenic variants of which seven are novel. Among those unrelated families especially with a Mainzer-Saldino syndrome, eight carried the same tandem duplication (two at the homozygous state and six at the heterozygous state). In conclusion, we demonstrated the implication of structural variations in IFT140-related diseases expanding its mutation spectrum. We also provide evidences for a unique genomic event mediated by an Alu-Alu recombination occurring on a shared haplotype. We confirm that whole-genome sequencing can be instrumental in the ability to detect structural variants for genomic disorders. © 2018 Wiley Periodicals, Inc.
- Find related publications in this database (using NLM MeSH Indexing)
- Alu Elements - genetics
- Carrier Proteins - genetics
- Cerebellar Ataxia - genetics
- Cerebellar Ataxia - pathology
- Ciliopathies - genetics
- Ciliopathies - pathology
- Databases, Genetic -
- Exons - genetics
- Female -
- Heterozygote -
- Homozygote -
- Humans -
- Male -
- Mutation - genetics
- Pedigree -
- Phenotype -
- Retinitis Pigmentosa - genetics
- Retinitis Pigmentosa - pathology
- Whole Genome Sequencing -
- Find related publications in this database (Keywords)
- Alu-mediated recombination
- copy number variation
- IFT140
- Mainzer-Saldino syndrome
- structural variation
- tandem duplication
- whole-genome sequencing