{Reference Type}: Journal Article
{Title}: Whole-genome sequencing in patients with ciliopathies uncovers a novel recurrent tandem duplication in IFT140.
{Author}: 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;
{Journal}: Hum Mutat
{Volume}: 39
{Issue}: 7
{Year}: 07 2018
{Factor}: 4.7
{DOI}: 10.1002/humu.23539
{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.