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Christina Zeitz 1
Auteur
Christelle Michiels 1
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Marion Neuillé 2
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Christoph Friedburg 3
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Jean-François Deleuze 12
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Dror Sharon 13
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Isabelle Drumare 14
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Sabine Defoort-Dhellemmes 14
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Elfride de Baere 15
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Bart Leroy 16, 17, 18
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Xavier Zanlonghi 19
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Ingele Casteels 20
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Hélène Dollfus 27, 28
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Yaumara Perdomo-Trujillo
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Celine Faure 29
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Charlotte Reiff
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Eberhart Zrenner 32
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Bernhard Jurklies 33
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Birgit Lorenz 3
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José-Alain Sahel 4, 34, 1, 35
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Isabelle Audo 1, 4, 36
Auteur
Inherited retinal disorders (IRD) represent clinically and genetically heterogeneous diseases. To date, pathogenic variants have been identified in ~260 genes. Albeit that many genes are implicated in IRD, for 30-50% of the cases, the gene defect is unknown. These cases may be explained by novel gene defects, by overlooked structural variants, by variants in intronic, promoter or more distant regulatory regions, and represent synonymous variants of known genes contributing to the dysfunction of the respective proteins. Patients with one subgroup of IRD, namely incomplete congenital stationary night blindness (icCSNB), show a very specific phenotype. The major cause of this condition is the presence of a hemizygous pathogenic variant in CACNA1F. A comprehensive study applying direct Sanger sequencing of the gene-coding regions, exome and genome sequencing applied to a large cohort of patients with a clinical diagnosis of icCSNB revealed indeed that seven of the 189 CACNA1F-related cases have intronic and synonymous disease-causing variants leading to missplicing as validated by minigene approaches. These findings highlight that gene-locus sequencing may be a very efficient method in detecting disease-causing variants in clinically well-characterized patients with a diagnosis of IRD, like icCSNB.
UNIV-ANGERS | CEA | CEA-UPSAY | UNIV-VALENCIENNES | UNIV-MONTPELLIER | JACOB | UNIV-EVRY | U968 | SU-MEDECINE | GENOSCOPE | CNRS | BS | SITE-ALSACE | UNIV-PARIS5 | UP-SANTE | MITOVASC | CEA-DRF | USPC | SORBONNE-UNIVERSITE | UNIV-PARIS-SACLAY | UNIV-PARIS | SU-TI