Identity-by-descent–guided mutation analysis and exome sequencing in consanguineous families reveals unusual clinical and molecular findings in retinal dystrophy

Coppieters, Frauke; Schil, Kristof Van; Bauwens, Miriam; Verdin, Hannah; Jaegher, Annelies De; Syx, Delfien; Sante, Tom; Lefever, Steve; Abdelmoula, Nouha Bouayed; Depasse, Fanny; Casteels, Ingele; Ravel, Thomy de; Meire, Françoise; Leroy, Bart P.; Baere, Elfride De

doi:10.1038/gim.2014.24

Cited by 52 publications

(33 citation statements)

References 37 publications

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“…It has become a powerful tool for elucidating complete mutation profiles for heterogeneous diseases. 27,28 In this study we developed a new capture panel to comprehensively screen 164 known IRD genes. Using a group of 179 unrelated patients with IRD, we successfully identified pathological mutations in 99 patients (55.3%).…”

Section: Discussionmentioning

confidence: 99%

Genotype–phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing

Huang

et al. 2015

Genetics in Medicine

183

126

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Purpose: Inherited retinal dystrophy (IRD) is a leading cause of blindness worldwide. Because of extreme genetic heterogeneity, the etiology and genotypic spectrum of IRD have not been clearly defined, and there is limited information on genotype-phenotype correlations. The purpose of this study was to elucidate the mutational spectrum and genotype-phenotype correlations of IRD. Methods:We developed a targeted panel of 164 known retinal disease genes, 88 candidate genes, and 32 retina-abundant microRNAs, used for exome sequencing. A total of 179 Chinese families with IRD were recruited. Results:In 99 unrelated patients, a total of 124 mutations in known retinal disease genes were identified, including 79 novel mutations (detection rate, 55.3%). Moreover, novel genotype-phenotype correlations were discovered, and phenotypic trends noted. Three cases are reported, including the identification of AHI1 as a novel candidate gene for nonsyndromic retinitis pigmentosa. Conclusion:This study revealed novel genotype-phenotype correlations, including a novel candidate gene, and identified 124 genetic defects within a cohort with IRD . The identification of novel genotype-phenotype correlations and the spectrum of mutations greatly enhance the current knowledge of IRD phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments of IRD patients.

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Section: Discussionmentioning

confidence: 99%

Genotype–phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing

Huang

et al. 2015

Genetics in Medicine

183

126

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“…Plink software, integrated in ViVar, identified homozygous regions of > 1 Mb, which were ranked according to their length and the number of SNPs, as described. 14 Only homozygous regions unique to the index case were selected. The presence of relevant known DSD genes was excluded using BioMart filtering.…”

Section: Genetic Studiesmentioning

confidence: 99%

Biallelic and monoallelic ESR2 variants associated with 46,XY disorders of sex development

Baetens

Güran

Mendonça

et al. 2018

Genetics in Medicine

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Purpose: Disorders or differences of sex development (DSDs) are rare congenital conditions characterized by atypical sex development. Despite advances in genomic technologies, the molecular cause remains unknown in 50% of cases.Methods: Homozygosity mapping and whole-exome sequencing revealed an ESR2 variant in an individual with syndromic 46,XY DSD. Additional cases with 46,XY DSD underwent whole-exome sequencing and targeted next-generation sequencing of ESR2. Functional characterization of the identified variants included luciferase assays and protein structure analysis. Gonadal ESR2 expression was assessed in human embryonic data sets and immunostaining of estrogen receptor-β (ER-β) was performed in an 8-week-old human male embryo.

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“…[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] It is estimated that more than 230 novel rare disease genes have been discovered to date using WES. 11 Several new NSHLcausative genes have also recently been revealed via WES, including GPSM2, DNMT1, BDP1, ELMOD3, TNC, GRXCR2, and ADCY1.…”

Section: Introductionmentioning

confidence: 99%

Identification of OSBPL2 as a novel candidate gene for progressive nonsyndromic hearing loss by whole-exome sequencing

Xing

Yao

et al. 2015

Genetics in Medicine

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Identity-by-descent–guided mutation analysis and exome sequencing in consanguineous families reveals unusual clinical and molecular findings in retinal dystrophy

Cited by 52 publications

References 37 publications

Genotype–phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing

Genotype–phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing

Biallelic and monoallelic ESR2 variants associated with 46,XY disorders of sex development

Identification of OSBPL2 as a novel candidate gene for progressive nonsyndromic hearing loss by whole-exome sequencing

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