B9D1 is revealed as a novel Meckel syndrome (MKS) gene by targeted exon-enriched next-generation sequencing and deletion analysis

Hopp, Katharina; Heyer, Christina M.; Hommerding, Cynthia J.; Henke, Susan A.; Sundsbak, Jamie L.; Patel, S; Patel, P.G.; Consugar, Mark; Czarnecki, Peter G.; Gliem, Troy J.; Torres, Vicente E.; Rossetti, Sandro; Harris, Peter C.

doi:10.1093/hmg/ddr151

Cited by 80 publications

(60 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Two major commercial products for PCR-based target enrichment are RainDance's RainStorm (microdroplet-based) and Fluidigm's Access Array (microfluidicbased). Their applications in the context of NGS have successfully identified diseasecausing mutations for diagnostic testing [38][39][40].…”

Section: Targeted Sequencingmentioning

confidence: 99%

Next-generation sequencing in the clinic: Promises and challenges

et al. 2013

View full text Add to dashboard Cite

The advent of next generation sequencing (NGS) technologies has revolutionized the field of genomics, enabling fast and cost-effective generation of genome-scale sequence data with exquisite resolution and accuracy. Over the past years, rapid technological advances led by academic institutions and companies have continued to broaden NGS applications from research to the clinic. A recent crop of discoveries have highlighted the medical impact of NGS technologies on Mendelian and complex diseases, particularly cancer. However, the everincreasing pace of NGS adoption presents enormous challenges in terms of data processing, storage, management and interpretation as well as sequencing quality control, which hinder the translation from sequence data into clinical practice. In this review, we first summarize the technical characteristics and performance of current NGS platforms. We further highlight advances in the applications of NGS technologies towards the development of clinical diagnostics and therapeutics. Common issues in NGS workflows are also discussed to guide the selection of NGS platforms and pipelines for specific research purposes.

show abstract

Section: Targeted Sequencingmentioning

confidence: 99%

Next-generation sequencing in the clinic: Promises and challenges

et al. 2013

View full text Add to dashboard Cite

show abstract

“…29,30 This case also had a second missense mutation in B9D1 resulting in an amino-acid change predicted to be benign in one transcript and situated in the 3′ UTR of most other transcripts. The function of this alternative transcript or impact on 3′ UTR functioning is unknown at the moment.…”

Section: Non-mendelian Inheritance and B9d1mentioning

confidence: 99%

Joubert syndrome: genotyping a Northern European patient cohort

et al. 2015

View full text Add to dashboard Cite

Joubert syndrome (JBS) is a rare neurodevelopmental disorder belonging to the group of ciliary diseases. JBS is genetically heterogeneous, with 420 causative genes identified to date. A molecular diagnosis of JBS is essential for prediction of disease progression and genetic counseling. We developed a targeted next-generation sequencing (NGS) approach for parallel sequencing of 22 known JBS genes plus 599 additional ciliary genes. This method was used to genotype a cohort of 51 well-phenotyped Northern European JBS cases (in some of the cases, Sanger sequencing of individual JBS genes had been performed previously). Altogether, 21 of the 51 cases (41%) harbored biallelic pathogenic mutations in known JBS genes, including 14 mutations not previously described. Mutations in C5orf42 (12%), TMEM67 (10%), and AHI1 (8%) were the most prevalent. C5orf42 mutations result in a purely neurological Joubert phenotype, in one case associated with postaxial polydactyly. Our study represents a population-based cohort of JBS patients not enriched for consanguinity, providing insight into the relative importance of the different JBS genes in a Northern European population. Mutations in C5orf42 are relatively frequent (possibly due to a Dutch founder mutation) and mutations in CEP290 are underrepresented compared with international cohorts. Furthermore, we report a case with heterozygous mutations in CC2D2A and B9D1, a gene associated with the more severe Meckel-Gruber syndrome that was recently published as a potential new JBS gene, and discuss the significance of this finding.

show abstract

“…Whereas many studies are designed to identify genetic variation of protein-coding genes in a genome-wide manner (whole exome sequencing), there are also applications where a focus on specific genomic intervals or gene sets is required. For example, in the past year alone, there have been studies identifying variants linked to Meckel syndrome 2 and Fanconi's Anemia. 3 In clinical settings, where NGS is used to examine specific gene panels, and sample numbers are high, it is more cost-effective and time-efficient to target, capture, and sequence only the genomic regions of interest.…”

Section: Introductionmentioning

confidence: 99%