SLFN14 mutations underlie thrombocytopenia with excessive bleeding and platelet secretion defects

Fletcher, Sarah J.; Johnson, Benjamin C.; Lowe, Gillian; Bem, Danai; Drake, Sian; Lordkipanidzé, Marie; Guiu, Isabel Sánchez; Dawood, B; Rivera, José; Simpson, Michael A.; Daly, Mary E.; Jayashree, Muralidharan; Collins, Peter William; Watson, Steve P.; Morgan, Neil V.

doi:10.1172/jci80347

Cited by 78 publications

(91 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…WES and bioinformatics analysis were performed as described previously 8,15,16 ( Figure 1). The pathogenicity of variants was determined and called using the consensus guidelines as set out by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG guidelines).…”

Section: Whole Exome Sequencingmentioning

confidence: 99%

“…Seven variants have previously been published as part of two separate publications from the UK-GAPP study group. 8,15 Classification of the 28 variants occurring within the known IT-related genes, following the interpretation guidelines set out by Richards et al, 17 revealed four variants to be "pathogenic", 13 to be "likely pathogenic" and 11 to be of "uncertain significance". Variants classified as "pathogenic" were either already known to be a genetic cause of IT; ANKRD26; c.-126T>G in F2.I and MYH9; p.Arg1165Cys in F9.I, or were predicted to be loss-of-function variants in genes for which a loss of function is known to cause disease; FLI1; p.Asn331Thr fs*4, in F4.I and F4.II and RUNX1; pTrp79* in P12.I.…”

Section: Variants In Known Thrombocytopenia-causing Genesmentioning

confidence: 99%

See 1 more Smart Citation

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Johnson¹,

Lowe²,

Fütterer³

et al. 2016

Haematologica

121

135

View full text Add to dashboard Cite

Section: Whole Exome Sequencingmentioning

confidence: 99%

Section: Variants In Known Thrombocytopenia-causing Genesmentioning

confidence: 99%

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Johnson¹,

Lowe²,

Fütterer³

et al. 2016

Haematologica

121

135

View full text Add to dashboard Cite

“…5 Several new PFDs with less distinctive phenotypes have recently been identified by using high-throughput sequencing. [6][7][8] However, to date, these have only been reported in small numbers of pedigrees and are incompletely characterized.…”

Section: Introductionmentioning

confidence: 99%

Expanded repertoire of RASGRP2 variants responsible for platelet dysfunction and severe bleeding

Westbury

Canault

Greene

et al. 2017

Blood

View full text Add to dashboard Cite

show abstract

“…In this study, the presence of known genetic causes is ruled out by functional and genetic testing. The GAPP study recently showed that a platelet defect was identified in approximately 60% of the investigated participants (>500 patients) by using whole exome sequencing (WES) techniques (Fletcher et al , 2015; Watson et al , 2013). …”

mentioning

confidence: 99%

Application of whole‐exome sequencing to direct the specific functional testing and diagnosis of rare inherited bleeding disorders in patients from the Öresund Region, Scandinavia

et al. 2017

View full text Add to dashboard Cite

SummaryRare inherited bleeding disorders (IBD) are a common cause of bleeding tendency. To ensure a correct diagnosis, specialized laboratory analyses are necessary. This study reports the results of an upfront diagnostic strategy using targeted whole exome sequencing. In total, 156 patients with a significant bleeding assessment tool score participated in the study, of which a third had thrombocytopenia. Eighty‐seven genes specifically associated with genetic predisposition to bleeding were analysed by whole exome sequencing. Variants were classified according to the five‐tier scheme. We identified 353 germline variants. Eight patients (5%) harboured a known pathogenic variant. Of the 345 previously unknown variants, computational analyses predicted 99 to be significant. Further filtration according to the Mendelian inheritance pattern, resulted in 59 variants being predicted to be clinically significant. Moreover, 34% (20/59) were assigned as novel class 4 or 5 variants upon targeted functional testing. A class 4 or 5 variant was identified in 30% of patients with thrombocytopenia (14/47) versus 11% of patients with a normal platelet count (12/109) (P < 0·01). An IBD diagnosis has a major clinical impact. The genetic investigations detailed here extricated our patients from a diagnostic conundrum, thus demonstrating that continuous optimization of the diagnostic work‐up of IBD is of great benefit.

show abstract

SLFN14 mutations underlie thrombocytopenia with excessive bleeding and platelet secretion defects

Cited by 78 publications

References 17 publications

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Expanded repertoire of RASGRP2 variants responsible for platelet dysfunction and severe bleeding

Application of whole‐exome sequencing to direct the specific functional testing and diagnosis of rare inherited bleeding disorders in patients from the Öresund Region, Scandinavia

Contact Info

Product

Resources

About