Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders – updated European recommendations

Dequeker, Elisabeth; Stuhrmann, Manfred; Morris, Michael A.; Casals, Teresa; Castellani, Carlo; Claustres, Mireille; Cuppens, Harry; Georges, Marie des; Férec, Claude; Maçek, Milan; Pignatti, Pierfranco; Scheffer, Hans; Schwartz, Marianne; Witt, Michał; Schwarz, Martin; Girodon, Emmanuelle

doi:10.1038/ejhg.2008.136

Cited by 211 publications

(179 citation statements)

References 67 publications

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“…For example, the I148T variant no longer has the qualification of a pathogenic mutation but is still included in the commercial kits (eg, InnoLipa, Innogenetics). 33 Prudence is therefore always essential in molecular genetics.…”

Section: Newborn Screening For Cf In Polandmentioning

confidence: 99%

Newborn screening for cystic fibrosis: Polish 4 years’ experience with CFTR sequencing strategy

Sobczyńska-Tomaszewska¹,

Ołtarzewski²,

Czerska³

et al. 2012

Eur J Hum Genet

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Newborn screening for cystic fibrosis (NBS CF) in Poland was started in September 2006. Summary from 4 years' experience is presented in this study. The immunoreactive trypsin/DNA sequencing strategy was implemented. The group of 1 212 487 newborns were screened for cystic fibrosis during the programme. We identified a total of 221 CF cases during this period, including, 4 CF cases were reported to be omitted by NBS CF. Disease incidence in Poland based on the programme results was estimated as 1/4394 and carrier frequency as 1/33. The frequency of the F508del was similar (62%) to population data previously reported. This strategy allowed us to identify 29 affected infants with rare genotypes. The frequency of some mutations (eg, 2184insA, K710X) was assessed in Poland for the first time. Thus, sequencing assay seems to be accurate method for screening programme using blood spots in the Polish population.

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Section: Newborn Screening For Cf In Polandmentioning

confidence: 99%

Newborn screening for cystic fibrosis: Polish 4 years’ experience with CFTR sequencing strategy

Sobczyńska-Tomaszewska¹,

Ołtarzewski²,

Czerska³

et al. 2012

Eur J Hum Genet

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“…Their decisions are based on expert consensus and best practice guidelines, and depend on the clinical indication in the case. [13][14][15][16] Two assessors independently evaluate genotypes and interpretation in the submitted reports. Results are also discussed during an assessment meeting.…”

Section: Context and Setting Of The Studymentioning

confidence: 99%

“…Interpretation could additionally be influenced by external factors such as the availability of best practice guidelines and publications. [13][14][15] Second, the presence in clinical reports of all investigated interpretation elements improved over the years. Two elements increased remarkably more (430%) than others: stating the need to test the parents of a CF patient to confirm homozygosity or compound heterozygosity (need for qualification of the genotype) and Interpretation in CF laboratory reports S Berwouts et al mentioning the possibility of testing the relatives.…”

Section: Principal Findingsmentioning

confidence: 99%

Improvement of interpretation in cystic fibrosis clinical laboratory reports: longitudinal analysis of external quality assessment data

et al. 2012

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Participation in external quality assessment (EQA) is a key element of quality assurance in medical laboratories. In genetics EQA, both genotyping and interpretation are assessed. We aimed to analyse changes in the completeness of interpretation in clinical laboratory reports of the European cystic fibrosis EQA scheme and to investigate the effect of the number of previous participations, laboratory accreditation/certification status, setting and test volume. We distributed similar versions of mock clinical cases to eliminate the influence of the difficulty of the clinical question on interpretation performance: a cystic fibrosis patient (case 1) and a cystic fibrosis carrier (case 2). We then performed a retrospective longitudinal study of reports over a 6-year period from 298 participants for case 1 (2004, 2008, 2009) and from 263 participants for case 2 (2006, 2008, 2009). The number of previous participations had a positive effect on the interpretation score (Po0.0001), whereas the laboratory accreditation/certification status, setting and test volume had no effect. Completeness of interpretation improved over time. The presence of the interpretation element 'requirement for studying the parents to qualify the genotype' increased most (from 49% in 2004 to 93% in 2009). We still observed room for improvement for elements that concerned offering testing for familial mutations in relatives and prenatal/preimplantation diagnosis (16% and 24% omission, respectively, for case 1 in 2009). Overall, regular participation in external quality assessment contributes to improved interpretation in reports, with potential value for quality of care for patients and families by healthcare professionals involved in genetic testing.

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“…However, group 2 variants can cause CFTR-related symptoms when present in trans in a group 1 variant in a compound heterozygous genotype. 4,5,[22][23][24][25][26] The partial damaging effects of group 2 variants on the CFTR gene product have been demonstrated in functional and biochemical analyses.…”

Section: Group 2 Cftr Variants Display Disease-contributing Potentialmentioning

confidence: 99%

“…26 Included in this group are 11 nonsense, 26 frameshift, and 14 invariant splice-site variants. In addition, we tested each missense variant with both the PolyPhen-2 and PROVEAN tools.…”

Section: Group 3 Cftr Variants Have Not Been Reported In Disease Genomentioning

confidence: 99%

Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk

Lim¹,

Silver²,

Silver³

et al. 2016

Genetics in Medicine

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Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders – updated European recommendations

Cited by 211 publications

References 67 publications

Newborn screening for cystic fibrosis: Polish 4 years’ experience with CFTR sequencing strategy

Newborn screening for cystic fibrosis: Polish 4 years’ experience with CFTR sequencing strategy

Improvement of interpretation in cystic fibrosis clinical laboratory reports: longitudinal analysis of external quality assessment data

Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk

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