Whole-gene CFTR sequencing combined with digital RT-PCR improves genetic diagnosis of cystic fibrosis

Viral infections are known to lead to serious respiratory complications in cystic fibrosis (CF) patients. Hypothesizing that CF patients were a population at high risk for severe respiratory complications from SARS-CoV-2 infection, we conducted a national study to describe the clinical expression of COVID-19 in French CF patients. This prospective observational study involves all 47 French CF centers caring for approximately 7500 CF patients. Between March 1st and June 30th 2020, 31 patients were diagnosed with COVID-19: 19 had positive SARS-CoV-2 RT-PCR in nasopharyngeal swabs; 1 had negative RT-PCR but typical COVID-19 signs on a CT scan; and 11 had positive SARS-CoV-2 serology. Fifteen were males, median (range) age was 31 (9–60) years, and 12 patients were living with a lung transplant. The majority of the patients had CF-related diabetes (n = 19, 61.3%), and a mild lung disease (n = 19, 65%, with percent-predicted forced expiratory volume in 1 s (ppFEV1) > 70). Three (10%) patients remained asymptomatic. For the 28 (90%) patients who displayed symptoms, most common symptoms at admission were fever (n = 22, 78.6%), fatigue (n = 14, 50%), and increased cough (n = 14, 50%). Nineteen were hospitalized (including 11 out of the 12 post-lung transplant patients), seven required oxygen therapy, and four (3 post-lung transplant patients) were admitted to an Intensive Care Unit (ICU). Ten developed complications (including acute respiratory distress syndrome in two post-lung transplant patients), but all recovered and were discharged home without noticeable short-term sequelae. Overall, French CF patients were rarely diagnosed with COVID-19. Further research should establish whether they were not infected or remained asymptomatic upon infection. In diagnosed cases, the short-term evolution was favorable with rare acute respiratory distress syndrome and no death. Post-lung transplant patients had more severe outcomes and should be monitored more closely.

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The Biology of Acute Promyelocytic Leukemia and Its Impact on Diagnosis and Treatment

Hematology ◽

10.1182/asheducation-2006.1.156 ◽

2006 ◽

Vol 2006 (1) ◽

pp. 156-161 ◽

Cited By ~ 49

Author(s):

Francesco Lo-Coco ◽

Emanuele Ammatuna

Keyword(s):

Acute Promyelocytic Leukemia ◽

Target Genes ◽

Low Cost ◽

Genetic Diagnosis ◽

Promyelocytic Leukemia ◽

Nuclear Staining ◽

Rt Pcr ◽

Treatment Type ◽

Related Phenotype ◽

Repressor Complex

Abstract Several genetic and phenotypic characteristics of acute promyelocytic leukemia (APL) blasts provide relevant targets and the rationale for tailored treatment. These include the PML/RARα fusion and the transcription co-repressor complex recruited at the promoter of target genes by the hybrid protein, the intense and homogeneous expression of the CD33 antigen, absence of multidrug resistance–related phenotype, and a frequently mutated and constitutively activated FLT3 receptor. Such genotypic and phenotypic features are targeted by agents currently in use in front-line therapy or at relapse (i.e., retinoids, arsenic trioxide, anthracyclines and anti-CD33 monoclonal antibodies), and by novel agents that may find a place in future treatments such as histone deacetylase and FLT3 inhibitors. The unique PML/RARα aberration serves as a molecular marker for rapid diagnosis and prediction of response to ATRA-and ATO-containing therapies. Methods for prompt and low-cost detection of this genetic abnormality, such as the analysis of PML nuclear staining, are extremely useful in clinical practice and could be adopted in countries with limited resources as a surrogate for rapid genetic diagnosis. Finally, PML/RARα monitoring through sensitive RT-PCR can be regarded as an integrating part of the overall treatment strategy in this disease, whereby the treatment type and intensity are modulated in patients at different risk of relapse according to RT-PCR status during follow-up. Because recent clinical studies suggest that most APL patients receiving intensive chemotherapy may be over-treated, longitudinal and stringent RT-PCR monitoring is becoming increasingly important to test the extent to which chemotherapy can be minimized in those presenting with low-risk disease.

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Preimplantation genetic diagnosis of cystic fibrosis (ΔF508)

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/0028-2243(95)02294-3 ◽

1996 ◽

Vol 65 (1) ◽

pp. 7-10 ◽

Cited By ~ 2

Author(s):

Asangla Ao ◽

Alan Handyside ◽

Robert M.L. Winston

Keyword(s):

Cystic Fibrosis ◽

Preimplantation Genetic Diagnosis ◽

Genetic Diagnosis

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Influenza Virus Detection Following Administration of Live-Attenuated Intranasal Influenza Vaccine in Children With Cystic Fibrosis and Their Healthy Siblings

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw187 ◽

2016 ◽

Vol 3 (4) ◽

Cited By ~ 2

Author(s):

Constantina Boikos ◽

Lawrence Joseph ◽

Christine Martineau ◽

Jesse Papenburg ◽

David Scheifele ◽

...

Keyword(s):

Cystic Fibrosis ◽

Small Sample Size ◽

Virus Detection ◽

Credible Interval ◽

Small Sample ◽

Influenza Viruses ◽

Study Cohort ◽

Rt Pcr ◽

Rna Detection

Abstract Background. We aimed to explore the detection profile of influenza viruses following live-attenuated intranasal influenza vaccination (LAIV) in children aged 2–19 years with and without cystic fibrosis (CF). Methods. Before the 2013–2014 influenza season, flocked nasal swabs were obtained before vaccination and 4 times in the week of follow-up from 76 participants (nCF: 57; nhealthy: 19). Influenza was detected by reverse transcription polymerase chain reaction (RT-PCR) assays. A Bayesian hierarchical logistic regression model was used to estimate the effect of CF status and age on influenza detection. Results. Overall, 69% of the study cohort shed influenza RNA during follow-up. The mean duration of RT-PCR detection was 2.09 days (95% credible interval [CrI]: 1.73–2.48). The odds of influenza RNA detection on day 1 following vaccination decreased with age in years (odds ratio [OR]: 0.82 per year; 95% CrI: 0.70–0.95), and subjects with CF had higher odds of influenza RNA detection on day 1 of follow-up (OR: 5.09; 95% CrI: 1.02–29.9). Conclusion. Despite the small sample size, our results indicate that LAIV vaccine strains are detectable during the week after LAIV, mainly in younger individuals and vaccinees with CF. It remains unclear whether recommendations for avoiding contact with severely immunocompromised patients should differ for these groups.

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