Cystic Fibrosis in the African Diaspora

Stewart, Cheryl; Pepper, Michael Sean

doi:10.1513/annalsats.201606-481fr

Cited by 31 publications

(42 citation statements)

References 37 publications

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“…It is important to mention that of the five patients with the variants identified in this study, three have African ancestry, one has Latin European ancestry and one is unaware of the origin of the grandparents. In addition, the three mutations, G85E, A559T and R117H, in heterozygosis with the rearrangements found in this work, are part of the African Diaspora as observed in the study by Stewart and Pepper ().…”

Section: Discussionsupporting

confidence: 76%

Identification of a novel large deletion and other copy number variations in theCFTRgene in patients with Cystic Fibrosis from a multiethnic population

Martins

Campos

Moreira

et al. 2019

Molec Gen & Gen Med

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Background Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene ( CFTR ). There are over 2000 different pathogenic and non‐pathogenic variants described in association with a broad clinical heterogeneity. The most common types of mutations in this gene are single nucleotide substitutions or small deletions and insertions. However, large rearrangements, such as large duplications or deletions, are also a possible cause of CF; these variations are rarely tested in routine screenings, and much of them remain unidentified in some populations, especially those with high ethnic heterogeneity. Methods The present study utilized the Multiplex Ligation‐dependent Probe Amplification (MLPA) technique for the detection of duplications and deletions in 165 CF patients from the Rio de Janeiro State (Brazil), which after extensive mutational screening, still exhibited one or two unidentified CF alleles. Results Five patients with alterations in MLPA signals were detected. After validation, we identified three copy number variations, one large duplication (CFTRdup2‐3) and two large deletions (CFTRdel25‐26 and CFTRdel25‐27‐CTTNBP2). Two detected deletions were not validated. They were false positives caused by a small deletion of 18 base pairs (232del18) and a point mutation (S168L) in the probe binding site. Conclusion Our results highlight the importance of screening for large rearrangements in CF cases with no or only one CFTR mutation defined.

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Section: Discussionsupporting

confidence: 76%

Identification of a novel large deletion and other copy number variations in theCFTRgene in patients with Cystic Fibrosis from a multiethnic population

Martins

Campos

Moreira

et al. 2019

Molec Gen & Gen Med

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“…This is key given that implicit bias linking CF to Caucasians only may lead to delayed diagnosis, and continued attention should be paid to early genetic diagnosis in this group. 27 However, our data also demonstrate that malnutrition and stunting remain a concern, with 12% of infants falling below a z-score of −2 for both weight and height at the end of the time period studied. The BONUS study also found stunting in a smaller cohort of newborn screened infants.…”

Section: Discussionmentioning

confidence: 48%

“…Weight outcomes appear to be improving significantly for black infants. This is key given that implicit bias linking CF to Caucasians only may lead to delayed diagnosis, and continued attention should be paid to early genetic diagnosis in this group …”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes in U.S. infants with cystic fibrosis from 2001 to 2012

Hoch

Sontag

Scarbro

et al. 2018

Pediatric Pulmonology

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Background All 50 United States implemented newborn screening (NBS) for cystic fibrosis (CF) by 2010. The purpose of this study was to evaluate trends over the decade when NBS became universal to determine current rates of malnutrition, stunting, and infection rates in U.S. infants with CF. Methods Annual data were obtained on infants with CF up to 24 months of age diagnosed between 2001 and 2010 in the CF Foundation Patient Registry (CFFPR), in both the years of and after diagnosis, including method of diagnosis, demographics, and growth parameters and microbiology. Results Data were obtained on 8178 infants diagnosed with CF. The percentage of infants diagnosed by NBS increased from 15% in 2001‐83% in 2012 (P < 0.001). Mean weight, length, and weight‐for‐length z‐scores in the year of diagnosis increased from 2001 to 2012 (Wt z‐score 2001: −1.32 (SD 1.41), 2012: −0.72 (SD 1.12); Ht z‐score 2001: −1.32 (SD 1.57), 2012 −0.60 (SD 1.21); Wt/Ht Z score 2001: −0.54 (SD 1.18), 2012: 0.06 (SD 1.05); P < 0.001 for each). The proportion of infants on pancreatic enzymes decreased from 94% in 2001‐83% in 2012 (P < 0.0001). Pseudomonas aeruginosa culture positivity in the diagnosis year decreased significantly (27% in 2001, 15% in 2012, P < 0.001). Conclusions Nationwide implementation of CF NBS is temporally associated with significant improvements in growth outcomes and reductions in P. aeruginosa infections. Current rates of malnutrition, stunting, and airway infection present a target for early intervention and quality improvement efforts.

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“…6 Even among investigations of Latino populations, there have been limited efforts to describe the genetic profile of CF in the Caribbean. 7 There is considerable genetic heterogeneity between Latino populations and within the Caribbean. 8 In this study, full genetic sequencing of CFTR was done in Dominican and Puerto Rican patients with CF to describe the spectrum of CFTR variants.…”

Section: Discussionmentioning

confidence: 99%

“…CFTR variants are population‐specific and the spectrum of known CFTR variants is based largely on investigations of White populations . Even among investigations of Latino populations, there have been limited efforts to describe the genetic profile of CF in the Caribbean . There is considerable genetic heterogeneity between Latino populations and within the Caribbean …”

Section: Introductionmentioning

confidence: 99%

Identification of CFTR variants in Latino patients with cystic fibrosis from the Dominican Republic and Puerto Rico

Zeiger

McGarry

Mak

et al. 2019

Pediatric Pulmonology

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Background In cystic fibrosis (CF), the spectrum and frequency of CFTR variants differ by geography and race/ethnicity. CFTR variants in White patients are well‐described compared with Latino patients. No studies of CFTR variants have been done in patients with CF in the Dominican Republic or Puerto Rico. Methods CFTR was sequenced in 61 Dominican Republican patients and 21 Puerto Rican patients with CF and greater than 60 mmol/L sweat chloride. The spectrum of CFTR variants was identified and the proportion of patients with 0, 1, or 2 CFTR variants identified was determined. The functional effects of identified CFTR variants were investigated using clinical annotation databases and computational prediction tools. Results Our study found 10% of Dominican patients had two CFTR variants identified compared with 81% of Puerto Rican patients. No CFTR variants were identified in 69% of Dominican patients and 10% of Puerto Rican patients. In Dominican patients, there were 19 identified CFTR variants, accounting for 25 out of 122 disease alleles (20%). In Puerto Rican patients, there were 16 identified CFTR variants, accounting for 36 out of 42 disease alleles (86%) in Puerto Rican patients. Thirty CFTR variants were identified overall. The most frequent variants for Dominican patients were p.Phe508del and p.Ala559Thr and for Puerto Rican patients were p.Phe508del, p.Arg1066Cys, p.Arg334Trp, and p.I507del. Conclusions In this first description of the CFTR variants in patients with CF from the Dominican Republic and Puerto Rico, there was a low detection rate of two CFTR variants after full sequencing with the majority of patients from the Dominican Republic without identified variants.

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Cystic Fibrosis in the African Diaspora

Cited by 31 publications

References 37 publications

Identification of a novel large deletion and other copy number variations in theCFTRgene in patients with Cystic Fibrosis from a multiethnic population

Identification of a novel large deletion and other copy number variations in theCFTRgene in patients with Cystic Fibrosis from a multiethnic population

Clinical outcomes in U.S. infants with cystic fibrosis from 2001 to 2012

Identification of CFTR variants in Latino patients with cystic fibrosis from the Dominican Republic and Puerto Rico

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