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Incidence and Carrier Frequency of CFTR Gene Mutations in Pregnancies With Echogenic Bowel in Nova Scotia and Prince Edward Island

Published:March 01, 2018DOI:https://doi.org/10.1016/j.jogc.2017.11.021

      Abstract

      Objective

      Fetal echogenic bowel (echogenic bowel) is associated with cystic fibrosis (CF), with a reported incidence ranging from 1% to 13%. Prenatal testing for CF in the setting of echogenic bowel can be done by screening parental or fetal samples for pathogenic CFTR variants. If only one pathogenic variant is identified, sequencing of the CFTR gene can be undertaken, to identify a second pathogenic variant not covered in the standard screening panel. Full gene sequencing, however, also introduces the potential to identify variants of uncertain significance (VUSs) that can create counselling challenges and cause parental anxiety. To provide accurate counselling for families in the study population, the incidence of CF associated with echogenic bowel and the carrier frequency of CFTR variants were investigated.

      Methods

      All pregnancies for which CF testing was undertaken for the indication of echogenic bowel (from Nova Scotia and Prince Edward Island) were identified (January 2007–July 2017). The CFTR screening and sequencing results were reviewed, and fetal outcomes related to CF were assessed.

      Results

      A total of 463 pregnancies with echogenic bowel were tested. Four were confirmed to be affected with CF, giving an incidence of 0.9% in this cohort. The carrier frequency of CF among all parents in the cohort was 5.0% (1 in 20); however, when excluding parents of affected fetuses, the carrier frequency for the population was estimated at 4.1% (1 in 25). CFTR gene sequencing identified an additional VUS in two samples.

      Conclusion

      The incidence of CF in pregnancies with echogenic bowel in Nova Scotia and Prince Edward Island is 0.9%, with an estimated population carrier frequency of 4.1%. These results provide the basis for improved counselling to assess the risk of CF in the pregnancy, after parental carrier screening, using Bayesian probability. Counselling regarding VUSs should be undertaken before gene sequencing.

      Résumé

      Objectif

      L'intestin échogène fœtal est associé à la fibrose kystique (FK), avec une incidence rapportée allant de 1 à 13 %. Le dépistage anténatal de la FK dans le contexte de l'intestin échogène peut se faire par l'analyse d'échantillons parentaux ou fœtaux visant à trouver des variants pathogènes du gène CFTR. Si un seul variant est détecté, le séquençage du gène CFTR peut être entrepris pour détecter un deuxième variant pathogène non couvert par les tests de dépistages standard. Le séquençage complet du gène risque toutefois de détecter des variants de signification incertaine (VSI) pouvant compliquer le counseling et causer de l'anxiété chez les parents. Afin de fournir des conseils avisés aux familles de la population à l'étude, nous nous sommes penchés sur l'incidence de la FK associée à l'intestin échogène et la fréquence de porteurs des variants du gène CFTR.

      Méthodologie

      Nous avons relevé toutes les grossesses pour lesquelles un dépistage de la FK a été entrepris en raison d'un intestin échogène (en Nouvelle-Écosse et à l'Île-du-Prince-Édouard, de janvier 2007 à juillet 2017). Puis, nous avons examiné les résultats de dépistage et de séquençage du gène CFTR et évalué les issues fœtales liées à la FK.

      Résultats

      Au total, 463 grossesses présentant un intestin échogène ont fait l'objet d'un dépistage. La présence de FK a été confirmée chez quatre fœtus, soit une incidence de 0,9 % dans cette cohorte. La fréquence de porteurs de FK parmi les parents de la cohorte était de 5,0 % (1 sur 20); cependant, lorsqu'on excluait les parents des fœtus atteints, la fréquence pour la population était estimée à 4,1 % (1 sur 25). Le séquençage du gène CFTR a permis de détecter un VSI supplémentaire dans deux échantillons.

      Conclusion

      L'incidence de la FK dans les grossesses présentant un intestin échogène en Nouvelle-Écosse et à l'Île-du-Prince-Édouard est de 0,9 %, et la fréquence de porteurs dans la population est estimée à 4,1 %. Ces résultats pourront servir à améliorer le counseling dans le but d'évaluer le risque de FK, après le dépistage des parents porteurs, à partir de la probabilité bayésienne. Un counseling concernant les VSI devrait être offert avant le séquençage.

      Key Words

      Abbreviations:

      ACMG (American College of Medical Genetics), CF (cystic fibrosis), FATC (Fetal Assessment and Treatment Centre), VUS (variant of uncertain significance)
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