Prenatal Ultrasound Suspicion of Cystic Fibrosis in a Multiethnic Population: Is Extensive CFTR Genotyping Needed?

Abstract

In families without a Cystic Fibrosis (CF) history, fetal ultrasound bowel abnormalities can unexpectedly reveal the disease. Isolated or in association, the signs can be fetal bowel hyperechogenicity, intestinal loop dilatation and non-visualization of fetal gallbladder. In these cases, search for CF transmembrane conductance regulator (CFTR) gene mutations is part of the recommended diagnostic practices, with a search for frequent mutations according to ethnicity, and, in case of the triad of signs, with an exhaustive study of the gene. However, the molecular diagnosis remains a challenge in populations without well-known frequent pathogenic variants. We present a multiethnic cohort of 108 pregnancies with fetal bowel abnormalities in which the parents benefited from an exhaustive study of the CFTR gene. We describe the new homozygous p.Cys1410* mutation in a fetus of African origin. We did not observe the most frequent p.Phe508del mutation in our cohort but evidenced variants undetected by our frequent mutations kit. Thanks to the progress of sequencing techniques and despite the difficulties of interpretation occasionally encountered, we discuss the need to carry out a comprehensive CFTR study in all patients in case of fetal bowel abnormalities.

Prenatal Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Promising Way to Change the Impact of Cystic Fibrosis

“…In a recent meta-analysis, CF was found in 2.2% of cases with fetal hyperechogenic bowel [14]. The specificity of these ultrasonographic signs of CF is higher if a combination of them is detected [15, 16]. If these findings are observed in prenatal ultrasound, offering parental CF carrier testing is recommended.…”

Hyperechogenic fetal bowel: Current evidence‐based prenatal diagnosis and management

“…Nevertheless the diagnosis of CF among fetuses presenting fetal bowel anomalies still remains challenging, due to the huge number of CFTR gene mutations, and this is the reason why performing exhaustive CFTR study in all patients is always indicated. 40,41 4 | OTHERS…”

A comprehensive review of cystic fibrosis in Africa and Asia

“…Nevertheless, awareness is still inadequate in many countries where sweat screening and genetic testing tools are unavailable, especially in the identification of atypical manifestation and different variant spectrum ( Cui et al, 2020 ). Furthermore, the existing mutational diagnostic (panel) kits are not suitable for the non-Caucasian populations, resulting in a false-negative test and difficulty in the detection of variants specific to these regions/countries ( Mekki et al, 2021 , Mayer Lacrosniere et al, 2021 ). This and the Caucasian allied misconception, might be some of the reasons behind the underdiagnosed or misdiagnosed CF cases in these concerned regions, leading to CF being diagnosed as another common phenocopy illness.…”

“…This includes Africa ( De Boeck, 2020 ) and Asia ( Banjar et al, 2021 ). According to CF registries in many of the European countries, it is evident that immigrants from both Africa and Asia have been diagnosed with CF especially in the UK, US, and France ( Mekki et al, 2021 ). More studies have also reported CF cases in Africa and Asia, with some rare and novel mutational variants specific to some ethnic groups ( Mathew et al, 2021 ).…”