Identification and Characterization of a Rare Exon 22 Duplication in CFTR in Two Families DOI Open Access
Simone Ahting,

Constance Henn,

Maike vom Hove

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4487 - 4487

Published: May 8, 2025

Accurate genetic diagnosis is essential for appropriate treatment in cystic fibrosis (CF). Large copy number variants like duplications the CFTR gene are rare and often classified as of uncertain significance (VUSs) due to unknown characteristics inserted material, complicating decisions. We identified a previously uncharacterized exon 22 duplication (CFTRdup22) two anamnestically unrelated people with CF, both exhibiting mild phenotype. Initial classification VUS was based on standard testing. employed custom next-generation sequencing (NGS) panel determine exact breakpoints conducted mRNA confirm its effect splicing. DNA RNA analyses allowed precise breakpoint determination, confirming that tandem reading frame remained intact. This, well residual CFTRdup22 function ~30% measured via intestinal current measurement, consistent clinically milder CF Collectively, characterization variants’ breakpoints, localization orientation enabled us reclassify variant likely pathogenic. This study highlights importance advanced techniques, such NGS analysis, accurately identifying CF-causing variants. It underscores comprehensive approach persistence when suspecting specific condition. can aid reclassifying VUSs, providing definitive affected family enabling therapeutic interventions, including use modulators.

Language: Английский

Identification and Characterization of a Rare Exon 22 Duplication in CFTR in Two Families DOI Open Access
Simone Ahting,

Constance Henn,

Maike vom Hove

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4487 - 4487

Published: May 8, 2025

Accurate genetic diagnosis is essential for appropriate treatment in cystic fibrosis (CF). Large copy number variants like duplications the CFTR gene are rare and often classified as of uncertain significance (VUSs) due to unknown characteristics inserted material, complicating decisions. We identified a previously uncharacterized exon 22 duplication (CFTRdup22) two anamnestically unrelated people with CF, both exhibiting mild phenotype. Initial classification VUS was based on standard testing. employed custom next-generation sequencing (NGS) panel determine exact breakpoints conducted mRNA confirm its effect splicing. DNA RNA analyses allowed precise breakpoint determination, confirming that tandem reading frame remained intact. This, well residual CFTRdup22 function ~30% measured via intestinal current measurement, consistent clinically milder CF Collectively, characterization variants’ breakpoints, localization orientation enabled us reclassify variant likely pathogenic. This study highlights importance advanced techniques, such NGS analysis, accurately identifying CF-causing variants. It underscores comprehensive approach persistence when suspecting specific condition. can aid reclassifying VUSs, providing definitive affected family enabling therapeutic interventions, including use modulators.

Language: Английский

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