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CffDNA screening for Niemann–pick disease, type C1: a case series

Authors :
Sydney A. Lau
Romy I. Fawaz
Robert Rigobello
Shahad Bawazeer
Nouf M. Alajaji
Eissa Faqeih
Yanchun Li
Yanming Feng
Fan Xia
Christine M. Eng
Malak Abedalthagafi
Source :
Frontiers in Medicine, Vol 11 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

Cell-free fetal DNA (cffDNA) screening is a valuable tool in clinical practice for detecting chromosomal abnormalities and autosomal dominant (AD) conditions. This study introduces a novel proof-of-concept assay designed for autosomal recessive (AR) cffDNA screening, focusing on cases involving the NPC1 gene. We aim to illustrate the significant benefits of AR cffDNA screening in managing high-risk pregnancies, specifically where biallelic pathogenic variants in NPC1 cause Niemann–Pick disease, type C1 (NPC), a disorder marked by progressive neurodegeneration. Three participants for this study were recruited and gave consent to a hospital in Saudi Arabia. These participants were either carriers of NPC or had a first- or second-degree relative affected by the disorder. No specific criteria were set for the age of the participants. All were between 15 and 18 weeks of gestation. Using amplicon-based next-generation sequencing (NGS), we analyzed the zygosity and variants in cffDNA extracted from maternal peripheral blood. After amplicon NGS, analysis was completed by a custom data analysis pipeline that included in-house-built data processing scripts and commonly used software packages. Importantly, the results were not disclosed to the patients. Our findings showed that in all three cases, AR cffDNA screening results were consistent with standard invasive diagnostic testing. This screening method offers several advantages: it provides critical information to families earlier in the pregnancy compared to invasive diagnostic tests, and it helps to alleviate parental anxiety. Moreover, this non-invasive method can determine pregnancy status in the first trimester for known familial variants. Future research may extend this approach to screen for known disease-causing variants in common AR conditions.

Details

Language :
English
ISSN :
2296858X
Volume :
11
Database :
Directory of Open Access Journals
Journal :
Frontiers in Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.913f08a699d745fba7a63950cd92ee46
Document Type :
article
Full Text :
https://doi.org/10.3389/fmed.2024.1390693