AUTHOR=Lau Sydney A. , Fawaz Romy I. , Rigobello Robert , Bawazeer Shahad , Alajaji Nouf M. , Faqeih Eissa , Li Yanchun , Feng Yanming , Xia Fan , Eng Christine M. , Abedalthagafi Malak 

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

JOURNAL=Frontiers in Medicine

VOLUME=Volume 11 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1390693

DOI=10.3389/fmed.2024.1390693

ISSN=2296-858X

ABSTRACT=Cell-free fetal DNA (cffDNA) screening is a valuable tool in clinical practice for detecting chromosomal abnormalities and autosomal dominant conditions. This study introduces a novel proofof-concept assay designed for autosomal recessive (AR) cffDNA screening, focusing on cases involving the NPC1 gene. Our aim is 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 consented at 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 age of the participants. All were in between 15-18 weeks of gestations. 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 which included in-house built data processing scripts. Importantly, the results were not disclosed to the patients.Our findings showed that in all three cases, AR cffDNA screening results were concordant 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.