NDLI: Uncertain significance and molecular insights of CPLANE1 variants in prenatal diagnosis of Joubert syndrome: a case report

Content Provider	Springer Nature : BioMed Central
Author	Li, Si-Xiu Chen, Leiting Deng, Chen Tang, Dongmei Zhang, Jing Hu, Wen-Guang Hu, Yu Lai, Hua Yang, Xiao
Abstract	Background Prenatal whole exome sequencing (WES) is becoming an increasingly used diagnostic tool for fetuses with structural anomalies. However, the identification of variants of uncertain significance (VUS) in clinically relevant genes can significantly complicate prenatal diagnosis and genetic counseling. Case presentation A fetus conceived through in vitro fertilization at the third attempt presented with polydactyly and molar tooth sign at 24 + 6 weeks of gestation. Trio-based WES was performed on both parents and the affected fetus, revealing a pair of compound heterozygous CPLANE1 variants (c.4646 A > T/p.Glu1549Val and c.1233 C > A/p.Tyr411) potentially associated with Joubert syndrome. According to the ACMG guidelines, one of the biallelic variants was classified as VUS, and the other as pathogenic. However, these variants had no allele frequencies in the general population. The p.Tyr411 variant was classified as deleterious, while the p.Glu1549Val variant was located in highly conserved residues, was predicted to be damaging by in silico tools, and altered hydrogen bonding. Furthermore, CPLANE1 expression was highest in the brain during the embryonic and fetal stages. These findings provide additional support for the association between CPLANE1 variants in this fetus and Joubert syndrome. Thus, the most likely diagnosis was Joubert syndrome, and after careful consideration, the couple decided to terminate the pregnancy. Conclusion The expression patterns of CPLANE1 and the molecular effects of the variants may provide further evidence supporting the potential for prenatal diagnosis of Joubert syndrome in the case of biallelic VUS and pathogenic variant. This study suggests that molecular insights may play a role in interpreting VUS in clinically relevant prenatal genes for prenatal diagnosis.
Related Links	https://bmcpregnancychildbirth.biomedcentral.com/counter/pdf/10.1186/s12884-024-07052-3.pdf
Ending Page	6
Page Count	6
Starting Page	1
File Format	HTM / HTML
ISSN	14712393
DOI	10.1186/s12884-024-07052-3
Journal	BMC Pregnancy and Childbirth
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2024-12-26
Access Restriction	Open
Subject Keyword	Reproductive Medicine Maternal and Child Health Gynecology CPLANE1 gene Prenatal diagnosis Variants of uncertain significance Molecular effects Gene expression Joubert syndrome
Content Type	Text
Resource Type	Case study
Subject	Obstetrics and Gynecology
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	3.4/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Prenatal diagnosis of Noonan syndrome in a set of monozygotic twins- a case report

Prenatal diagnosis of Neu-Laxova syndrome: a case report

Prenatal diagnosis of 18p deletion and 8p trisomy syndrome: literature review and report of a novel case

Prenatal diagnosis of auriculocondylar syndrome with a novel missense variant of GNAI3: a case report

Prenatal diagnosis of megaduodenum using ultrasound: a case report

Novel variants identified in five Chinese families with Joubert Syndrome: a case report

Prenatal diagnosis of fetal microhydranencephaly: a case report and literature review

Prenatal ultrasound findings of ectodermal dysplasia: a case report

Prenatal diagnosis of Wolf-Hirschhorn syndrome (4p-) in association with congenital hypospadias and foot deformity

Uncertain significance and molecular insights of CPLANE1 variants in prenatal diagnosis of Joubert syndrome: a case report

Similar Documents

Prenatal diagnosis of Noonan syndrome in a set of monozygotic twins- a case report

Prenatal diagnosis of Neu-Laxova syndrome: a case report

Prenatal diagnosis of 18p deletion and 8p trisomy syndrome: literature review and report of a novel case

Prenatal diagnosis of auriculocondylar syndrome with a novel missense variant of GNAI3: a case report

Prenatal diagnosis of megaduodenum using ultrasound: a case report

Novel variants identified in five Chinese families with Joubert Syndrome: a case report

Prenatal diagnosis of fetal microhydranencephaly: a case report and literature review

Prenatal ultrasound findings of ectodermal dysplasia: a case report

Prenatal diagnosis of Wolf-Hirschhorn syndrome (4p-) in association with congenital hypospadias and foot deformity

Uncertain significance and molecular insights of CPLANE1 variants in prenatal diagnosis of Joubert syndrome: a case report