[Clinical characterization and genetic analysis of a patient with Fahr disease due to a homozygous variant of JAM2 gene].

Authors

Qian Ma, Wenjun Shao, Yiwei Wang, Zheyu Hu, Fengxun Liu

Published in

Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. Volume 43. Issue 9. Pages 708-714. Sep 10, 2026.

Abstract

To explore the clinical presentation and molecular etiology for a patient with Fahr disease due to a variant of JAM2 gene.
A male patient who had presented at the Department of Neurology of the First Affiliated Hospital of Zhengzhou University in January 2021 for unsteady gait for over six months was selected as study subject. Clinical data including medical history, family history, physical examination, routine tests such as blood, urine, and stool examinations for the proband were collected. Cranial CT and MRI were carried out. Peripheral blood samples from the patient and his parents were collected. Following extraction of genomic DNA, whole exome sequence (WES) was carried out. Candidate variant was verified by Sanger sequencing of the family members. Pathogenicity of variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Swiss-Model was used to analyzed the impact of variant on the protein product. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: KS-2018-KY-36).
The patient had developed unsteady gait 6 months before without clear cause, manifesting as a feeling of heaviness in the head and lightness in the feet, a sensation of walking on cotton wool when standing or walking, without facial drooping, blurred vision, numbness or weakness in the limbs, hand tremors, or slow movement. Cranial CT revealed multiple high-density calcifications in the bilateral cerebellar hemispheres, basal ganglia, thalamus, and gray-white matter junction of the cerebral hemispheres. MRI plain scan showed left frontal lobe lateral ventricular infarction, bilateral paraventricular white matter demyelination, bilateral maxillary sinusitis, and right maxillary sinus cyst. No other family members had similar clinical symptoms. WES and Sanger sequencing results showed that the patient has harbored homozygous c.460C>T (p.Arg154*) variant of the JAM2 gene, for which both of his parents were heterozygous carriers. Based on the guidelines from ACMG, the c.460C>T (p.Arg154*) variant was predicted as likely pathogenic (PVS1+PM2_Moderate+PP3+PP4). The variant was unreported previously, and Swiss-Model analysis suggests that it can significantly affect the tertiary structure of JAM2 protein.
The homozygous c.460C>T (p.Arg154*) variant of the JAM2 gene probably underlay the pathogenesis in this pedigree, and the detection of the novel variant has enriched the mutational spectrum of the JAM2 gene.

PMID:
42663027
Bibliographic data and abstract were imported from PubMed on 28 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.