Intracerebral calcification disorders

Gene: JAM2

Green List (high evidence)

PMID: 31851307 Cen et al., 2020
Reported 3 unrelated families with primary familial brain calcification. Probands harboured biallelic JAM2 variants: homozygous c.140delT, p.L48Ter; homozygous c.1A>G, p.M1? and compound heterozygous mutations [c.504G>C, p.W168C & c.(67+1_68-1)_(394+1_395-1), p.Y23_V131delinsL]. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and asymptomatic at the time of report (1 patient at age 37 years); disease onset ages: 20-38 years. 4/4 patients presented with severe calcifications in the cortex in addition to extensive calcifications in multiple brain areas.

PMID: 32142645 Schottlaender et al., 2023
Report of 7 individuals from 4 families with primary familial brain calcification. Detected biallelic JAM2 variants: homozygous c.685C>T, p.Arg229Ter (2 families); comp het c.395−1dupG, c.323G>A & IVS4-1dupG, p.Arg108His; homozygous c.177_180delCAGA, p.Arg60Ter.
Age of onset: childhood (3/7), teenage (2/7), 20s-30s (2/7).
Phenotype: cerebellar syndrome (6/7), Parkinsonism (5/7), dystonia (3/7), cognitive decline (5/6 assessed), brain calcification (7/7).

Functional evidence: JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient’s fibroblasts; human phenotype of brain calcification is replicated in the jam2 complete knockout mouse (jam2 KO).

JAM2 is associated with Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824 (OMIM accesed 16th Mar 2026).

Created: 16 Mar 2026, 2:53 p.m. | Last Modified: 16 Mar 2026, 2:53 p.m.

Panel Version: 1.37

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824

Publications

• 31851307
• 32142645

Green List (high evidence)

Three unrelated families with bi-allelic variants reported. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and probable asymptomatic (1/4), with diverse onset ages.
Sources: Literature

Created: 20 Apr 2020, 2:49 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Primary brain calcification

Publications

• 31851307

Variants in this GENE are reported as part of current diagnostic practice