Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Progressive Nonfluent Aphasia
Position: (GRCh38/hg38):Chr6:41159791 G>A
Position: (GRCh37/hg19):Chr6:41127529 G>A
dbSNP ID: NA
Coding/Non-Coding: Non-Coding
DNA Change: Substitution
Expected RNA Consequence: Splicing Alteration
Genomic Region: Intron 3

Findings

This variant substitutes an adenine for a guanine in the splice-donor consensus site at the first position of intron 3 (c.482+1G>A). The variant, in a homozygous state, was found in a 39-year-old Malaysian woman presenting with progressive non-fluent aphasia, apathy, and dementia (Chee, et al., 2017). MRI revealed periventricular white-matter hyperintensities, enlargement of the lateral ventricles, and thinning of the corpus callosum—MRI findings like those seen in Nasu-Hakola disease (NHD). However, no bone involvement, a defining feature of NHD, was seen on X-ray. The patient’s mother and two elder siblings had died at 40–50 years of age, after displaying similar symptoms. A brother also began showing symptoms in his mid-30s.

Neuropathology

Neuropathological characterization is currently lacking. However, MRI showed periventricular white-matter hyperintensities, enlargement of the lateral ventricles, and thinning of the corpus callosum.

Biological Effect

Unknown.

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Paper Citations

1. Chee KY, Gaillard F, Velakoulis D, Ang CL, Chin LK, Ariffin R. A case of TREM2 mutation presenting with features of progressive non-fluent aphasia and without bone involvement. Aust N Z J Psychiatry. 2017 Nov;51(11):1157-1158. Epub 2017 May 2 PubMed.

Further Reading

No Available Further Reading