PMC10106611_01
TMEM106B gene structure, TMEM106B haplotype-associated phenotypes and family pedigree. (A) Gene architecture and effect of risk/protective haplotype of TMEM106B. The TMEM106B gene is comprised of nine exons, coding regions are labeled in purple. The major SNPs associated with neurodegenerative diseases are indicated with sentinel SNP (rs1990622), located in the regulatory sequence downstream of TMEM106B, and coding variant rs3173615 (c.554C > G, p.Thr185Ser). (B) Current understanding of the effect of TMEM106B haplotype on brain health and disease susceptibility in FTLD-GRN. (C) Family pedigree. Patient II-2 presented in the clinic in their 50s with symptoms of bvFTD. Genetic testing revealed a disease-causing variant in GRN (c.349 + 1G > C, Splice donor). The patient's asymptomatic parent (I-1) and younger sibling (II-1) who also carry the mutation were evaluated in their 80s and late 40s, respectively. TMEM106B genotyping showed I-1 and II-1 to have two copies of the protective TMEM106B allele (SS), while the patient is heterozygous (TS). The children of II-1 and II-2, were not genetically tested but are at risk of carrying the mutation, as represented with a question mark within the symbol. Figure was created using BioRender.com.
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fig1
The patient's family history was unremarkable (Figure 1C).
MRI images of the proband at evaluation. Portrayed are representative images from a T1-weighted sequence indicating severe global atrophy, slightly right > left, most pronounced in frontal, temporal, and parietal regions, and deemed consistent with behavioral variant frontotemporal dementia.
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The clinical impression was behavioral variant frontotemporal dementia (bvFTD), which the neuropsychological testing and neuroimaging workup supported (Table 1; Figure 2).
PMC10106611_02
TMEM106B gene structure, TMEM106B haplotype-associated phenotypes and family pedigree. (A) Gene architecture and effect of risk/protective haplotype of TMEM106B. The TMEM106B gene is comprised of nine exons, coding regions are labeled in purple. The major SNPs associated with neurodegenerative diseases are indicated with sentinel SNP (rs1990622), located in the regulatory sequence downstream of TMEM106B, and coding variant rs3173615 (c.554C > G, p.Thr185Ser). (B) Current understanding of the effect of TMEM106B haplotype on brain health and disease susceptibility in FTLD-GRN. (C) Family pedigree. Patient II-2 presented in the clinic in their 50s with symptoms of bvFTD. Genetic testing revealed a disease-causing variant in GRN (c.349 + 1G > C, Splice donor). The patient's asymptomatic parent (I-1) and younger sibling (II-1) who also carry the mutation were evaluated in their 80s and late 40s, respectively. TMEM106B genotyping showed I-1 and II-1 to have two copies of the protective TMEM106B allele (SS), while the patient is heterozygous (TS). The children of II-1 and II-2, were not genetically tested but are at risk of carrying the mutation, as represented with a question mark within the symbol. Figure was created using BioRender.com.
fneur-14-1160248-g001.jpg
PMC10106611_02_fneur-14-1160248-g001.jpg
fig1
The patient's family history was unremarkable (Figure 1C).
PMC10106611_03