Intrafamilial phenotypic heterogeneity in a Taiwanese family with a MAPT p.R5H mutation: A case report and literature review
Journal
BMC Neurology
Journal Volume
17
Journal Issue
1
Date Issued
2017
Author(s)
Abstract
Background: Frontotemporal degeneration (FTD) is a clinically and genetically heterogeneous neurodegenerative disorder characterized by deficits in executive function that frequently overlaps with parkinsonism and motor neuron disorders. Several genes have been identified to cause autosomal dominant forms of FTD, including the gene coding for the protein associated with microtubule tau (MAPT). While most reported pathogenic mutations in MAPT occur in exons 9-13, few families have been reported with mutations outside of this region. Herein, we report a first Taiwanese family having the exon 1 p.Arg5His mutation in MAPT with intrafamilial phenotype heterogeneity. Case presentation: A 63-year-old man presented with progressive non-fluent speech and impaired memory for 3 years. He then developed apraxia, myoclonus and parkinsonism feature at his right hand. Extensive neurologic and neurocognitive examination lead to a diagnosis of FTD mixed with corticobasal syndrome. Magnetic resonance imaging revealed asymmetric atrophy in the left frontal and temporal lobes and single-photon emission computed tomography indicated decreased metabolism in the same areas as well as the left basal ganglia. The patient's mother had been diagnosed with amyotrophic lateral sclerosis (ALS) at the age of 60 and was deceased 10 years later due to respiratory failure. The patient's younger sister had persistent depressive disorder in her early forties and did not have any prominent cognitive or motor dysfunctions. We performed genetic analysis applying a targeted next generation sequencing (NGS) panel covering MAPT, GRN, VCP, FUS, CHMP2B, and TARDBP on the proband, followed by Sanger sequencing of candidate genes in eight family members. Hexanucleotide repeat expansion of C9Orf72 was determined by repeat-primed PCR. We identified a missense mutation in exon 1 of MAPT gene, c.14G > A (p.R5H), which was previously reported in only two Japanese patients in a literature review. This substitution co-segregated with the disease phenotypes in the family. Conclusions: This is the first report of the occurrence of the MAPT p.R5H mutation in the Taiwanese population. Our findings extend the current knowledge of phenotypic heterogeneity among family members carrying the MAPT p.R5H mutation. ? 2017 The Author(s).
SDGs
Other Subjects
donepezil; MAPT protein, human; tau protein; adult; amyotrophic lateral sclerosis; aphasia; apraxia; Article; attention disturbance; brain cortex atrophy; C9Orf72 gene; case report; CHMP2B gene; clinical article; corticobasal degeneration; depression; family history; frontotemporal dementia; FUS gene; gene; gene mutation; genetic analysis; genetic analyzer; genetic heterogeneity; GRN gene; human; hyperlipidemia; hypertension; male; MAPT gene; memory disorder; mental disease; middle aged; myoclonus; neurologic examination; next generation sequencing; nuclear magnetic resonance imaging; parkinsonism; phenotype; polymerase chain reaction; prescription; respiratory failure; right handedness; Sanger sequencing; single photon emission computed tomography; speech disorder; stuttering; Taiwanese; TARDBP gene; VCP gene; amyotrophic lateral sclerosis; Asian continental ancestry group; atrophy; frontotemporal dementia; genetics; high throughput sequencing; motor neuron disease; mutation; parkinsonism; pathology; temporal lobe; Amyotrophic Lateral Sclerosis; Asian Continental Ancestry Group; Atrophy; Frontotemporal Dementia; High-Throughput Nucleotide Sequencing; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Motor Neuron Disease; Mutation; Parkinsonian Disorders; tau Proteins; Temporal Lobe; Tomography, Emission-Computed, Single-Photon
Publisher
BioMed Central Ltd.
Type
journal article