Publications about genetic testing for neurological disorders
  1. Dementia gene panel

Dementia panel

May 17, 2018

Disease synonyms

Dementia describes a set of clinical symptoms that include impairment of memory, communication, and ability to perform daily tasks. The lifetime risk of dementia in the general population is 10%. Approximately 25% of all people aged 55 years and older have a positive family history of dementia 1.

According to clinical and research criteria there are four primary dementia subtypes 1, 2:

1) Alzheimer’s disease (most common)

2) Vascular dementias

3) Frontotemporal dementias

4) Dementia with Lewy bodies.

Autosomal dominant

5-10% of adults >60 years of age have dementia3

Major clinical symptoms 4:

  • Memory failure and memory loss, subtle and poorly recognized, progressive.
  • Language disturbance.
  • Confusion and poor judgment.
  • Progressive behavioral changes, agitation, withdrawal, and hallucinations.

Less common clinical symptoms 4:

  • Seizures and myoclonus
  • Parkinsonian features
  • Increased muscle tone
  • Incontinence
  • General malnutrition, pneumonia.
  • Presence of the specific clinical features for progressive dementia.
  • Neuropathologic findings of β-amyloid plaques and intraneuronal neurofibrillary tangles are the gold standard for diagnosis (however, performed only on the brain tissue).
  • Positive family history of dementia.
  • Identification of a heterozygous pathogenic variant in one of the following genes (Table 1): APOE, APP, CHMP2B, CSF1R, FUS, GRN, MAPT, PRNP, PSEN1, PSEN2, SORL1, TARDBP, TREM2, UBE3A, VCP.
  • There are no specific treatments or cures to slow or stop the progression of dementia.
  • There are medications that can reduce agitation and other behavioral problems and/or depression which can improve quality of life4
  • Depression
  • Parkinson disease
  • Amyotrophic lateral sclerosis
  • Picks disease
  • Creutzfeldt-Jakob disease
  • Chronic drug intoxication
  • Chronic CNS infection
  • Thyroid disease
  • Vitamin B12 and thiamine deficiencies 

To confirm/establish the diagnosis, CENTOGENE offers the following tests:

  • Dementia NGS Panel Plus which includes sequencing of the genes APOE, APP, CHMP2B, CSF1R, FUS, GRN, MAPT, PRNP, PSEN1, PSEN2, SORL1, TARDBP, TREM2, UBE3A, VCP and repeat expansion analysis of the genes C9orf72 and PRNP
  • Dementia NGS Panel Plus + CNV which includes sequencing and additionally detection of large deletions and duplications from the NGS data
  • Individuals with a positive family history of dementia
  • Individuals with most common symptoms of dementia (regardless of family history)

Confirmation of a clinical diagnosis through genetic testing of dementia can allow for genetic counseling and may direct medical management.

Table 1: Overview of genes included in Dementia panel

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
APOE 107741 Alzheimer disease-2; Sea-blue histiocyte disease; ?Macular degeneration, age-related; Lipoprotein glomerulopathy; Coronary artery disease, severe, susceptibility to; Hyperlipoproteinemia, type III AD, AR 4
APP 104760 Alzheimer disease 1, familial; Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants AD 38
CHMP2B 609512 Dementia, familial, nonspecific; Amyotrophic lateral sclerosis 17 AD 3
CSF1R 164770 Leukoencephalopathy, diffuse hereditary, with spheroids AD 29
FUS 137070 Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia; Essential tremor, hereditary, 4 AD 26
GRN 138945 Aphasia, primary progressive; Frontotemporal lobar degeneration with ubiquitin-positive inclusions; Ceroid lipofuscinosis, neuronal, 11 AD, AR 18
MAPT 157140 Parkinson disease, susceptibility to; Pick disease; Supranuclear palsy, progressive atypical; Dementia, frontotemporal, with or without parkinsonism; Supranuclear palsy, progressive AD, AR, Isolated cases, MF 25
PRNP 176640 Creutzfeldt-Jakob disease; Cerebral amyloid angiopathy, PRNP-related; Gerstmann-Straussler disease; Kuru, susceptibility to; Insomnia, fatal familial; Huntington disease-like 1; Prion disease with protracted course AD 7
PSEN1 104311 Pick disease; Dementia, frontotemporal; Alzheimer disease, type 3; Alzheimer disease, type 3, with spastic paraparesis and apraxia; Alzheimer disease, type 3, with spastic paraparesis and unusual plaques; Cardiomyopathy, dilated, 1U; ?Acne inversa, familial, 3 AD, Isolated cases 16
PSEN2 600759 Alzheimer disease-4; Cardiomyopathy, dilated, 1V AD 15
SORL1 602005 44
TARDBP 605078 Amyotrophic lateral sclerosis 10, with or without FTD; Frontotemporal lobar degeneration, TARDBP-related AD 11
TREM2 605086 Nasu-Hakola disease AR 3
UBE3A 601623 Angelman syndrome Isolated cases 19
VCP 601023 Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1; Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia; Charcot-Marie-Tooth disease, type 2Y AD 13