Table 1 Spectrum of somatic mosaicism detected in neural cells of the diseased brain

Alzheimer’s disease

Single nucleotide variants

Low-level mosaic single nucleotide variants

1

1q42.13

PS2

[53]

14

14q24.2

PS1

17

17q21.31

MAPT

21

21q21.3

APP

Single nucleotide variants

Brain-specific single nucleotide variants

2

2q32.2

COL3A1

[61]

4

4q31.3

LRBA

Single gene mutations

Single gene autosomal dominant variants

11

11q24.1

SORL1

[53]

Single nucleotide variants

Single nucleotide variants in the temporal cortex

1

1q32.2

CD55

[62]

Single nucleotide variants

Pathogenic somatic mutation leading to a loss-of-function mutation

19

19p13.2

PIN1

[63]

Single gene mutations

Accumulating of mosaic somatic mutations in autism/intellectual disability genes

20

20q13.13

ADNP

[64]

Nucleotide repeat expansion

Hexanucleotide repeat expansions

9

9p21.2

C9orf72

[65]

CNVs

CNVs affecting ~ 10% of cells

NS*

NS

NS

[52]

CNV (gain)

Single gene amplification

21

21q21.3

APP

[66]

CNV (gain)

Single gene gain

12

12q13.12

PRPH

[65]

DNA content variation

Increased rates of DNA content variation (variations of DNA content in a cell suggested to hallmark aneuploidy/polyploidy)

—

—

—

[47, 67]

Aneuploidy

Increased rates of aneuploidy

17

—

—

[45, 67]

Aneuploidy (trisomy/monosomy)

Chromosome-specific (numerical) instability

21

Whole chromosome

—

[15]

Aneuploidy (monosomy)

X chromosome loss

(an aging marker)

X

Whole chromosome

—

[46]

Aneuploidy (chromosome instability)

Chromosome missegregation and aneuploidy probably resulted from mutations in the APP, presenelin 1 and, probably, NPC1

21

—

—

reviewed by

[26]

Amyotrophic lateral sclerosis (sporadic)

CNVs

Brain-specific CNVs

3

3p26.3p26.2

CNTN4

[68]

8

8p23.2

CSMD1

22

22q11.22

GGTLC2

Ataxia telangiectasia (ATM mutations)

LINE-1 retrotransposition

Specific LINE-1 retrotransposition

—

—

—

[69]

Aneuploidy (chromosome instability) and chromosome 14-specific instability

(affecting exclusively this chromosome)

High rates of chromosome instability in degenerating areas of the brain suggested to have ATM mutations (aneuploidy, non-random chromosomal breaks, rearranged chromosomes)

1, 7, 11, 13, 14, 17, 18, 21, X, Y

Whole chromosomes

—

[15, 44]

14

14q12

NOVA1, FOXG1B

Autism spectrum disorder

Single gene mutations

Recurrent deleterious mutations

2

2q24.3

SCN1A

[35]

2

2q24.3

SCN2A

3

3p21.31

SETD2

6

6q25.3

ARID1B

LINE-1 retrotransposition

LINE-1 overexpression in the cerebellum

—

—

—

[70]

Focal Cortical Dysplasia

Single nucleotide variants

Missense mutations

9

9q34.13

TSC1

[71, 72]

16

16p13.3

TSC2

1

1p36.22

MTOR

[73]

22

22q12.2q12.3

DEPDC5

[74]

Focal cortical dysplasia, type II

Single nucleotide variants

Somatic doublet mutation

7

7q36.1

RHEB

[75]

Hemimegalen-cephaly

Single nucleotide variants

Missense mutations

1

1q43q44

AKT3

[71, 76]

3

3q26.32

PIK3CA

14

14q32.33

AKT1

Single nucleotide variants

Missense mutations

1

1p36.22

MTOR

[73]

Single nucleotide variants

“Double-hit” single nucleotide variants of two genes

1

1p36.22

MTOR

[77]

9

9p22.1

RPS6

Hypothalamic Hamartoma

Single nucleotide variants

Missense mutations

7

7p14.1

GLI3

[78, 79]

X

Xp22.2

OFD1

Frontotemporal lobar degeneration

Aneuploidy (trisomy)

Neuronal aneuploidy + apoptosis due to mitotic defects caused by MAPT mutations

12, 21

—

—

[80]

Huntington’s disease

Nucleotide repeat expansion

Expansion of an unstable trinucleotide repeat (CAG)

4

4p16.3

HTT

[81]

Lewy body diseases

Aneuploidy (NS)

Increase in neuronal DNA content (probably aneuploidy)

—

—

—

[82]

Niemann-Pick disease, type C1

(NPC1 mutations)

Aneuploidy (trisomy)

Accumulation of (trisomic) cells with additional chromosome 21 in Niemann-Pick disease, type C1

21

—

—

[83]

Nonlesional focal epilepsy

Single gene mutations

Missense mutations, deletions (frameshift), insertions

X

Xp11.23

SLC35A2

[84]

Parkinson’s disease

Single nucleotide variants

Questionable SNCA variants

4

4q22.1

SNCA

[85]

CNV (gains)

Somatic SNCA gains in nigral dopaminergic neurons

4

4q22.1

SNCA

[86]

Rett syndrome (MECP2 mutations)

LINE-1 retrotransposition

Specific LINE-1 retrotransposition

—

—

—

[87]

Schizophrenia

Single nucleotide variants

NS

NS

NS

NS

[88]

CNV (loss)

Somatic deletions

2

2q31.2

PRKRA

[42]

5

5q35.2

BOD1

7

7p15.2

CBX3

CNVs (gains/losses)

Diseases-specific CNVs

4

4q35.2

NS

[43]

6

6p11.2

7

7q11q12

11

11p15.4p15.5

15

15q11.2

LINE-1 retrotransposition

Increased LINE-1 “burden” and LINE-1 insertions in synapse or schizophrenia-related genes

—

—

—

[89, 90]

Aneuploidy (trisomy)

Low-level mosaic trisomy

18, X

—

—

[3]

Aneuploidy (trisomy/monosomy)

Low-level mosaic trisomy and monosomy

1

Whole chromosome

—

[40]

Aneuploidy (trisomy/monosomy)

Increased rates of gonosomal aneuploidy

X, Y

—

—

[41]

Sturge-Weber syndrome (leptomeningeal

angiomatosis)

Single nucleotide variants

Missense mutation (R183Q)

9

9q21.2

GNAQ

[91]

Subcortical band heterotopia (“double cortex” syndrome)

Single gene mutations

Mosaic gene mutations associated with the syndrome

17

17p13.3

PAFAH1B1

(LIS1)

[92, 93]

X

Xq23

DCX

Tuberous Sclerosis

Single nucleotide variants

Missense mutations

16

16p13.3

TSC2

[94]