Table 3.

Mutations of various types cause neurological disease

Mutation type	Mutation subtype(s)	Example(s)a
Structural variation
Chromosomal abnormalities visible by  conventional karyotype	Aneuploidy	Down syndrome (MIM 190685)
	Translocation	X-linked mental retardation 58 (MIM 300210;  Zemni et al. 2000)
Copy-number variation (CNV)	Genomic deletion	Hereditary neuropathy with liability to pressure  palsies (MIM 162500)
	Genomic duplication	Charcot–Marie–Tooth disease, type 1A (MIM  118220)
	Whole gene deletion	Autosomal recessive early onset Parkinson disease 6  (MIM 605909; PINK1 deletion; Marongiu et al. 2007)
	Whole gene duplication	Early-onset Alzheimer disease with cerebral  amyloid angiopathy (MIM 104300; APP  duplication; Rovelet-Lecrux et al. 2006; Delabar et al. 1987)
	Intragenic Deletion	Duchenne muscular dystrophy (MIM 310200;  deletions in DMD)
	Intragenic duplication	Autosomal dominant dopa-responsive dystonia  (MIM 128230; duplication in GCH1; Ling et al. 2011)
	Non-coding	X-linked spastic paraplegia type 2 (MIM 312920;  duplication 136 kilobases downstream of PLP1;  Lee et al. 2006)
Inversion	–	Duchenne muscular dystrophy (MIM 310200) and  other features (inv(X)(p21.2q22.2); Saito-Ohara et al. 2002)
Microsatellite expansion	Triplet repeat (polyglutamine)	Huntington disease (MIM 143100; expansion in  HTT)
	Triplet repeat (polyalanine)	Congenital central hypoventilation syndrome (MIM  209880; expansion in PHOXB2)
	Triplet repeat (other)	Fragile X mental retardation syndrome (MIM  300624; CGG repeat expansion in FMR1 5′ UTR)
		Myotonic dystrophy 1 (MIM 160900; CTG repeat  expansion in DMPK 3′UTR)
SNV
Insertions/deletions (indels)	Frameshift, splice site, addition or  deletion of amino acid(s)	Many neurological disorders with a genetic basis
Point mutation	Missense, nonsense, frameshift,  splice site	Many neurological disorders with a genetic basis
Epigenetic	–	Prader-Willi syndrome (MIM 176270; maternal  heterodisomy of non-mutated chromosome 15;  Nicholls et al. 1989)
Mutations in small RNAs	–	Autosomal dominant deafness 50 (MIM 613074;  mutations in miR-96; Mencía et al. 2009)

^aJust as multiple diseases may result from a given mutation type, multiple mutation types may cause a given disease (see Fig. 1). SNV simple nucleotide variation