Stuttering

Stuttering is a common speech disorder in which the flow of speech is disrupted by involuntary repetitions and prolongations of sounds, syllables, words or phrases, and involuntary silent pauses or blocks in which the stutterer is unable to produce sounds.Wikipedia

Although the underlying causes of stuttering remain unknown, a variety of studies have concluded that genes play a significant role. Recently (2010), rare mutations in 3 genes have been found, and together, these SNPs may explain ~10% of all cases of stuttering. Interestingly, 2 of the 3 genes were previously known as being implicated in lysosomal storage diseases such as mucolipidosis; in those cases, the inheritance was recessive, whereas in stuttering, all SNPs seen were heterozygous.[PMID 20147709]

The variants implicated in stuttering include the following (listed by gene):

• GNPTAB
  • rs137853825, c.3598G>A, Glu1200Lys; in exon 19, the most common of the stuttering-associated mutations
  • rs137853824, c.961A>G, Ser321Gly; in exon 9
  • rs137853822, c.1363G>T, Ala455Ser; in exon 11
  • rs137853823, c.1875C>G, Phe624Leu; in exon 13

• GNPTG
  • c.11_19dup, Leu 5_ Arg 7dup; in exon 1
  • rs137853826, c.74C>A, Ala25Glu; in exon 2
  • rs137853827, c.688C>G, Leu230Val; in exon 9

• NAGPA
  • c.252C>G, His84Gln; in exon 2
  • rs139526942, c.982C>T, Arg328Cys; in exon 6
  • c.1538_1553del, Phe513SerfsX113; in exon 10

• AP4E1; from [PMID 26544806]
  • rs760021635, c.1549G>A (p.Val517Ile)
  • rs556450190, c.2401G>A (p.Glu801Lys)

Numbering is based on reference sequences NM_024312, NM_032520, and NM_016256, respectively.[PMID 20147709]