DO: 4428; MONDO: 0011418;
Cytogenetic location: 2p16-p15 Genomic coordinates (GRCh38) : 2:47,500,001-63,900,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 2p16-p15 | {Dyslexia, susceptibility to, 3} | 604254 | 2 |
For a phenotypic description and a discussion of genetic heterogeneity of susceptibility loci for dyslexia, see DYX1 (127700).
Fagerheim et al. (1999) studied 36 members of a Norwegian family in which dyslexia was inherited as an autosomal dominant trait. They initiated a genomewide search for linkage using an average 20-cM marker density. Linkage analysis was performed assuming autosomal dominant inheritance with reduced penetrance. Three different models were used, and lod scores of 3.54, 2.92, and 4.32 were obtained for the region 2p16-p15. GENEHUNTER analysis identified the most likely position of the gene as a 4-cM interval bounded by D2S2352 and D2S1337.
In a study of 96 Canadian families in which at least 2 sibs were diagnosed with phonologic coding dyslexia, Petryshen et al. (2002) provided further evidence for the DYX3 locus. Although 2-point and multipoint parametric linkage analyses provided weak evidence for linkage to the DYX3 region, nonparametric linkage analysis provided the strongest evidence for linkage to DYX3, with a peak lod score of 2.33 at D2S1352. Multipoint variance component linkage analysis of phonologic awareness, phonologic coding, and spelling measures yielded positive scores within the region.
In Finland, Kaminen et al. (2003) performed a genomewide scan in 11 families containing 38 patients with dyslexia. Linkage was observed to 2p11, corresponding to the DYX3 locus.
Peyrard-Janvid et al. (2004) presented mapping evidence suggesting that there may be a second locus for dyslexia, distinct from DYX3, on the short arm of chromosome 2 (specifically, 2p11).
Peter et al. (2014) reported an 11-year-old boy with mild intellectual disability and a severe speech sound disorder associated with a de novo heterozygous 203-kb deletion at 2p16.1 (612513) including only the BCL11A gene (606557). He had some features associated with larger deletions of 2p16-p15, including abnormal muscle tone and delayed motor development, but lacked other significant features, such as craniofacial or skeletal anomalies and optic nerve impairment. His language difficulties were significant and included poor expressive speech, dysarthria in the orofacial region, and childhood apraxia of speech. Peter et al. (2014) suggested a specific role for the BCL11A gene in language development, and noted that this gene falls within the DYX3 locus. The patient also had a 343-kb duplication on 2q13 and an 80-kb duplication on 6p25.3.
Fagerheim, T., Raeymaekers, P., Tonnessen, F. E., Pedersen, M., Tranebjaerg, L., Lubs, H. A. A new gene (DYX3) for dyslexia is located on chromosome 2. J. Med. Genet. 36: 664-669, 1999. [PubMed: 10507721]
Kaminen, N., Hannula-Jouppi, K., Kestila, M., Lahermo, P., Muller, K., Kaaranen, M., Myllyluoma, B., Voutilainen, A., Lyytinen, H., Nopola-Hemmi, J., Kere, J. A genome scan for developmental dyslexia confirms linkage to chromosome 2p11 and suggests a new locus on 7q32. J. Med. Genet. 40: 340-345, 2003. [PubMed: 12746395] [Full Text: https://doi.org/10.1136/jmg.40.5.340]
Peter, B., Matsushita, M., Oda, K., Raskind, W. De novo microdeletion of BCL11A is associated with severe speech sound disorder. Am. J. Med. Genet. 164A: 2091-2096, 2014. [PubMed: 24810580] [Full Text: https://doi.org/10.1002/ajmg.a.36599]
Petryshen, T. L., Kaplan, B. J., Hughes, M. L., Tzenova, J., Field, L. L. Supportive evidence for the DYX3 dyslexia susceptibility gene in Canadian families. J. Med. Genet. 39: 125-126, 2002. [PubMed: 11836362] [Full Text: https://doi.org/10.1136/jmg.39.2.125]
Peyrard-Janvid, M., Anthoni, H., Onkamo, P., Lahermo, P., Zucchelli, M., Kaminen, N., Hannula-Jouppi, K., Nopola-Hemmi, J., Voutilainen, A., Lyytinen, H., Kere, J. Fine mapping of the 2p11 dyslexia locus and exclusion of TACR1 as a candidate gene. Hum. Genet. 114: 510-516, 2004. [PubMed: 15007729] [Full Text: https://doi.org/10.1007/s00439-004-1103-0]