Article

Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization

1] University of Wisconsin-Madison, Madison, Wisconsin, USA [2] Wisconsin State Laboratory of Hygiene, Madison, Wisconsin, USA.
Genetics in medicine: official journal of the American College of Medical Genetics (Impact Factor: 7.33). 07/2012; 14(11). DOI: 10.1038/gim.2012.72
Source: PubMed

ABSTRACT

Purpose:
The goal of this study was to identify new candidate genes and genomic copy-number variations associated with a rare, severe, and persistent speech disorder termed childhood apraxia of speech. Childhood apraxia of speech is the speech disorder segregating with a mutation in FOXP2 in a multigenerational London pedigree widely studied for its role in the development of speech-language in humans.

Methods:
A total of 24 participants who were suspected to have childhood apraxia of speech were assessed using a comprehensive protocol that samples speech in challenging contexts. All participants met clinical-research criteria for childhood apraxia of speech. Array comparative genomic hybridization analyses were completed using a customized 385K Nimblegen array (Roche Nimblegen, Madison, WI) with increased coverage of genes and regions previously associated with childhood apraxia of speech.

Results:
A total of 16 copy-number variations with potential consequences for speech-language development were detected in 12 or half of the 24 participants. The copy-number variations occurred on 10 chromosomes, 3 of which had two to four candidate regions. Several participants were identified with copy-number variations in two to three regions. In addition, one participant had a heterozygous FOXP2 mutation and a copy-number variation on chromosome 2, and one participant had a 16p11.2 microdeletion and copy-number variations on chromosomes 13 and 14.

Conclusion:
Findings support the likelihood of heterogeneous genomic pathways associated with childhood apraxia of speech.

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Available from: Kathy Jakielski, May 03, 2014
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    • "CNTNAP2 is located downstream from and is regulated by FOXP2 (7q31), which has been linked to the occurrence of CAS in the oft-studied KE family [Lai, Fisher, Hurst, Vargha-Khadem, & Monaco, 2001; Vernes et al., 2008]. CNTNAP2 is closely related to FOXP2 and has been identified as a candidate gene for dyslexia, SLI, and autism [Laffin et al., 2012; Rodenas- Cuadrado, Ho, & Vernes, 2014]. To our knowledge, this is the first report to link variants in CNTNAP2 to CAS without comorbid reading, language, and cognitive impairments, which indicates that CNTNAP2 variants may be associated with deficits in speech production in the absence of comorbid reading, language, and cognitive impairments. "
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    • "A number of distinct etiological mutations affecting this gene have been discovered, in different families and cases (Fisher and Scharff, 2009). These range from missense mutations (Lai et al., 2001; Laffin et al., 2012), non-sense mutations (MacDermot et al., 2005) and indels (Turner et al., 2013), to gross chromosomal abnormalities like translocations (Shriberg et al., 2006; Kosho et al., 2008) and deletions (Zeesman et al., 2006; Palka et al., 2012; Rice et al., 2012; Zilina et al., 2012). The most thoroughly studied FOXP2 disruption is a heterozygous missense mutation that co-segregates with speech and language disorder in 15 members of a three generation pedigree , known as the KE family (Fisher et al., 1998). "
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