Genetic candidate variants in two multigenerational families with childhood apraxia of speech

Beate Peter, Ellen M. Wijsman, Alejandro Q. Nato, of Washington Center for Mendelian Genomics University of Washington Center for Mendelian Genomics, Mark M. Matsushita, Kathy L. Chapman, Ian B. Stanaway, John Wolff, Kaori Oda, Virginia B. Gabo, Wendy H. Raskind, M. Bamshad, D. Nickerson, J. Shendure

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Childhood apraxia of speech (CAS) is a severe and socially debilitating form of speech sound disorder with suspected genetic involvement, but the genetic etiology is not yet well understood. Very few known or putative causal genes have been identified to date, e.g., FOXP2 and BCL11A. Building a knowledge base of the genetic etiology of CAS will make it possible to identify infants at genetic risk and motivate the development of effective very early intervention programs. We investigated the genetic etiology of CAS in two large multigenerational families with familial CAS. Complementary genomic methods included Markov chain Monte Carlo linkage analysis, copy-number analysis, identity-by-descent sharing, and exome sequencing with variant filtering. No overlaps in regions with positive evidence of linkage between the two families were found. In one family, linkage analysis detected two chromosomal regions of interest, 5p15.1-p14.1, and 17p13.1-q11.1, inherited separately from the two founders. Single-point linkage analysis of selected variants identified CDH18 as a primary gene of interest and additionally, MYO10, NIPBL, GLP2R, NCOR1, FLCN, SMCR8, NEK8, and ANKRD12, possibly with additive effects. Linkage analysis in the second family detected five regions with LOD scores approaching the highest values possible in the family. A gene of interest was C4orf21 (ZGRF1) on 4q25-q28.2. Evidence for previously described causal copy-number variations and validated or suspected genes was not found. Results are consistent with a heterogeneous CAS etiology, as is expected in many neurogenic disorders. Future studies will investigate genome variants in these and other families with CAS.

Original languageEnglish (US)
Article numbere0153864
JournalPLoS One
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2016

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Apraxias
childhood
linkage (genetics)
Genes
etiology
Exome
genes
Markov Chains
Knowledge Bases
additive effect
Markov processes
Genome
Acoustic waves
genomics
genome

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Peter, B., Wijsman, E. M., Nato, A. Q., University of Washington Center for Mendelian Genomics, O. W. C. F. M. G., Matsushita, M. M., Chapman, K. L., ... Shendure, J. (2016). Genetic candidate variants in two multigenerational families with childhood apraxia of speech. PLoS One, 11(4), [e0153864]. https://doi.org/10.1371/journal.pone.0153864

Genetic candidate variants in two multigenerational families with childhood apraxia of speech. / Peter, Beate; Wijsman, Ellen M.; Nato, Alejandro Q.; University of Washington Center for Mendelian Genomics, of Washington Center for Mendelian Genomics; Matsushita, Mark M.; Chapman, Kathy L.; Stanaway, Ian B.; Wolff, John; Oda, Kaori; Gabo, Virginia B.; Raskind, Wendy H.; Bamshad, M.; Nickerson, D.; Shendure, J.

In: PLoS One, Vol. 11, No. 4, e0153864, 01.04.2016.

Research output: Contribution to journalArticle

Peter, B, Wijsman, EM, Nato, AQ, University of Washington Center for Mendelian Genomics, OWCFMG, Matsushita, MM, Chapman, KL, Stanaway, IB, Wolff, J, Oda, K, Gabo, VB, Raskind, WH, Bamshad, M, Nickerson, D & Shendure, J 2016, 'Genetic candidate variants in two multigenerational families with childhood apraxia of speech', PLoS One, vol. 11, no. 4, e0153864. https://doi.org/10.1371/journal.pone.0153864
Peter B, Wijsman EM, Nato AQ, University of Washington Center for Mendelian Genomics OWCFMG, Matsushita MM, Chapman KL et al. Genetic candidate variants in two multigenerational families with childhood apraxia of speech. PLoS One. 2016 Apr 1;11(4). e0153864. https://doi.org/10.1371/journal.pone.0153864
Peter, Beate ; Wijsman, Ellen M. ; Nato, Alejandro Q. ; University of Washington Center for Mendelian Genomics, of Washington Center for Mendelian Genomics ; Matsushita, Mark M. ; Chapman, Kathy L. ; Stanaway, Ian B. ; Wolff, John ; Oda, Kaori ; Gabo, Virginia B. ; Raskind, Wendy H. ; Bamshad, M. ; Nickerson, D. ; Shendure, J. / Genetic candidate variants in two multigenerational families with childhood apraxia of speech. In: PLoS One. 2016 ; Vol. 11, No. 4.
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