Genetic Candidate Variants in Two Multigenerational Families with Childhood Apraxia of Speech
| العنوان: | Genetic Candidate Variants in Two Multigenerational Families with Childhood Apraxia of Speech |
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| المؤلفون: | Wendy H. Raskind, Mark Matsushita, Kaori Oda, John Wolff, Ian B. Stanaway, Kathy Chapman, Beate Peter, Ellen M. Wijsman, Virginia B. Gabo, Alejandro Q. Nato |
| المصدر: | PLoS ONE, Vol 11, Iss 4, p e0153864 (2016) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Heredity, Speech-Language Pathology, Etiology, Genetic Linkage, Social Sciences, lcsh:Medicine, Pathology and Laboratory Medicine, Laryngology, 0302 clinical medicine, Medicine and Health Sciences, Psychology, Exome, lcsh:Science, Exome sequencing, Language, Genetics, Multidisciplinary, FOXP2, Pedigree, Genetic Mapping, Childhood apraxia of speech, Linkage Analysis, Medical genetics, Female, Research Article, Risk, medicine.medical_specialty, DNA Copy Number Variations, Genotype, Apraxias, Variant Genotypes, Speech Therapy, Biology, 03 medical and health sciences, Genetic linkage, medicine, Speech, Humans, Genetic Predisposition to Disease, Clinical Genetics, Linkage (software), lcsh:R, Cognitive Psychology, Biology and Life Sciences, Linguistics, Human Genetics, NIPBL, medicine.disease, Human genetics, 030104 developmental biology, Otorhinolaryngology, Cognitive Science, lcsh:Q, Lod Score, 030217 neurology & neurosurgery, Neuroscience |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dcc05db63c2cd7ed881bbb57128d890eTest http://europepmc.org/articles/PMC4847873?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dcc05db63c2cd7ed881bbb57128d890e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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