IFNAR1 gene mutation may contribute to developmental stuttering in the Chinese population

Abstract Background Developmental stuttering is the most common form of stuttering without apparent neurogenic or psychogenic impairment. Recently, whole-exome sequencing (WES) has been suggested to be a promising approach to study Mendelian disorders. Methods Here, we describe an application of WES...

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Autores principales:	Yimin Sun, Yong Gao, Yuxi Zhou, Yulong Zhou, Ying Zhang, Dong Wang, Li-Hai Tan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	IFNAR1 Developmental stuttering Whole-exome sequencing (WES) Persistent developmental stuttering (PDS) Genetics QH426-470
Acceso en línea:	https://doaj.org/article/e273dcdf35b64e959c8b8b3d205cc06a
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spelling	oai:doaj.org-article:e273dcdf35b64e959c8b8b3d205cc06a2021-11-21T12:07:10ZIFNAR1 gene mutation may contribute to developmental stuttering in the Chinese population10.1186/s41065-021-00211-y1601-5223https://doaj.org/article/e273dcdf35b64e959c8b8b3d205cc06a2021-11-01T00:00:00Zhttps://doi.org/10.1186/s41065-021-00211-yhttps://doaj.org/toc/1601-5223Abstract Background Developmental stuttering is the most common form of stuttering without apparent neurogenic or psychogenic impairment. Recently, whole-exome sequencing (WES) has been suggested to be a promising approach to study Mendelian disorders. Methods Here, we describe an application of WES to identify a gene potentially responsible for persistent developmental stuttering (PDS) by sequencing DNA samples from 10 independent PDS families and 11 sporadic cases. Sanger sequencing was performed for verification with samples obtained from 73 additional patients with sporadic cases. Results We first searched for cosegregating variants/candidate genes in a Chinese family (Family 0) by sequencing DNA obtained from 3 affected members and 3 controls. Next, we sequenced DNA samples obtained from 9 additional Chinese families (Families 1-9) with stuttering to verify the identified candidate genes. Intriguingly, we found that two missense variants (Leu552Pro and Lys428Gln) of interferon-alpha/beta receptor 1 (IFNAR1) cosegregated with stuttering in three independent families (Families 0, 5 and 9). Moreover, we found two additional mutations (Gly301Glu and Pro335del) in the IFNAR1 gene in 4 patients with sporadic cases by using WES or Sanger sequencing. Further receptor mutagenesis and cell signaling studies revealed that these IFNAR1 variants may impair the activity of type I IFN signaling. Conclusion Our data indicate that IFNAR1 might be a potential pathogenic gene of PDS in the Chinese population.Yimin SunYong GaoYuxi ZhouYulong ZhouYing ZhangDong WangLi-Hai TanBMCarticleIFNAR1Developmental stutteringWhole-exome sequencing (WES)Persistent developmental stuttering (PDS)GeneticsQH426-470ENHereditas, Vol 158, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	IFNAR1 Developmental stuttering Whole-exome sequencing (WES) Persistent developmental stuttering (PDS) Genetics QH426-470
spellingShingle	IFNAR1 Developmental stuttering Whole-exome sequencing (WES) Persistent developmental stuttering (PDS) Genetics QH426-470 Yimin Sun Yong Gao Yuxi Zhou Yulong Zhou Ying Zhang Dong Wang Li-Hai Tan IFNAR1 gene mutation may contribute to developmental stuttering in the Chinese population
description	Abstract Background Developmental stuttering is the most common form of stuttering without apparent neurogenic or psychogenic impairment. Recently, whole-exome sequencing (WES) has been suggested to be a promising approach to study Mendelian disorders. Methods Here, we describe an application of WES to identify a gene potentially responsible for persistent developmental stuttering (PDS) by sequencing DNA samples from 10 independent PDS families and 11 sporadic cases. Sanger sequencing was performed for verification with samples obtained from 73 additional patients with sporadic cases. Results We first searched for cosegregating variants/candidate genes in a Chinese family (Family 0) by sequencing DNA obtained from 3 affected members and 3 controls. Next, we sequenced DNA samples obtained from 9 additional Chinese families (Families 1-9) with stuttering to verify the identified candidate genes. Intriguingly, we found that two missense variants (Leu552Pro and Lys428Gln) of interferon-alpha/beta receptor 1 (IFNAR1) cosegregated with stuttering in three independent families (Families 0, 5 and 9). Moreover, we found two additional mutations (Gly301Glu and Pro335del) in the IFNAR1 gene in 4 patients with sporadic cases by using WES or Sanger sequencing. Further receptor mutagenesis and cell signaling studies revealed that these IFNAR1 variants may impair the activity of type I IFN signaling. Conclusion Our data indicate that IFNAR1 might be a potential pathogenic gene of PDS in the Chinese population.
format	article
author	Yimin Sun Yong Gao Yuxi Zhou Yulong Zhou Ying Zhang Dong Wang Li-Hai Tan
author_facet	Yimin Sun Yong Gao Yuxi Zhou Yulong Zhou Ying Zhang Dong Wang Li-Hai Tan
author_sort	Yimin Sun
title	IFNAR1 gene mutation may contribute to developmental stuttering in the Chinese population
title_short	IFNAR1 gene mutation may contribute to developmental stuttering in the Chinese population
title_full	IFNAR1 gene mutation may contribute to developmental stuttering in the Chinese population
title_fullStr	IFNAR1 gene mutation may contribute to developmental stuttering in the Chinese population
title_full_unstemmed	IFNAR1 gene mutation may contribute to developmental stuttering in the Chinese population
title_sort	ifnar1 gene mutation may contribute to developmental stuttering in the chinese population
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e273dcdf35b64e959c8b8b3d205cc06a
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IFNAR1 gene mutation may contribute to developmental stuttering in the Chinese population

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