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A Novel c.676_677insG PHOX2B Mutation in Congenital Central Hypoventilation Syndrome.
J Clin Sleep Med. 2019 03 15; 15(3):509-513.JC

Abstract

ABSTRACT

Paired-like homeobox (PHOX)2B is considered to be the causative gene of congenital central hypoventilation syndrome (CCHS), a dominant genetic disorder that results in abnormal central respiratory control with resulting hypoventilation during sleep. In this study, we report a novel c.676_677insG (p.Ala226fs) mutation in a patient with severe CCHS, and we evaluated the function of this mutation. The mutation reduced the translation of the mutant PHOX2B protein and impaired its ability to activate the PHOX2A promoter, due to a haploinsufficiency effect. The mutant PHOX2B was able to interact with wildtype PHOX2B, resulting in retention of PHOX2B on the nuclear membrane, which may impair the normal function of the nuclear membrane, and leading to cellular morbidity. Our study provides useful information for the functional studies of PHOX2B and understanding the pathogenesis of CCHS, and thus is beneficial for the prognosis of, genetic counseling for, and development of pharmaceuticals for PHOX2B-associated diseases.

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Authors+Show Affiliations

Ye G
United Diagnostic and Research Center for Clinical Genetics, School of Public Health of Xiamen University and Xiamen Maternal and Child Health Hospital, Xiamen, China. Xiamen LifeInt Technology Co., Ltd, Xiamen, China. School of Basic Medical Sciences, Jinan University, Guangzhou, China.
Han D
School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.
Jiang Y
United Diagnostic and Research Center for Clinical Genetics, School of Public Health of Xiamen University and Xiamen Maternal and Child Health Hospital, Xiamen, China.
Wang Z
United Diagnostic and Research Center for Clinical Genetics, School of Public Health of Xiamen University and Xiamen Maternal and Child Health Hospital, Xiamen, China.
Zhou Y
United Diagnostic and Research Center for Clinical Genetics, School of Public Health of Xiamen University and Xiamen Maternal and Child Health Hospital, Xiamen, China.
Lin X
Department of Neonatology, Xiamen Maternal and Child Health Hospital, Xiamen, China.
Chen W
Xiamen LifeInt Technology Co., Ltd, Xiamen, China.
Chen M
Xiamen LifeInt Technology Co., Ltd, Xiamen, China.
Xu J
Xiamen LifeInt Technology Co., Ltd, Xiamen, China.
Yang Y
Third Institute of Oceanography, State Oceanic Administration, Xiamen, China.
Guo Q
United Diagnostic and Research Center for Clinical Genetics, School of Public Health of Xiamen University and Xiamen Maternal and Child Health Hospital, Xiamen, China.

MeSH

Fatal OutcomeFrameshift MutationHomeodomain ProteinsHumansHypoventilationInfant, NewbornMalePromoter Regions, GeneticSleep Apnea, CentralTranscription Factors

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30853048

Citation

Ye, Guodong, et al. "A Novel c.676_677insG PHOX2B Mutation in Congenital Central Hypoventilation Syndrome." Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine, vol. 15, no. 3, 2019, pp. 509-513.
Ye G, Han D, Jiang Y, et al. A Novel c.676_677insG PHOX2B Mutation in Congenital Central Hypoventilation Syndrome. J Clin Sleep Med. 2019;15(3):509-513.
Ye, G., Han, D., Jiang, Y., Wang, Z., Zhou, Y., Lin, X., Chen, W., Chen, M., Xu, J., Yang, Y., & Guo, Q. (2019). A Novel c.676_677insG PHOX2B Mutation in Congenital Central Hypoventilation Syndrome. Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine, 15(3), 509-513. https://doi.org/10.5664/jcsm.7688
Ye G, et al. A Novel c.676_677insG PHOX2B Mutation in Congenital Central Hypoventilation Syndrome. J Clin Sleep Med. 2019 03 15;15(3):509-513. PubMed PMID: 30853048.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Novel c.676_677insG PHOX2B Mutation in Congenital Central Hypoventilation Syndrome. AU - Ye,Guodong, AU - Han,Daxiong, AU - Jiang,Yu, AU - Wang,Zengge, AU - Zhou,Yulin, AU - Lin,Xinzhu, AU - Chen,Weiwei, AU - Chen,Maoli, AU - Xu,Jianxiong, AU - Yang,Yanyan, AU - Guo,Qiwei, Y1 - 2019/03/15/ PY - 2018/07/31/received PY - 2019/01/07/accepted PY - 2019/3/12/pubmed PY - 2020/7/24/medline PY - 2019/3/12/entrez KW - PHOX2B KW - congenital central hypoventilation syndrome KW - dominant negative effect KW - haploinsufficiency effect KW - nonpolyalanine repeat mutations SP - 509 EP - 513 JF - Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine JO - J Clin Sleep Med VL - 15 IS - 3 N2 - ABSTRACT: Paired-like homeobox (PHOX)2B is considered to be the causative gene of congenital central hypoventilation syndrome (CCHS), a dominant genetic disorder that results in abnormal central respiratory control with resulting hypoventilation during sleep. In this study, we report a novel c.676_677insG (p.Ala226fs) mutation in a patient with severe CCHS, and we evaluated the function of this mutation. The mutation reduced the translation of the mutant PHOX2B protein and impaired its ability to activate the PHOX2A promoter, due to a haploinsufficiency effect. The mutant PHOX2B was able to interact with wildtype PHOX2B, resulting in retention of PHOX2B on the nuclear membrane, which may impair the normal function of the nuclear membrane, and leading to cellular morbidity. Our study provides useful information for the functional studies of PHOX2B and understanding the pathogenesis of CCHS, and thus is beneficial for the prognosis of, genetic counseling for, and development of pharmaceuticals for PHOX2B-associated diseases. SN - 1550-9397 UR - https://www.unboundmedicine.com/medline/citation/30853048/A_Novel_c_676_677insG_PHOX2B_Mutation_in_Congenital_Central_Hypoventilation_Syndrome_ L2 - https://doi.org/10.5664/jcsm.7688 DB - PRIME DP - Unbound Medicine ER -