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Volume 15 No. 03
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Accepted Papers

Case Reports

A Novel c.676_677insG PHOX2B Mutation in Congenital Central Hypoventilation Syndrome

Guodong Ye, PhD1,2,3; Daxiong Han, PhD4; Yu Jiang, MS1; Zengge Wang, MS1; Yulin Zhou, PhD1; Xinzhu Lin, BS5; Weiwei Chen, MS2; Maoli Chen, MS2; Jianxiong Xu, MS2; Yanyan Yang, MS6; Qiwei Guo, MS1
1United Diagnostic and Research Center for Clinical Genetics, School of Public Health of Xiamen University and Xiamen Maternal and Child Health Hospital, Xiamen, China; 2Xiamen LifeInt Technology Co., Ltd, Xiamen, China; 3School of Basic Medical Sciences, Jinan University, Guangzhou, China; 4School of Pharmaceutical Sciences, Xiamen University, Xiamen, China; 5Department of Neonatology, Xiamen Maternal and Child Health Hospital, Xiamen, China; 6Third Institute of Oceanography, State Oceanic Administration, Xiamen, China

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.


Ye G, Han D, Jiang Y, Wang Z, Zhou Y, Lin X, Chen W, Chen M, Xu J, Yang Y, Guo Q. A novel c.676_677insG PHOX2B mutation in congenital central hypoventilation syndrome. J Clin Sleep Med. 2019;15(3):509–513.

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