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Abstract：
BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disease that is mainly caused by PHOX2B mutations. The purpose of this study is to analyze and summarize the clinical and genetic characteristics of CCHS patients in the Chinese population from our study and previous literature.
METHODS: The potential pathogenic gene mutations of CCHS were identified and verified by next generation sequencing combined with Sanger sequencing, fluorescent probe PCR and capillary electrophoresis. The clinical characteristics and gene mutations of CCHS cases in Chinese population were summarized from our study and previous literature to explore the genotype-phenotype correlations.
RESULTS: We identified 48 CCHS cases including three new cases from our report in China. Overall, 77.1% of the patients had PHOX2B polyalanine repeat expansion mutations (PARMs), and the remaining 22.9% had 10 distinct PHOX2B non-polyalanine repeat expansion mutations (NPARMs). Compared to those with PARMs, patients with NPARMs were more likely to have premature birth (54.5% vs. 2.8%, p < 0.001) and lower birth weight (33.3% vs. 3.2%, p = 0.030), with statistical significance. The patients with PARMs were more likely to have cardiovascular defects (64.9% vs. 27.3%, p = 0.063), cerebral hemorrhage (29.7% vs. 9.1%, p = 0.322) and seizures (37.8% vs. 9.1%, p = 0.151) than those with NPARMs, with no statistical significance.
CONCLUSIONS: CCHS patients with PHOX2B NPARMs were more likely to have premature birth and low birth weight, while PHOX2B PARMs tended to be positively associated with the risk of cardiovascular defects, cerebral hemorrhage and seizures in Chinese population.
METHODS: The potential pathogenic gene mutations of CCHS were identified and verified by next generation sequencing combined with Sanger sequencing, fluorescent probe PCR and capillary electrophoresis. The clinical characteristics and gene mutations of CCHS cases in Chinese population were summarized from our study and previous literature to explore the genotype-phenotype correlations.
RESULTS: We identified 48 CCHS cases including three new cases from our report in China. Overall, 77.1% of the patients had PHOX2B polyalanine repeat expansion mutations (PARMs), and the remaining 22.9% had 10 distinct PHOX2B non-polyalanine repeat expansion mutations (NPARMs). Compared to those with PARMs, patients with NPARMs were more likely to have premature birth (54.5% vs. 2.8%, p < 0.001) and lower birth weight (33.3% vs. 3.2%, p = 0.030), with statistical significance. The patients with PARMs were more likely to have cardiovascular defects (64.9% vs. 27.3%, p = 0.063), cerebral hemorrhage (29.7% vs. 9.1%, p = 0.322) and seizures (37.8% vs. 9.1%, p = 0.151) than those with NPARMs, with no statistical significance.
CONCLUSIONS: CCHS patients with PHOX2B NPARMs were more likely to have premature birth and low birth weight, while PHOX2B PARMs tended to be positively associated with the risk of cardiovascular defects, cerebral hemorrhage and seizures in Chinese population.
摘要：
背景：先天性中枢性通气不足综合征（CCHS）是一种罕见的常染色体显性疾病，主要由PHOX2B突变引起。本研究的目的是从我们的研究和以往的文献中分析和总结中国人群中CCHS患者的临床和遗传特征。
方法：通过下一代测序结合Sanger测序鉴定并验证CCHS的潜在致病基因突变。荧光探针PCR和毛细管电泳。从我们的研究和以前的文献中总结了中国人群中CCHS病例的临床特征和基因突变，以探讨基因型与表型的相关性。
结果：我们在中国的报告中发现了48例CCHS病例，包括3例新病例。总的来说,77.1%的患者有PHOX2B多丙氨酸重复扩增突变(PARMs),其余22.9%有10个明显的PHOX2B非多聚丙氨酸重复扩增突变(NPARMs).与PARM相比，NPARMs患者更容易早产(54.5%vs.2.8%，p<0.001)和较低的出生体重(33.3%vs.3.2%,p=0.030),具有统计学意义。PARMs患者更有可能有心血管缺陷(64.9%vs.27.3%,p=0.063),脑出血（29.7%vs.9.1%，p=0.322）和癫痫发作（37.8%与9.1%，p=0.151)比具有NPARM的那些，没有统计学意义。
结论：患有PHOX2BNPARMs的CCHS患者更有可能早产和低出生体重，虽然PHOX2BPARMs倾向于与心血管缺陷的风险呈正相关，中国人群的脑出血和癫痫发作。
方法：通过下一代测序结合Sanger测序鉴定并验证CCHS的潜在致病基因突变。荧光探针PCR和毛细管电泳。从我们的研究和以前的文献中总结了中国人群中CCHS病例的临床特征和基因突变，以探讨基因型与表型的相关性。
结果：我们在中国的报告中发现了48例CCHS病例，包括3例新病例。总的来说,77.1%的患者有PHOX2B多丙氨酸重复扩增突变(PARMs),其余22.9%有10个明显的PHOX2B非多聚丙氨酸重复扩增突变(NPARMs).与PARM相比，NPARMs患者更容易早产(54.5%vs.2.8%，p<0.001)和较低的出生体重(33.3%vs.3.2%,p=0.030),具有统计学意义。PARMs患者更有可能有心血管缺陷(64.9%vs.27.3%,p=0.063),脑出血（29.7%vs.9.1%，p=0.322）和癫痫发作（37.8%与9.1%，p=0.151)比具有NPARM的那些，没有统计学意义。
结论：患有PHOX2BNPARMs的CCHS患者更有可能早产和低出生体重，虽然PHOX2BPARMs倾向于与心血管缺陷的风险呈正相关，中国人群的脑出血和癫痫发作。
