Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis

doi:10.1007/s11684-017-0567-y

Front. Med.

2018, Vol. 12

Issue (5) : 550-558 https://doi.org/10.1007/s11684-017-0567-y

RESEARCH ARTICLE

Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis

Liru Qiu, Fengjie Yang, Yonghua He, Huiqing Yuan, Jianhua Zhou(

)

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China

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Abstract

Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G>C and c.3062C>T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.

Keywords cystic fibrosis pseudo-Bartter syndrome hypokalemic alkalosis CFTR gene mutations infants diagnosis

Corresponding Author(s): Jianhua Zhou

Just Accepted Date: 25 December 2017 Online First Date: 08 March 2018 Issue Date: 29 September 2018

Cite this article:

Liru Qiu,Fengjie Yang,Yonghua He, et al. Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis[J]. Front. Med., 2018, 12(5): 550-558.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0567-y
https://academic.hep.com.cn/fmd/EN/Y2018/V12/I5/550

Tab.1 Main symptoms of the infants with CF

Tab.2 CFTR gene mutations identified in the three infants with Bartter-syndrome-like symptoms

Fig.1 Sanger sequencing of the CFTR gene from P-1 and parents. c.1040G>A, c.4056G>C, and c.1526G>C compound heterozygous missense mutations were detected. (A) Missense mutation c.1040G>A was inherited paternally. (B) Missense mutation c.4056G>C was inherited paternally. (C) Missense mutation c.1526G>C was inherited maternally.

Fig.2 Sanger sequencing of the CFTR gene from P-2 and parents. The homozygous missense mutation c.2909G>A of CFTR was detected. Each of the parents showed heterozygous mutation c.2909G>A.

Fig.3 Sanger sequencing of the CFTR gene fromP-3 and parents. c.1116+ 1G>A and c.3062C>T compound heterozygous mutations of CFTR were detected. (A) Heterozygous mutations c.1116+ 1G>A was maternal. (B) Missense mutation c.3062C>T was paternal.

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