Liddle syndrome (LS), a monogenetic autosomal dominant disorder, is mainly characterized by early-onset hypertension and hypokalemia. Clinically, misdiagnosis or missing diagnosis is common, since clinical phenotypes of LS are variable and nonspecific. We report a family with misdiagnosis of primary aldosteronism (PA), but identify as LS with a pathogenic frameshift mutation of the epithelial sodium channel (ENaC) β subunit. DNA samples were collected from a 32-year-old proband and 31 other relatives in the same family. A designed panel including 41 genes associated with monogenic hypertension was screened using next-generation sequencing. The best candidate disease-causing variants were verified by Sanger sequencing. Genetic analysis of the proband revealed a novel frameshift mutation c.1838delC (p.Pro613Glnfs*675) in exon 13 of SCNN1B. This heterozygous mutation involved the deletion of a cytosine from a string of three consecutive cytosines located at codons 612 to 613 and resulted in deletion of the crucial PY motif and elongation of the β-ENaC protein. The identical mutation was also found in 12 affected family members. Amiloride was effective in alleviating LS for patients. There were no SCNN1A or SCNN1G mutations in this family. Our study emphasizes the importance of considering LS in the differential diagnosis of early-onset hypertension. The identification of a novel frameshift mutation of SCNN1B enriches the genetic spectrum of LS and has allowed treatment of this affected family to prevent severe complications.
Peng Fan, Chao-Xia Lu, Di Zhang, Kun-Qi Yang, Pei-Pei Lu, Ying Zhang, Xu Meng, Su-Fang Hao, Fang Luo, Ya-Xin Liu, Hui-Min Zhang, Lei Song, Jun Cai, Xue Zhang and Xian-Liang Zhou
Zeming Liu, Di Hu, Huang Yi Hui, Chen Si Chao, Zeng Wen, Zhou Ling, Zhou Wei, Wang Min, Feng Hai Feng, Wei Wei, Chao Zhang, Chen Dan Yang and Liang Guo
Objectives: Controversies regarding factors associated with distant metastasis in pediatric thyroid cancer remain among the scientific community. The aim of this study was to investigate factors influencing distant metastasis in pediatric thyroid cancer.
Methods: We reviewed 1376 patients (aged 2 to 18 years) with thyroid cancer treated between 2003 and 2014. Data collected and analyzed included sex, race, age at diagnosis, year of diagnosis, pathological type, number of tumor foci, tumor extension, T-stage, N-stage, surgical procedure, and radiation. Univariate and multivariate analyses were conducted to evaluate factors influencing distant metastasis of pediatric thyroid cancer.
Results: In the univariate analysis, factors influencing distant metastasis of thyroid cancer were age at diagnosis (P<0.001), N-stage (P<0.001), number of tumor foci (P=0.003), tumor extension (P<0.001), and T-stage (T1 vs. T2 [P=0.803], T3 [P<0.001], and T4 [P<0.001]). In multivariate analysis, factors influencing distant metastasis of thyroid cancer were age at diagnosis (P=0.001), N-stage (P<0.001), and T-stage (T1 vs. T3 [P=0.036] and T4 [P<0.001]). Sex, race, year of diagnosis, pathological type, number of tumor foci, tumor extension, surgical procedure, and radiation had no significant influence on distant metastasis (all P<0.05). Furthermore, according to chi-squared test, younger pediatric thyroid cancer patients with higher T- and N-stage are more likely to have distant metastasis.
Conclusion: Age at diagnosis, T-stage, and N-stage influence distant metastasis of thyroid cancer patients aged 2 to 18 years; accordingly, more radical treatments may need to be used for patients with those risk elements.