PMC10149701_01
Pedigree of the patient family and Sanger analysis for the mosaic mutation in CLCKNB. (A) II2 indicates the patient, I1 and I2 indicate the patient's parents; both carried a heterozygous mutation of the CLCNKB gene, II1 indicates the patient's elder sister with similar clinical symptoms. (B) Next-generation sequencing detected c.1257delC in the CLCNKB gene in the patient and her parents. (C) Next-generation sequencing detected c.595G > T in the CLCNKB gene in the patient and her parents. (D) Sanger sequencing to confirm the mutation of the CLCNKB gene c.595G > T (p.E199*) in the patient's family.
fped-11-1034923-g001.jpg
PMC10149701_01_fped-11-1034923-g001.jpg
F1
The patient's elder sister started showing progressive metabolic alkalosis and hypokalemia at 18 days of life (Figure 1A). A trio-clinical exome sequencing (AmCare Genomics Lab, Guangzhou) was performed on the patient and her parents. A frameshift mutation c.1257delC (p.M421Cfs*58) in exon 13 of the CLCNKB gene was found in the patient, which was inherited from the patient's asymptomatic father (Figure 1A). This mutation was also verified in the patient's mother with a VAF of 20.8% (Figure 1B,C). Therefore, we speculated that mutation c.595G > T (p.E199*) in the CLCNKB gene was a low-grade mosaic mutation. Sanger sequencing was used to confirm the low VAF mutation (Figure 1D).