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Background  Hereditary sensory and autonomic neuropathy (HSAN) type II is a group of extremely rare autosomal recessive neurological disorders with heterogeneous clinical and genetic characteristics.    Methods  We performed high-depth next-generation targeted sequencing using a custom-ordered “HSAN” panel, covering  WNK1 ,  NTRK1 ,  NGF ,  SPTLC1  and  IKBKAP  genes, to identify pathogenic variants of the proband as well as the family members. We also performed whole exome sequencing to further investigate the potential occurrence of additional pathogenic variants in genes that were not covered by the “HSAN” panel. Quantitative real-time PCR was used to identify pathogenic copy number variations (CNVs) and to analyze the mRNA level of WNK1 gene of the family. Western blot analysis was performed to evaluate the WNK1 protein expression level.    Results  After sequencing, a novel nonsense variant (c.2747 T > G, p.Leu916Ter) in exon 9 of  WNK1  gene was identified in two patients (hemizygous) and their mother (heterozygous). This variant is absent in all public databases as well as in 600 Han Chinese healthy controls. The region of this variant is evolutionary highly conserved. Furthermore, by quantitative real-time PCR using DNA of the pedigree, we revealed a large deletion containing the whole  WNK1  gene in two patients. The  WNK1  expression levels of the patients were significantly reduced.    Conclusions  Our study firstly revealed that the coexistence of a novel  WNK1  nonsense variant and a CNV resulted in HSAN type IIA in a Han Chinese family.    Electronic supplementary material  The online version of this article (10.1186/s12881-019-0828-5) contains supplementary material, which is available to authorized users.

The coexistence of a novel WNK1 variant and a copy number variation causes hereditary sensory and autonomic neuropathy type IIA