On this page, you will find information about a genetic change that was identified in a UDN participant. We are trying to find others with the same or similar condition.

Sharing information on this website is not a requirement of UDN participation. Only descriptions about participants who give explicit consent will appear here.

Date of Report

Nov 21, 2016

Full Name

WNK lysine deficient protein kinase 1

Chromosome 12 (12p13.33)


The WNK1 gene codes for a serine/threonine protein kinase (Xu et al., 2000).

Database Links

GeneCards: GC12P00073

Genetics Home Reference: WNK1 Gene

NCBI Gene: 65125

OMIM: 605232

UniProtKB/Swiss-Prot: Q9H4A3

Clinical Significance

Changes in the WNK1 gene have been found in individuals with hereditary sensory and autonomic neuropathy II and pseudohypoaldosteronism type IIC.

A change in the WNK1 gene was identified in a UDN participant. Research is underway to see if this change is causing symptoms in this patient.

The participant, a 49-year-old female with muscle weakness, balance problems, clumsiness, muscle twitching (fasiculations) and cramps, abnormal heart rhythm (second-degree AV block), episodes of high potassium (hyperkalemia), restrictive lung disease, double vision (diplopia), and seizures was found to carry the following genetic change in the WNK1 gene: c.2336C>T/p.A779V.

Gene WNK1
Inheritance Pattern Autosomal recessive
Position chr12: 987490
Transcript NM_018979
DNA Change c.2336C>T
Protein Change p.A779V

The patient was in excellent health until age 45 when she started to notice muscle weakness and difficulty keeping up while playing sports.  Her muscle weakness has continued to worsen and she now has balance problems, muscle twitching (fasciculations) and cramps, and difficulty with coordination. She has significant respiratory muscle weakness and requires nocturnal bi-level ventilation (BiPAP).

The patient has double vision (diplopia on lateral gaze) with weakness (opthalmoplegia) and started having seizures (left temporal lobe focus). These seizures are now controlled with carbamazepine treatment and a pacemaker.

The patient also has an abnormal heart rhythm (second-degree AV block) and had a pacemaker implanted at age 48. Based on recent imaging findings, she has probable early heart disease (cardiomyopathy).

She has been diagnosed with a potassium channel disease (channelopathy) with impaired renal excretion, and has had several episodes of extreme high potassium (hyperkalemia) with dramatic ECG changes, respiratory failure, and very low serum phosphate.

The patient also has stage 3 thyroid cancer (multifocal papillary).

Some of her other features include:

  • Protruding shoulder blades (scapular winging)
  • Abnormal muscle biopsies (abundance of “moth eaten” fibers, increased sub-sarcolemmal accumulation of mitochondria, disruption of internal architecture of type II fibers)
  • Cytochrome c oxidase deficiency
  • Multiple mitochondrial DNA deletions
  • Low blood sugar (hypoglycaemia)
  • Low white blood cell levels (leukopenia)
  • Mild anemia (likely hemolytic)
  • Cerebral folate deficiency (high levels of anti-folate antibodies
  • Elevated IgM
  • Raynaud’s disease
  • Abnormal calcification in the kidneys (diffuse renal cortical nephrocalcinosis with retraction and scarring of cortex)
  • Low urea excretion in urine
  • High creatinine excretion in urine

Amino acid abnormalities (elevated amino acid levels in urine, decreased amino acid levels in cerebrospinal fluid)

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