Mutations in the SLC12A6 gene have been associated with various disorders of the nervous system. Depending on the mutation type and inheritance, the SLC12A6-related symptoms can vary from very severe to mild.
Clinical features:
Mutations in the SLC12A6 gene can cause a severe autosomal recessive disorder the so-called hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), also known as Andermann syndrome. It is characterized by severe progressive neuropathy from infancy, brain abnormalities, developmental delay with or without seizures, scoliosis, contractures, tremor, hypotonia and dysmorphic features.
Mutations in the SLC12A6 gene have also been described to cause an autosomal dominant Charcot-Marie-Tooth (CMT) disease, characterized by neuropathy without intellectual disability or brain abnormalities. The prognosis of the disease is unclear, since only young patients with this disorder have been reported so far.
Prevalence:
The autosomal recessive disorder, HMSN/ACC, is mainly found in the French-Canadian population in the regions of Quebec. 1 of 23 in this population carry a mutation (c.2436delG) in the SLC12A6 gene and HMSN/ACC occurred 1 in 2,117 live births. The disease has been reported in other countries as well. Worldwide, HMSN/ACC is considered to be very rare.
The prevalence of CMT patients due to heterozygous SLC12A6 mutations cannot be estimated since there are only few reported cases so far.
Inheritance:
SLC12A6-related disorders can be inherited in an autosomal recessive and autosomal dominant manner.
The more severe disorder, HMSN/ACC, is inherited in an autosomal recessive manner. The parents and further family members who were heterozygous carriers of these mutations were healthy.
Mutations in the SLC12A6 gene have been associated with the autosomal dominant CMT. The affected patients mostly had de novo mutations and a much milder clinical presentation than the patients with HMSN/ACC.
SLC12A6