Novel Mutation Identified in Rare Form of CMT in Chinese Girl, Case Study Reports

Novel Mutation Identified in Rare Form of CMT in Chinese Girl, Case Study Reports

Researchers identified a novel mutation responsible for a rare form of Charcot-Marie-Tooth disease in a 13-year-old Chinese patient.

The case report, “A novel homozygous nonsense mutation in NEFL causes autosomal recessive Charcot-Marie-Tooth disease,” appeared in the journal Neuromuscular Disorders.

Mutations (errors) in the gene coding for the neurofilament light polypeptide (NEFL) – a key component of the structural machinery of nerve cells (or neurons) called the cytoskeleton – is the cause of a rare form of Charcot-Marie-Tooth (CMT) disease. This type of CMT is called autosomal dominant axonal Charcot-Marie-Tooth, or CMT2E, and it means that getting one copy of the mutated gene is sufficient to trigger the disease.

A pattern of what is known as autosomal recessive axonal form of Charcot-Marie-Tooth – meaning that in this case both copies of the gene need to carry the mutation for the disease to manifest – is much rarer and has only been identified, until now, in two patients.

These patients exhibited a set of common features, including disease onset during childhood with severe damage to peripheral nerves.

Now, authors describe a case of a 13-year-old Chinese girl carrying a mutation that caused autosomal recessive axonal Charcot-Marie-Tooth.

The child was born from consanguineous parents (in genetics, this means the parents are second cousins or closer and share a common ancestor). At birth she had no neuromuscular disorders and was capable of sitting at 6 months of age, but was unable to stand or walk until she was around 1 year old. She then began to develop gait disturbance and weakness in her lower extremities until she was 10 years old. At this age she had to use a tailored ankle-foot orthosis.

As in the other two cases, this girl presented “marked delay in motor milestones, distal wasting of legs and pes cavus deformities,” the authors said in the report.

A biopsy to the sural nerve in the leg showed a severe loss of large myelinated fibers.

The authors conducted additional analyses, and using targeted next-generation sequencing, identified a new mutation in the NEFL gene as the potential cause for the disease spectrum in the patient. The mutation may lead to a reduction in the levels of the NEFL protein, which may explain the absence of neurofilaments, authors stated.

Overall, “we report a novel homozygous nonsense NEFL mutation causing autosomal recessive CMT. It expands the mutation spectrum of NEFL-related CMT [Charcot-Marie-Tooth],” the case report concluded.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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