Dados do Trabalho

Título

Novel SH3TC2 Gene Mutation in a Brazilian Individual with Charcot-Marie-Tooth disease type 4C

RESUMO

Case Presentation
A 42-year-old Brazilian male with a history of hypertension was admitted to our medical department due to progressive numbness and weakness in the lower extremities. The patient described his motor performance as relatively poor compared to his peers since childhood. At age 39, he noticed decreased sensation in his feet, causing difficulty in wearing shoes and walking. He slowly developed progressive weakness of lower limbs, unsteadiness, and clumsiness at the age of 41. He is the son of a consanguineous couple and has a sister with similar symptoms.
Physical exam was remarkable for pes planus deformity, stork legs, and scoliosis. Neurological examination revealed slowing of saccades, hypoacusis, occasional tongue fasciculations, and mild facial diplegia. He had weakness of the proximal (4+/5) and distal lower limbs (4-/5) with relatively preserved muscle strength of the upper limbs. Sensation of vibration, light touch, and pinprick were markedly reduced in both lower extremities. Hyporeflexia, a broad-based gait, and a positive Romberg sign were also noted.
Biochemical analysis showed elevated serum creatine kinase (1278 U/L) and neuron-specific enolase (10 μg/L). His complete blood cell count, electrolytes, HbA1C, Vitamin B12, folic acid, liver, thyroid, and kidney function tests were all unremarkable. Autoimmune panel, serum tumor markers, and cerebrospinal fluid analysis disclosed no abnormalities.
Electrophysiological studies indicated a symmetrical, length-dependent, demyelinating sensorimotor polyneuropathy with axonal loss and markedly reduced motor conduction velocity. Genetic testing reveled a novel homozygous pathogenic variant, c.1144G>T p.Glu382*, in SH3TC2.

Discussion
Our patient presented with the typical features of Charcot-Marie-Tooth disease type 4C (CMT4C), including demyelinating neuropathy, foot deformity, scoliosis, and cranial nerve involvement. We identified a new mutation in SH3TC2, predicted to be disease causing since it results in a very premature stop codon at amino acid position 382 and a shortened protein with a potentially abnormal function. The identified variant is absent in 141000 control chromosomes from gnomAD; it has never been reported in the medical literature or in the ClinVar database.

Final Comment
In conclusion, we present a Brazilian patient with CMT4C associated with a novel mutation of SH3TC2. This case highlights the importance of considering rare diagnoses in the new generation sequencing era.

Palavras Chave

Charcot-Marie Tooth disease, hereditary motor and sensory neuropathy, CMT4C, SH3TC2, Novel variant, Brazil

Área

Neurogenética