Researchers have linked a newly identified mutation affecting the HSPB1 gene to a rare subtype of Charcot-Marie-Tooth disease (CMT) in a recent case report from India.
The case report, “Charcot Marie Tooth disease 2F and a novel mutation from India,” was described by a team at the P. D. Hinduja National Hospital and Research Centre in Mumbai, India, in the journal Neurology India.
The patient, a 60-year-old man, was referred to the neurology department for bilateral progressive weakness and wasting affecting the lower limbs. He reported difficulty in pressing the brake and accelerator, and had a history of slippage of slippers, all of which had persisted for the past four years.
Other members of his family were also affected by these symptoms, the youngest of whom was 35 years old at disease onset.
No other signs of muscle weakness or sensory loss were reported. He had developed diabetes mellitus, which was under control with medication.
Physical evaluation revealed bilateral pes cavus, a deformity causing high arched feet characteristic of CMT. Examination of the central nervous system showed normal higher mental function and cranial nerves.
The clinical team identified weakness and wasting of the hand and foot muscles. Other muscles of the limbs were not affected, showing normal power and tone. Superficial sensation was also normal.
Despite the symptoms, the patient had normal body balance. He did, however, have high steppage gait, meaning he had to lift his leg higher to prevent his foot from scraping the ground due to an inability to properly flex the foot.
Based on his symptoms and family history, he was diagnosed with CMT, with greater damage to peripheral motor nerve cells (those that control movement) than sensory cells.
Genetic analysis revealed he had a mutation of the HSPB1 gene. The mutation was identified by researchers as R140G, leading to a substitution of a single amino acid from glycine to arginine. While other mutations of HSPB1 have previously been linked to CMT, this particular mutation had not been described before nor associated with the disease.
Mutations of this gene have been identified as a cause of CMT type 2F (CMT2F) and distal hereditary motor neuropathy (HMN) type II. The distinguishing feature of the two neuropathic disorders is that HMN patients suffer sensory loss, which was not found in the patient in this case, leading to the diagnosis of CMT2F.
To date, only six mutations of the HSPB1 gene have been described in families with HMN or CMT2F — Arg127Trp, Arg136Trp, Ser135Phe, Thr151Ile, Pro182Ser, and Pro182Leu. These have been identified in 4 percent of CMT2 cases, although its incidence remains unknown.
“Based on the above evidence, this HSPB1 variation can be classified as a probably significant variant,” the researchers said.