The EGR2 gene

EGR2 is the name of one of the genes that can cause Dejerine-Sottas. The acronym stands for Early Growth Response 2.

Location

The EGR2 gene is located at 10q21.1-q22.1 (on the long arm of chromosome 10, from position 22.1 to position 22.1).

From genotype to phenotype

Mutations in this gene can cause Charcot-Marie-Tooth disease, type 1D, or autosomal dominant Dejerine-Sottas neuropathy.

Timmerman et al. (1999) screened 170 unrelated neuropathy patients and identified 2 with Dejerine-Sottas neuropathy (DSN; 145900) who had a heterozygous R359W mutation (129010.0004) in the alpha-helix domain of the first zinc finger of EGR2. Sural nerve biopsy showed a severe loss of myelinated and unmyelinated fibers, classic onion bulbs, and focally folded myelin sheaths. Boerkoel et al. (2001) reported 2 additional DSN patients with the R359W mutation and suggested that it is the most common neuropathy-associated EGR2 mutation and consistently causes DSN. The expressivity ranged from that typical for DSN to a more rapidly progressive neuropathy that can cause death by age 6 years. Furthermore, in contrast to patients with typical DSN, patients with the R359W EGR2 mutation had more respiratory compromise and cranial nerve involvement.

Boerkoel et al. (2001) reported 2 patients with Dejerine-Sottas neuropathy (145900) and an arg359-to-trp (R359W) mutation in the EGR2 gene. In both patients, the mutation appeared to be de novo dominant. One patient presented with hypotonia and hip dysplasia immediately after birth. She gained minimal use of her hands and feet during the first 6 months of life and then gradually lost motor function, developing paralysis distal to the knees and elbows by 2 years of age. A sural nerve biopsy demonstrated a marked decrease of myelinated fibers, evidence of demyelination and remyelination, and onion bulb formation. The course of her disease was characterized by increasing difficulty swallowing and breathing, and she died of respiratory failure at 6 years of age. The other patient had difficulty grasping objects and strabismus secondary to lateral recti weakness by 4 to 5 months of age. At 3 years of age, she had severe distal muscle weakness and atrophy, areflexia, and decreased pain and temperature sensation; in the lower extremities, she had less severe distal muscle weakness and atrophy, hyporeflexia, and intact sensation. As a complication of her hand involvement, she developed bilateral fixed contractures of the fourth and fifth fingers by 15 years of age. At 3 years of age nerve conduction velocities could not be measured in the median and ulnar nerve, but tibial nerve conduction velocity was 8 m/s. Sural nerve biopsy showed typical changes of DSN, including onion bulb formation. She developed severe thoracolumbar scoliosis, requiring spinal fusion at 15 years of age. At age 22 years she was following a rigorous physical exercise program, including weight lifting and walking on a treadmill, and she had completed a university education.