Genomic coordinate (human 10:119,651,380 BAG3) & (mouse 7:128,125,340 Bage3).
Cytoband (human 10q26.11 BAG3) & (mouse 7q Bage3).
“Hereditary Distal-Motor Neuropathy”, Victor McKusick, Mendelian Inheritance in Man’, 1966 (BAG3) icd10=G60.0
Hereditary distal-motor neuropathy is a group of genetically heterogeneous disorders causing progressive, length-dependent degeneration of motor neurons. It results in muscle weakness and atrophy, predominantly in the hands and feet. Symptoms typically begin in adolescence or adulthood, often causing gait difficulties, with a generally normal life expectancy as the disease is typically not fatal.
Key Aspects of dHMN
Symptoms: Initial symptoms often include distal muscle weakness in the lower limbs, such as foot drop or high-arched feet, with later progression to hand weakness (weakness and wasting of muscles). Rare, severe types may include breathing difficulties or vocal cord paresis.
Types/Genetics: There are numerous types (e.g., dHMN Type V, Type II) with autosomal dominant, autosomal recessive, or X-linked inheritance. Over 30 genes are associated with the condition.
Diagnosis: Electrophysiology shows normal sensory conduction but abnormal motor conduction, differentiating it from Charcot-Marie-Tooth disease (which affects sensation).
Treatment: There is no cure, but management focuses on relieving symptoms, physical therapy, and using braces or orthopedic surgery for foot deformities.
Hereditary Distal-Motor Neuropathy-15 (HMND15) is an adult-onset, autosomal dominant form with incomplete penetrance. HMND15 affected individuals exhibit a slowly progressive and symmetric distal weakness and atrophy of lower limb muscles, along with absent Achille reflexes. Sensory deficits are not present.
There is evidence that hereditary distal-motor neuropathy is caused by mutation in the BCL-2 associated athanogene (BAG3) gene encoded on genomic coordinate 10:119,651,380 and cytoband 10q26.11 in humans.
BAG family molecular chaperone regulator-3 is a protein that in humans is encoded by the BAG3 gene. BAG3 is involved in chaperone-assisted selective autophagy.
