dHMN-5B

REEP1 | 2012

What Is dHMN-5B?

dHMN-5B is a type of CMT caused by autosomal dominant mutations in the REEP1 gene. This gene provides instructions for making a protein that supports the structure and function of the network of membranes within nerve cells. Mutations in the REEP1 gene disrupt this function, leading to impaired nerve signal transmission.

dHMN-5B is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.

Clinical Features

The age of symptom onset in dHMN-5B is variable, ranging from childhood to adulthood. As a motor neuropathy, dHMN-5B primarily affects the most distal points, with weakness and atrophy of the feet and hands, and little to no involvement of the sensory nerves. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.

dHMN-5B symptoms may include:

  • Weakness and atrophy in the feet and lower legs
  • Foot drop
  • Brisk reflexes
  • A steppage-style walking pattern
  • Foot deformities, including high arches, and hammertoes (clawed toes)
  • Progressive involvement of the hands
  • Difficulty with fine motor skills and manual dexterity
  • Additional symptoms not listed here

Disease Course

dHMN-5B shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Disease progression is generally slow, and life expectancy is not reduced.

Clinical Basics

Subtype
dHMN-5B

Classification
dHMN/HMN

Neuropathy Type
Axonal

Inheritance Pattern
autosomal dominant

Genetic Context

HGNC-Approved Gene Symbol
REEP1

Gene Full Name
Receptor Accessory Protein 1

HGNC Gene Alias(es)
C2ORF23

Chromosome
2p11.2

Zygosity of Responsible Variant
Heterozygous

Mitochondrial Involvement
Yes

Variant Mechanism
Loss of Function (LoF)

ClinVar Pathogenic Variants

View dHMN-5B ClinVar Variants

dHMN-5B OMIM Entry

dHMN-5B OMIM

REEP1 OMIM Entry

REEP1 OMIM

More Info

dHMN-5B Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

Exome Sequencing Identifies a REEP1 Mutation Involved in Distal Hereditary Motor Neuropathy Type V

Authors

Beetz, C., Pieber, T. R., Hertel, N., Schabhüttl, M., Fischer, C., Trajanoski, S., Graf, E., Keiner, S., Kurth, I., Wieland, T., Varga, R. E., Timmerman, V., Reilly, M. M., Strom, T. M., & Auer-Grumbach, M.

Publication Date
July 13, 2012

Updated: July 18, 2026 | By: K. Raymond

The Dorsal Root

More From The Dorsal Root


Close-up of a doctor’s hand holding a prescription pad while a patient’s wrist is wrapped with metal chains.


When Medicine Lost Its Compass

Evidence failed not because it was wrong, but because it was weaponized. I lived the downstream effects of that failure for more than a decade. This is what happens when medicine forgets that data always ends in a human being.


Illustrated graphic showing large ‘404’ numerals with people interacting with data screens and servers, alongside text reading ‘CMT Genetic Testing Error 404: Gene Not Found’ and ‘Examining Why Less Than Half of All Who Have Charcot-Marie-Tooth Disease Are Not Able to Obtain Genetic Confirmation of Their Disease.


Error 404: Gene Not Found

CMT genetic testing often fails to identify the cause of the disease, even when comprehensive panels are used. Here, we discuss why this happens, what genetic tests can and cannot do, and why a negative result still matters.


Illustrated cover graphic showing a split landform with branching directional arrows, two people with question marks above their heads, and the title ‘SORD Deficiency: Decoding This Newly Discovered and Confusing CMT Subtype.


CMT-SORD: What Is This Unique CMT Subtype?

CMT-SORD is a newly discovered CMT subtype driven by toxic sorbitol accumulation. This article explains how "SORD" works, why this subtype is different, and how it led to the fastest-moving therapeutic program in CMT history.