Categories: Nervous system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 603557 (gene) , 601382 (trait)

Links to MONDO diseases:

• MONDO:0011066: Charcot-Marie-Tooth disease type 4B1

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2023

Cross-species summary: Congenital polyneuropathy due to underproduction of myelin, which is exclusively affecting the peripheral nervous system. Similar to Charcot-Marie-Tooth disease in humans.

Species-specific name: congenital hypomyelinating polyneuropathy; HPN

Species-specific description: Cook et al. (2023): “Congenital hypomyelinating polyneuropathy (HPN) restricted to the peripheral nervous system was reported in 1989 in two Golden Retriever (GR) littermates [see OMIA:001292-9615 : Polyneuropathy, generic in Canis lupus familiaris]. Recently, four additional cases of congenital HPN in young, unrelated GRs were diagnosed via neurological examination, electrodiagnostic evaluation, and peripheral nerve pathology."

Molecular basis: Cook et al. (2023): “Whole-genome sequencing was performed on all four [affected Golden Retriever] …, and variants from each dog were compared to variants found across >1,000 other dogs, all presumably unaffected with HPN. Likely causative variants were identified for each HPN-affected GR.” The authors identified 3 likely causal variants in functional candidate genes MTMR2, MPZ and SH3TC2. “Cases 1 and 2 shared a homozygous MTMR2 (myotubulin related protein 2) variant located within the splice site at the end of exon 12 … . This G to A transition at CFA21: 5,387,227 (XM_038568229.1:c.1479+1G>A) is predicted to result in the loss of the splice donor site.” Please see the gene specific OMIA entries for details about the other variants.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breed: Golden Retriever.
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: