Categories: Cardiovascular system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 613172 (trait) , 613171 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2014

Species-specific symbol: DCM

Inheritance: Harmon et al. (2017): "The occurrence of early onset DCM [dilated cardiomyopathy] in multiple closely related standard schnauzers suggests a familial predisposition in this breed. Pedigree analysis confirmed common ancestry for all DCM affected dogs with a most likely autosomal recessive mode of inheritance."

Molecular basis: Leach et al. (2014) report that dilated cardiomyopathy in standard schnauzers is associated with a homozygous 22 bp deletion in RBM20. Leach et al. (2021): "homozygosity for the variant was highly associated with DCM and approximately 80% shortened lifespan."

Clinical features: Harmon et al. (2017): "describe the clinical features of DCM in standard schnauzers. Medical records for 15 standard schnauzers diagnosed with DCM were reviewed. The median age at diagnosis of DCM was 1.6 yr, with all dogs developing left-sided congestive heart failure (CHF). The median age of onset of CHF was 1.6 yr, and was significantly shorter in males (1.5 yr) than for females (2.35 yr). The median survival time after diagnosis of CHF was 22 days, and was shorter in males (13 days) than females (62 days)." Median lifespan is shorter (3.06 years) in standard schnauzers homozygous for the mutation compared to those heterozygous (15.11 years) or wild-type (15.18 years) (Leach et al., 2022) [IT thanks DVM student Caitlin Henning for contribution to this entry in April 2022].

Pathology: In the study by Harmon et al. (2017), postmortems performed on 5 SSNZ with DCM revealed moderate to marked cardiomegaly with biventricular dilation in all dogs. Histopathological examination performed on the left ventricle and interventricular septum showed myocyte degeneration in 4 out of 5 SSNZ, and increased interstitial fibrosis and myocyte attenuation in 3 SSNZ. [IT thanks DVM student Regis Tang, who provided the basis of this contribution in April 2022.]

Prevalence: Leach et al. (2022) genotyped 2136 samples from 14 different dog breeds for the associated RBM20 variant. "... approximately 21% of all tested SSNZ [standard schnauzer] samples carried at least one allele of the RBM20 variant, with 93% of those samples testing HET for the gene variant. Only 1.5% of the tested SSNZ samples were HOM for the gene variant. ... The RBM20 variant was also identified in GSNZ [giant schnauzer] dogs and was associated with DCM and premature death. The gene variant was not found in any of the 36 samples from breeds other than SSNZ or GSNZ."

Breeds: Giant Schnauzer (Dog) (VBO_0200604), Schnauzer, Standard (Dog) (VBO_0201189).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: