Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 610007 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: unknown

Key variant known: yes

Year key variant first reported: 2023

Cross-species summary: This phenotype is characterized by hyposegmented nuclei of granulocytes. The phenotype resembles Pelger-Huët anomaly, but is caused by variants in the LMBR1L gene.

Species-specific description: The phenotype has initially been termed Pelger-Huët anomaly due to the phenotypic similarity with human Pelger-Huët anomaly. However, the human Pelger-Huët anomaly is caused by variants in the LBR gene, while this entry refers to an LMBR1L-related phenotype characterized by hyposegmented granulocytes.

History: Due to the phenotypic similarity with human Pelger-Huët anomaly, Latimer et al. (2000) initially hypothesized about an autosomal semidominant inheritance with embryonic lethality in homozygous mutant dogs. With the identification of the causative genetic variant in the LMBR1L gene, an autosomal recessive mode of inheritance has been conclusively established. The trait is probably not associated with any gross health problems and is not homologous to human Pelger-Huët anomaly.

Mapping: Lourdes Frehner et al. (2023): "Genome-wide association mapped the HG locus to chromosome 27 and established an autosomal recessive mode of inheritance. "

Molecular basis: Lourdes Frehner et al. (2023): "Whole genome sequencing identified a splice site variant in LMBR1L, c.191+1G>A, as most likely causal variant for the HG phenotype. The mutant allele abrogates the expression of the longer X2 isoform but does not affect transcripts encoding the shorter X1 isoform of the LMBR1L protein."

Prevalence: Lourdes Frehner et al. (2023): "The homozygous mutant LMBR1L genotype associated with HG is common in Australian Shepherd Dogs and was found in 39 of 300 genotyped dogs (13%)."

Breed: Australian Shepherd (Dog) (VBO_0200095).
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: