Categories: Skeleton phene (incl. short stature & teeth) , Growth / size / body region phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 602744 (gene) , 222765 (trait)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2024

Inheritance: Boulling et al. (2024) report "a lethal form of recessive chondrodysplasia observed in 21 stillborn calves of the Aubrac breed of beef cattle."

Molecular basis: Boulling et al. (2024) "Using homozygosity mapping, whole genome sequencing of two affected individuals, and filtering for variants found in 1,867 control genomes, [the authors] reduced the list of candidate variants to a single deep intronic substitution in GNPAT (g.4,039,268G>A on Chromosome 28 of the ARS-UCD1.2 bovine genome assembly [omia.variant:1804])." The variant segregated with the disease in 21 affected animals and 26 available parents and in vivo and in vitro analysis identified that the variant "activates cryptic splice sites within intron 11 resulting in abnormal transcripts."

Clinical features: Boulling et al. (2024): "The 21 affected calves were stillborn and exhibited extremely disproportionate dwarfism characterized by craniofacial dysmorphism, short limbs with hypermobile joints, a distended abdomen prone to eventration, and low birth weight despite normal gestation length ... ." Further research after identification of the likely causal variant omia.variant:1804 "demonstrated that this deep intronic substitution was responsible not only for stillbirth but also for juvenile mortality in homozygotes and had a moderate but significant negative effect on muscle development in heterozygotes."

Breed: Aubrac (Cattle) (VBO_0000112).
Breeds in which the phene or likely causal variants have been documented. If a likely causal variant has been documented, see variant-specific breed information in the variant table. (Breed information may be incomplete).

Associated gene: