Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 614397 (gene) , 616486 (trait)

Links to relevant human diseases in MONDO:

• MONDO:0014660: microcephaly 15, primary, autosomal recessive

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2023

Species-specific name: congenital brain hypoplasia

Mapping: Rudd Garces et al. (2024) "used a homozygosity mapping approach to identify regions of homozygosity with alleles shared by five SNP array-genotyped affected [Kerry Hill] lambs ... . Further analysis of the regions of homozygosity revealed only a single region [chr1:12 703 054–14 922 562] that was not homozygous in any unaffected sheep."

Molecular basis: Rudd Garces et al. (2024) "sequenced the genome of one affected [Kerry Hill] lamb, and comparison with 115 control genomes revealed a single private protein-changing variant. This frameshift variant, MFSD2A: c.285dupA, p.(Asp96fs*9), represents a 1-bp duplication predicted to truncate 80% of the open reading frame. ... Sanger sequencing confirmed the homozygous genotype in the seven affected lambs. Genotypes at the MFSD2A: c.285dupA variant perfectly co-segregated with the phenotype in the studied animals ... ."

Clinical features: Rudd Garces et al. (2024) "investigated an early-onset neurodegenerative disorder observed in seven lambs of purebred Kerry Hill sheep. Clinical signs included inability to stand or severe ataxia, convulsions, and early death. Diagnostic imaging and brain necropsy confirmed microcephaly."

Breed: Kerry Hill (Sheep) (VBO_0001468).
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: