OMIA:002371-9940 : Microcephaly, MFSD2A-related in Ovis aries (sheep)

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:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2023

Species-specific name: congenital brain hypoplasia

Mapping: Rudd Garces et al. (2023) "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. (2023) "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. (2023) "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:

Symbol Description Species Chr Location OMIA gene details page Other Links
MFSD2A major facilitator superfamily domain containing 2A Ovis aries 1 NC_056054.1 (14573994..14586653) MFSD2A Homologene, Ensembl , NCBI gene

Variants

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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
1637 Kerry Hill (Sheep) Microcephaly, MFSD2A-related MFSD2A duplication Naturally occurring variant ARS-UI_Ramb_v2.0 1 g.14577421dup c.285dup p.(D96Rfs*9) XM_004001833.5; XP_004001882.2 2023 37921236

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002371-9940: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

Reference

2023 Rudd Garces, G., Letko, A., Häfliger, I.M., Müller, J., Herden, C., Nesseler, A., Wagner, H., Schmidt, M.J., Drögemüller, C., Lühken, G. :
MFSD2A frameshift variant in Kerry Hill sheep with microcephaly. Anim Genet , 2023. Pubmed reference: 37921236. DOI: 10.1111/age.13374.

Edit History


  • Created by Imke Tammen2 on 05 Aug 2021
  • Changed by Imke Tammen2 on 05 Aug 2021
  • Changed by Imke Tammen2 on 05 Nov 2023