OMIA:002849-9940 : Methylmalonic-coA mutase deficiency in Ovis aries (sheep)

Categories: Mortality / aging (incl. embryonic lethal) , Homeostasis / metabolism phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 609058 (gene) , 251000 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2024

Species-specific name: deficient homozygous haplotype MTRDHH1

Mapping: Braiek et al. (2024) "used phased 50 k single nucleotide polymorphism (SNP) genotypes and pedigree data to scan the genome of 6845 Manech Tête Rousse dairy sheep to search for deficiency in homozygous haplotypes (DHH). Five Manech Tête Rousse deficient homozygous haplotypes (MTRDHH1 to 5) were identified, with a homozygous deficiency ranging from 84 to 100%. These haplotypes are located on Ovis aries chromosome (OAR)1 (MTRDHH2 and 3), OAR10 (MTRDHH4), OAR13 (MTRDHH5), and OAR20 (MTRDHH1), and have carrier frequencies ranging from 7.8 to 16.6%. ... two DHH (MTRDHH1 and 2) were linked with decreased insemination success and/or increased stillbirth incidence."

Molecular basis: Braiek et al. (2024) "investigated the MTRDHH1 haplotype, which substantially increased stillbirth rate, and identified a single nucleotide variant (SNV) inducing a premature stop codon (p.Gln409*) in the methylmalonyl-CoA mutase (MMUT) gene by using a whole-genome sequencing approach. ... Reverse transcriptase-qPCR and western blotting on post-mortem liver and kidney biological samples showed a decreased expression of MMUT mRNA in the liver and absence of a full-length MMUT protein in the mutant homozygous lambs."

Clinical features: Braiek et al. (2024) "generated homozygous lambs for the MMUT mutation by at-risk mating between heterozygous carriers, and most of them died within the first 24 h after birth without any obvious clinical symptoms."

Breed: Manech Tête Rousse, France (Sheep) (VBO_0015121).
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
MMUT methylmalonyl-CoA mutase Ovis aries 20 NC_056073.1 (21912819..21872199) MMUT Homologene, Ensembl , NCBI gene


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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
1690 Manech Tête Rousse, France (Sheep) Methylmalonyl-CoA mutase deficiency MMUT nonsense (stop-gain) Naturally occurring variant Oar_rambouillet_v1.0 20 NC_040271.1:g.23776347G>A XM_004018875.4:c.1225C>T XP_004018923.1:p.(Q409*) 2024 38424485

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:002849-9940: Online Mendelian Inheritance in Animals (OMIA) [dataset].


2024 Ben Braiek, M., Moreno-Romieux, C., André, C., Astruc, J.M., Bardou, P., Bordes, A., Debat, F., Fidelle, F., Granado-Tajada, I., Hozé, C., Plisson-Petit, F., Rivemale, F., Sarry, J., Tadi, N., Woloszyn, F., Fabre, S. :
Searching for homozygous haplotype deficiency in Manech Tête Rousse dairy sheep revealed a nonsense variant in the MMUT gene affecting newborn lamb viability. Genet Sel Evol 56:16, 2024. Pubmed reference: 38424485. DOI: 10.1186/s12711-024-00886-7.

Edit History

  • Created by Imke Tammen2 on 02 May 2024
  • Changed by Imke Tammen2 on 02 May 2024