OMIA 001867-9940 : Lissencephaly and cerebellar hypoplasia in Ovis aries |
In other species:
dog
,
domestic cat
Possibly relevant human trait(s) and/or gene(s) (MIM number):
257320
Mendelian trait/disorder:
yes
Mode of inheritance:
Autosomal Recessive
Considered a defect:
yes
Key variant known:
yes
Year key variant first reported:
2013
Species-specific symbol:
LCH
History:
Pérez et al. (2013) provided the first report in the peer-reviewed literature of this disorder in a particular breed of sheep.
Inheritance:
As reported by Pérez et al. (2013), "The analysis of the three pedigrees, including 14 affected animals . . . was consistent with a monogenic autosomal recessive inheritance".
Mapping:
By conducting a GWAS/homozygosity-mapping analysis on 7 affected and 33 normal Churra sheep, each genotyped with the OvineSNP50 SNP Chip (yielding 47,864 informative SNPs), Suárez-Vega et al. (2013) mapped this disorder to a 4.8Mb region on chromosome OAR4.
Molecular basis:
Sequencing of the most likely functional candidate gene in the candidate region (see Mapping section) enabled Suárez-Vega et al. (2013) to identify the causative mutation: "a deletion of 31 bp (c.5410_5440del) in predicted exon 36 of RELN, resulting in a premature termination codon. A functional analysis of this mutation revealed decreased levels of RELN mRNA and a lack of reelin protein in the brain cortex and blood of affected lambs."
Clinical features:
Pérez et al. (2013) reported this disorder in "42 newborn lambs from a pure Churra breed flock, with clinical signs of weakness, inability to walk, difficulty in sucking and muscular rigidity observed immediately after birth. All the lambs showed near-total agyria with only a rudimentary formation of few sulci and gyri, and a severe cerebellar hypoplasia."
Pathology:
As explained by Pérez et al. (2013), "The pathological features reported are consistent with the type LCH-b (lissencephaly with cerebellar hypoplasia group b) defined in human medicine".
Breed:
Churra.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| RELN | reelin | Ovis aries | 4 | NC_019461.2 (45182202..44644143) | RELN | Homologene, Ensembl, NCBI gene |
Variants
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| Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Churra | Lissencephaly and cerebellar hypoplasia | RELN | deletion, gross (>20) | a deletion of 31 bp (c.5410_5440del) in predicted exon 36 of RELN, resulting in a premature termination codon | 2013 | 24260534 |
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
| 2013 | Pérez, V., Suárez-Vega, A., Fuertes, M., Benavides, J., Delgado, L., Ferreras, M.C., Arranz, J.J. : | |
| Hereditary lissencephaly and cerebellar hypoplasia in Churra lambs. BMC Vet Res 9:156, 2013. Pubmed reference: 23938146. DOI: 10.1186/1746-6148-9-156. | ||
| Suárez-Vega, A., Gutiérrez-Gil, B., Cuchillo-Ibáñez, I., Sáez-Valero, J., Pérez, V., García-Gámez, E., Benavides, J., Arranz, J.J. : | ||
| Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in Sheep. PLoS One 8:e81072, 2013. Pubmed reference: 24260534. DOI: 10.1371/journal.pone.0081072. |
Edit History
- Created by Frank Nicholas on 16 Aug 2013
- Changed by Frank Nicholas on 16 Aug 2013
- Changed by Frank Nicholas on 24 Nov 2013