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