PMID- 34791225
OWN - NLM
STAT- MEDLINE
DCOM- 20220308
LR  - 20220716
IS  - 2160-1836 (Electronic)
IS  - 2160-1836 (Linking)
VI  - 12
IP  - 2
DP  - 2022 Feb 4
TI  - ABHD5 frameshift deletion in Golden Retrievers with ichthyosis.
LID - 10.1093/g3journal/jkab397 [doi]
LID - jkab397
AB  - Ichthyoses are hereditary skin disorders characterized by the formation of scales 
      and defects in the outermost layer of the epidermis. In dogs, at least six 
      different breed-specific ichthyoses including a relatively common PNPLA1-related 
      autosomal recessive ichthyosis in Golden Retrievers are known. In this study, we 
      investigated 14 Golden Retrievers with scales that were not homozygous for the 
      mutant PNPLA1 allele suggesting a genetically distinct new form of ichthyosis. 
      Histopathological examinations showed lamellar, orthokeratotic hyperkeratosis, 
      and mildly hyperplastic epidermis that led to the diagnosis of a nonepidermolytic 
      ichthyosis. Combined linkage and homozygosity mapping in 14 cases and 30 
      nonaffected family members delimited a critical interval of  approximately 12.7 Mb on 
      chromosome 23. Whole-genome sequencing of an affected dog revealed a single 
      protein-changing variant within this region that was not present in 795 control 
      genomes. The identified variant is a 14 bp deletion in the ABHD5 gene 
      (c.1006_1019del), leading to a frameshift and altering the last 14 codons 
      p.(Asp336Serfs*6). The genotypes at this variant showed perfect cosegregation 
      with the ichthyosis phenotype in a large family comprising 14 cases and 72 
      controls. ABHD5 encodes an acyltransferase required for lipid metabolism. In 
      humans, variants in ABHD5 cause Chanarin-Dorfman syndrome, a neutral lipid 
      storage disease with ichthyosis. Our data in dogs together with the knowledge on 
      the effects of ABHD5 variants in humans strongly suggest ABHD5:c.1006_1019del as 
      candidate causative genetic variant for a new canine form of ichthyosis, which we 
      propose to designate as Golden Retriever ichthyosis type 2 (ICH2).
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of Genetics 
      Society of America.
FAU - Kiener, Sarah
AU  - Kiener S
FAU - Wiener, Dominique J
AU  - Wiener DJ
FAU - Hopke, Kaitlin
AU  - Hopke K
FAU - Diesel, Alison B
AU  - Diesel AB
FAU - Jagannathan, Vidhya
AU  - Jagannathan V
FAU - Mauldin, Elizabeth A
AU  - Mauldin EA
FAU - Casal, Margret L
AU  - Casal ML
FAU - Leeb, Tosso
AU  - Leeb T
AUID- ORCID: 0000-0003-0553-4880
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - G3 (Bethesda)
JT  - G3 (Bethesda, Md.)
JID - 101566598
RN  - EC 2.3.1.51 (1-Acylglycerol-3-Phosphate O-Acyltransferase)
SB  - IM
MH  - *1-Acylglycerol-3-Phosphate O-Acyltransferase/genetics
MH  - Animals
MH  - Dogs
MH  - Frameshift Mutation
MH  - Gene Deletion
MH  - *Ichthyosiform Erythroderma, Congenital/genetics/pathology
MH  - *Ichthyosis/genetics/pathology/veterinary
MH  - *Ichthyosis, Lamellar/genetics/veterinary
MH  - *Lipid Metabolism, Inborn Errors/genetics/pathology
MH  - Plant Breeding
PMC - PMC9210301
OTO - NOTNLM
OT  - Canis lupus familiaris
OT  - animal model
OT  - dermatology
OT  - dog
OT  - genodermatosis
OT  - lipid storage disorder
OT  - metabolism
OT  - precision medicine
OT  - veterinary medicine
EDAT- 2021/11/19 06:00
MHDA- 2022/03/09 06:00
PMCR- 2021/11/15
CRDT- 2021/11/18 07:23
PHST- 2021/09/24 00:00 [received]
PHST- 2021/11/05 00:00 [accepted]
PHST- 2021/11/19 06:00 [pubmed]
PHST- 2022/03/09 06:00 [medline]
PHST- 2021/11/18 07:23 [entrez]
PHST- 2021/11/15 00:00 [pmc-release]
AID - 6428539 [pii]
AID - jkab397 [pii]
AID - 10.1093/g3journal/jkab397 [doi]
PST - ppublish
SO  - G3 (Bethesda). 2022 Feb 4;12(2):jkab397. doi: 10.1093/g3journal/jkab397.