A frameshift insertion in FA2H causes a recessively inherited form of ichthyosis congenita in Chianina cattle.

Jacinto, Joana G P; Häfliger, Irene M.; Veiga, Inês M. B.; Letko, Anna; Gentile, Arcangelo; Drögemüller, Cord (2021). A frameshift insertion in FA2H causes a recessively inherited form of ichthyosis congenita in Chianina cattle. Molecular genetics and genomics : MGG, 296(6), pp. 1313-1322. Springer 10.1007/s00438-021-01824-8

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The aim of this study was to characterize the phenotype and to identify the genetic etiology of a syndromic form of ichthyosis congenita (IC) observed in Italian Chianina cattle and to estimate the prevalence of the deleterious allele in the population. Sporadic occurrence of different forms of ichthyosis including IC have been previously reported in cattle. However, so far, no causative genetic variant has been found for bovine IC. Nine affected cattle presenting congenital xerosis, hyperkeratosis and scaling of the skin as well as urolithiasis and cystitis associated with retarded growth were examined. Skin histopathology revealed a severe, diffuse orthokeratotic hyperkeratosis with mild to moderate epidermal hyperplasia. The pedigree records indicated a monogenic recessive trait. Homozygosity mapping and whole-genome sequencing allowed the identification of a homozygous frameshift 1 bp insertion in the FA2H gene (c.9dupC; p.Ala4ArgfsTer142) located in a 1.92 Mb shared identical-by-descent region on chromosome 18 present in all cases, while the parents were heterozygous as expected for obligate carriers. These findings enable the selection against this sub-lethal allele showing an estimated frequency of ~ 7.5% in Chianina top sires. A sporadic incidence of mild clinical signs in the skin of heterozygous carriers was observed. So far, pathogenic variants affecting the encoded fatty acid 2-hydroxylase catalyzing the synthesis of 2-hydroxysphingolipids have been associated with myelin disorders. In conclusion, this study represents the first report of an FA2H-related autosomal recessive inherited skin disorder in a mammalian species and adds FA2H to the list of candidate genes for ichthyosis in humans and animals. Furthermore, this study provides a DNA-based diagnostic test that enables selection against the identified pathogenic variant in the Chianina cattle population. However, functional studies are needed to better understand the expression of FA2H in IC-affected Chianina cattle.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Other Institutions > Office of the Dean
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Jacinto, Joana, Häfliger, Irene Monika, Berenguer Veiga, Inês Margarida, Letko, Anna, Drögemüller, Cord

Subjects:

600 Technology > 630 Agriculture
500 Science > 590 Animals (Zoology)
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1617-4615

Publisher:

Springer

Language:

English

Submitter:

Cord Drögemüller

Date Deposited:

13 Oct 2021 12:47

Last Modified:

10 Apr 2024 14:11

Publisher DOI:

10.1007/s00438-021-01824-8

PubMed ID:

34599683

Uncontrolled Keywords:

Bovine Fatty acid 2-hydroxylase Genodermatoses Precision medicine Skin Urolithiasis

BORIS DOI:

10.48350/159984

URI:

https://boris.unibe.ch/id/eprint/159984

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