OMIA 002117-9615 : CHILD-like syndrome in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 308050

Mendelian trait/disorder: yes

Mode of inheritance: X-linked semi-dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

Species-specific name: Congenital cornification disorder; X-linked cutaneous mosaicism

Species-specific description: De Lucia et al. (2019): "Veterinary clinicians should be aware of cutaneous mosaicism and consider X-linked genodermatoses when seeing female cases with segmental cutaneous diseases like the one following the Blaschko’s lines."

Inheritance: De Lucia et al. (2019): "In heterozygous females, with an X-linked dominant or semidominant genodermatosis, . . . random inactivation of the X chromosome is responsible for the development of normal and abnormal skin segments distributed in a mosaic pattern. In fact, normal skin derives from progenitor cells in which the X-chromosome carrying the pathogenic variant has been inactivated, whereas stripes or patches of abnormal skin result from progenitor cells after the inactivation of the wild-type (normal) X-chromosome. X-linked cutaneous mosaicism can be heritable and is normally observed in heterozygous females."

Mapping: "Visual inspection of candidate genes located on the X-chromosome" enabled Bauer et al. (2017) to identify "a large deletion in the NSDHL gene, encoding NAD(P) dependent steroid dehydrogenase-like, a 3β-hydroxysteroid dehydrogenase involved in cholesterol biosynthesis."

Molecular basis: Bauer et al. (2017):"a deletion spanning 14,399 bp including the last three exons of the NSDHL gene . . . . The formal variant designation is chrX:120,749,179_120,763,577del14,399"

Clinical features: Bauer et al. (2017):"No abnormalities were found on the affected daughter during general physical examination except a stunted growth. Linear hyperplastic and partially alopecic lesions, covered with thick brown scales and clusters of dilated follicular ostia were the most prominent dermatological features (Figure 1). The lesions were distributed along Blaschko’s lines in a bilateral rather symmetrical fashion and were more evident on the limbs, the head, the neck and the dorsal trunk. The abdominal and inguinal skin appeared normal. Frond like hyperkeratotic lesions at the margin of all the pawpads with occasional horn-like projections were considered the most probable cause of the visible lameness. Cytological examination of the linear hyperplastic lesions, revealed the presence of variable numbers of coccoid bacteria and a large number of Malassezia yeasts which were suspected to substantially contribute to the pruritus and the offensive odor. Results of the blood tests and urinalysis were unremarkable."

De Lucia et al. (2019): "Alopecic scaly plaques following the Blaschko’s lines on the limbs, the head, the dorsal neck and the trunk, and severe foot pads hyperkeratosis were the most relevant lesions"

Pathology: Bauer et al. (2017):"The histopathological findings were identical in all biopsies . . . . Multifocally, the epidermis and the wall of the hair follicular infundibuli were moderately to severely hyperplastic with abrupt transition to normal skin. Within the hyperplastic area the infundibular epithelium was covered by thick layers of densely packed parakeratotickeratin which was distending the infundibuli. The parakeratotic keratin was often protruding above the epidermal surface. The size of the keratohyalin granules within the granular cell layers of the epidermis and the infundibular wall was within the normal range. Within the parakeratotic keratin, multifocally variable numbers of coccoid bacteria were present and occasionally the lumen of infundibuli contained degenerate neutrophils. Sebaceous glands appeared normal. The interfollicular epidermis was covered by moderate to large amounts of laminar to compact mostly orthokeratotic, but also some parakeratotic keratin. Within the keratin layers of the epidermis multifocally degenerate neutrophils, nuclear debris and small numbers of coccoid bacteria were present. Multifocally exocytosis of neutrophils was seen. Within the superficial dermis there was a mild pigmentary incontinence and a moderate perivascular infiltrate composed of neutrophils, mast cells and fewer lymphocytes."

Breed: Labrador Retriever.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
NSDHL NAD(P) dependent steroid dehydrogenase-like Canis lupus familiaris X NC_006621.3 (120720118..120754573) NSDHL Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

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
Labrador Retriever CHILD-like syndrome NSDHL deletion, gross (>20) CanFam3.1 X g.120,749,179_120,763,577del14 2017 28739597

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.
2019 De Lucia, M., Angileri, M., Bauer, A., Spycher, M., Jaggannathan, V., Denti, D., Di Diodoro, F., Ferro, S., Mezzalira, G., Welle, M., Leeb, T. :
X-linked cutaneous mosaicism in a dog. Vet Dermatol :, 2019. Pubmed reference: 31012178. DOI: 10.1111/vde.12748.
2017 Bauer, A., De Lucia, M., Jagannathan, V., Mezzalira, G., Casal, M.L., Welle, M.M., Leeb, T. :
A Large Deletion in the NSDHL Gene in Labrador Retrievers with a Congenital Cornification Disorder. G3 (Bethesda) 7:3115-3121, 2017. Pubmed reference: 28739597. DOI: 10.1534/g3.117.1124.
2008 Cadiergues, M.C., Patel, A., Shearer, D.H., Fermor, R., Miah, S., Hendricks, A. :
Cornification defect in the golden retriever: clinical, histopathological, ultrastructural and genetic characterisation. Vet Dermatol 19:120-9, 2008. Pubmed reference: 18477327. DOI: 10.1111/j.1365-3164.2008.00667.x.
1998 Lewis, D.T., Messinger, L.M., Ginn, P.E., Ford, M.J. :
A hereditary disorder of cornification and multiple congenital defects in five Rottweiler dogs Veterinary Dermatology 9:61-72, 1998.

Edit History


  • Created by Frank Nicholas on 15 Aug 2017
  • Changed by Frank Nicholas on 15 Aug 2017
  • Changed by Frank Nicholas on 21 Jan 2018
  • Changed by Frank Nicholas on 25 Apr 2019