Epidermal barrier abnormalities in exfoliative ichthyosis with a novel homozygous loss-of-function mutation in CSTA.
Autosomal recessive exfoliative ichthyosis (AREI) results from mutations in CSTA, encoding cysteine protease inhibitor A (cystatin A). We present a 25-year-old man from Iran with consanguineous parents, who presented with congenital erythroderma, hyperhidrosis and diffuse hyperkeratosis with coarse palmoplantar peeling of the skin, aggravated by exposure to water and by occlusion. Candidate gene analysis revealed a previously unknown homozygous loss-of-function mutation c.172C>T (p.Arg58Ter) in CSTA, and immunostaining showed absence of epidermal cystatin A, confirming the diagnosis of AREI. Ultrastructural analysis by transmission electron microscopy showed normal degradation of corneodesmosomes, mild intercellular oedema in the spinous layer but not in the basal layer, normal-appearing desmosomes, and prominent keratin filaments within basal keratinocytes. Thickness of cornified envelopes was reduced, lamellar lipid bilayers were disturbed, lamellar body secretion occurred prematurely and processing of secreted lamellar body contents was delayed. These barrier abnormalities were reminiscent of (albeit less severe than in) Netherton syndrome, which results from a deficiency of the serine protease inhibitor LEKTI. This work describes ultrastructural findings with evidence of epidermal barrier abnormalities in AREI.
Department of Dermatology and Venereology, Medical University Innsbruck, Innsbruck, Austria.
V
V
Moosbrugger-Martinz
Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
A
A
Jalili
Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
A S
AS
Schossig
Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
K
K
Jahn-Bassler
Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
J
J
Zschocke
Department of Dermatology and Venereology, Medical University Innsbruck, Innsbruck, Austria.
M
M
Schmuth
Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
G
G
Stingl
Center for Dermatogenetics, Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
K M
KM
Eckl
Center for Dermatogenetics, Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
H C
HC
Hennies
Department of Dermatology and Venereology, Medical University Innsbruck, Innsbruck, Austria.|Center for Dermatogenetics, Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
R
R
Gruber
D000328:Adult; D055312:Cystatin A / Q000235:genetics*; D003937:Diagnosis, Differential; D004817:Epidermis / Q000473:pathology; D005533:Foot Dermatoses / Q000235:genetics / Q000473:pathology; D006229:Hand Dermatoses / Q000235:genetics / Q000473:pathology; D006720:Homozygote; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D009154:Mutation / Q000235:genetics*; D056770:Netherton Syndrome / Q000473:pathology; D012873:Skin Diseases, Genetic / Q000235:genetics* / Q000473:pathology
D055312:Cystatin A; C026407:CSTA protein, human