Morphological alterations in two siblings with autosomal recessive congenital ichthyosis associated with CYP4F22 mutations

R. Gruber, G. Rainer, A. Weiss, A. Udvardi, Holger Thiele, Katja Martina Eckl, R. Schupart, Peter Nürnberg, Johannes Zschocke, Matthias Schmuth, B. Volc-platzer, Hans Hennies

Research output: Contribution to journalArticle

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Abstract

Autosomal recessive congenital ichthyosis (ARCI) caused by mutations in CYP4F22 is very rare. CyP4F22, a protein of the cytochrome-P450 family 4, encodes an epidermal ω-hydroxylase decisive in the formation of acylceramides, which is hypothesized to be crucial for skin-barrier function. We report a girl with consanguineous parents presenting as collodion baby with contractures of the great joints and palmoplantar hyperlinearity. In the course of the disease she developed fine scaling of the skin with erythroderma, the latter disappearing until the age of 6 months. Her sister showed a generalized fine-scaling phenotype, and, interestingly, was born without a collodion membrane. The analysis of all known candidate genes for ARCI in parallel with a next-generation sequencing approach using a newly designed dermatogenetics gene panel revealed a previously unknown homozygous splice-site mutation c.549+5G>C in CYP4F22 in both girls, confirming the diagnosis of ARCI. Ultrastructural analysis by transmission electron microscopy in both patients showed epidermal hyperplasia, orthohyperkeratosis with persistence of corneodesmosomes into the outer stratum corneum layers, fragmented and disorganized lamellar lipid bilayers, which could be ascribed to inhomogeneous lamellar body secretion, as well as lamellar body and lipid entombment in the corneocytes. These findings correlated with increased transepidermal water loss on the functional level. For the first time, we report a collodion baby phenotype and epidermal barrier impairment in CyP4F22-deficient epidermis at both the ultrastructural and functional level, and corroborate the importance of CyP4F22 for epidermal maturation and barrier function.
LanguageEnglish
Pages1068-1073
Number of pages6
JournalBritish Journal of Dermatology
Volume176
Issue number4
Early online date17 Jan 2017
DOIs
Publication statusPublished - Apr 2017

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Ichthyosis
Collodion
Siblings
Mutation
Cytochrome P-450 CYP4A
Exfoliative Dermatitis
Phenotype
Recessive Genes
Skin
Lipid Bilayers
Contracture
Transmission Electron Microscopy
Epidermis
Cornea
Hyperplasia
Joints
Parents
Lipids
Membranes
Water

Cite this

Gruber, R. ; Rainer, G. ; Weiss, A. ; Udvardi, A. ; Thiele, Holger ; Eckl, Katja Martina ; Schupart, R. ; Nürnberg, Peter ; Zschocke, Johannes ; Schmuth, Matthias ; Volc-platzer, B. ; Hennies, Hans. / Morphological alterations in two siblings with autosomal recessive congenital ichthyosis associated with CYP4F22 mutations. In: British Journal of Dermatology. 2017 ; Vol. 176, No. 4. pp. 1068-1073.
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abstract = "Autosomal recessive congenital ichthyosis (ARCI) caused by mutations in CYP4F22 is very rare. CyP4F22, a protein of the cytochrome-P450 family 4, encodes an epidermal ω-hydroxylase decisive in the formation of acylceramides, which is hypothesized to be crucial for skin-barrier function. We report a girl with consanguineous parents presenting as collodion baby with contractures of the great joints and palmoplantar hyperlinearity. In the course of the disease she developed fine scaling of the skin with erythroderma, the latter disappearing until the age of 6 months. Her sister showed a generalized fine-scaling phenotype, and, interestingly, was born without a collodion membrane. The analysis of all known candidate genes for ARCI in parallel with a next-generation sequencing approach using a newly designed dermatogenetics gene panel revealed a previously unknown homozygous splice-site mutation c.549+5G>C in CYP4F22 in both girls, confirming the diagnosis of ARCI. Ultrastructural analysis by transmission electron microscopy in both patients showed epidermal hyperplasia, orthohyperkeratosis with persistence of corneodesmosomes into the outer stratum corneum layers, fragmented and disorganized lamellar lipid bilayers, which could be ascribed to inhomogeneous lamellar body secretion, as well as lamellar body and lipid entombment in the corneocytes. These findings correlated with increased transepidermal water loss on the functional level. For the first time, we report a collodion baby phenotype and epidermal barrier impairment in CyP4F22-deficient epidermis at both the ultrastructural and functional level, and corroborate the importance of CyP4F22 for epidermal maturation and barrier function.",
author = "R. Gruber and G. Rainer and A. Weiss and A. Udvardi and Holger Thiele and Eckl, {Katja Martina} and R. Schupart and Peter N{\"u}rnberg and Johannes Zschocke and Matthias Schmuth and B. Volc-platzer and Hans Hennies",
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doi = "10.1111/bjd.14860",
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Gruber, R, Rainer, G, Weiss, A, Udvardi, A, Thiele, H, Eckl, KM, Schupart, R, Nürnberg, P, Zschocke, J, Schmuth, M, Volc-platzer, B & Hennies, H 2017, 'Morphological alterations in two siblings with autosomal recessive congenital ichthyosis associated with CYP4F22 mutations', British Journal of Dermatology, vol. 176, no. 4, pp. 1068-1073. https://doi.org/10.1111/bjd.14860

Morphological alterations in two siblings with autosomal recessive congenital ichthyosis associated with CYP4F22 mutations. / Gruber, R.; Rainer, G.; Weiss, A.; Udvardi, A.; Thiele, Holger; Eckl, Katja Martina; Schupart, R.; Nürnberg, Peter; Zschocke, Johannes; Schmuth, Matthias; Volc-platzer, B.; Hennies, Hans.

In: British Journal of Dermatology, Vol. 176, No. 4, 04.2017, p. 1068-1073.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Morphological alterations in two siblings with autosomal recessive congenital ichthyosis associated with CYP4F22 mutations

AU - Gruber, R.

AU - Rainer, G.

AU - Weiss, A.

AU - Udvardi, A.

AU - Thiele, Holger

AU - Eckl, Katja Martina

AU - Schupart, R.

AU - Nürnberg, Peter

AU - Zschocke, Johannes

AU - Schmuth, Matthias

AU - Volc-platzer, B.

AU - Hennies, Hans

PY - 2017/4

Y1 - 2017/4

N2 - Autosomal recessive congenital ichthyosis (ARCI) caused by mutations in CYP4F22 is very rare. CyP4F22, a protein of the cytochrome-P450 family 4, encodes an epidermal ω-hydroxylase decisive in the formation of acylceramides, which is hypothesized to be crucial for skin-barrier function. We report a girl with consanguineous parents presenting as collodion baby with contractures of the great joints and palmoplantar hyperlinearity. In the course of the disease she developed fine scaling of the skin with erythroderma, the latter disappearing until the age of 6 months. Her sister showed a generalized fine-scaling phenotype, and, interestingly, was born without a collodion membrane. The analysis of all known candidate genes for ARCI in parallel with a next-generation sequencing approach using a newly designed dermatogenetics gene panel revealed a previously unknown homozygous splice-site mutation c.549+5G>C in CYP4F22 in both girls, confirming the diagnosis of ARCI. Ultrastructural analysis by transmission electron microscopy in both patients showed epidermal hyperplasia, orthohyperkeratosis with persistence of corneodesmosomes into the outer stratum corneum layers, fragmented and disorganized lamellar lipid bilayers, which could be ascribed to inhomogeneous lamellar body secretion, as well as lamellar body and lipid entombment in the corneocytes. These findings correlated with increased transepidermal water loss on the functional level. For the first time, we report a collodion baby phenotype and epidermal barrier impairment in CyP4F22-deficient epidermis at both the ultrastructural and functional level, and corroborate the importance of CyP4F22 for epidermal maturation and barrier function.

AB - Autosomal recessive congenital ichthyosis (ARCI) caused by mutations in CYP4F22 is very rare. CyP4F22, a protein of the cytochrome-P450 family 4, encodes an epidermal ω-hydroxylase decisive in the formation of acylceramides, which is hypothesized to be crucial for skin-barrier function. We report a girl with consanguineous parents presenting as collodion baby with contractures of the great joints and palmoplantar hyperlinearity. In the course of the disease she developed fine scaling of the skin with erythroderma, the latter disappearing until the age of 6 months. Her sister showed a generalized fine-scaling phenotype, and, interestingly, was born without a collodion membrane. The analysis of all known candidate genes for ARCI in parallel with a next-generation sequencing approach using a newly designed dermatogenetics gene panel revealed a previously unknown homozygous splice-site mutation c.549+5G>C in CYP4F22 in both girls, confirming the diagnosis of ARCI. Ultrastructural analysis by transmission electron microscopy in both patients showed epidermal hyperplasia, orthohyperkeratosis with persistence of corneodesmosomes into the outer stratum corneum layers, fragmented and disorganized lamellar lipid bilayers, which could be ascribed to inhomogeneous lamellar body secretion, as well as lamellar body and lipid entombment in the corneocytes. These findings correlated with increased transepidermal water loss on the functional level. For the first time, we report a collodion baby phenotype and epidermal barrier impairment in CyP4F22-deficient epidermis at both the ultrastructural and functional level, and corroborate the importance of CyP4F22 for epidermal maturation and barrier function.

U2 - 10.1111/bjd.14860

DO - 10.1111/bjd.14860

M3 - Article

VL - 176

SP - 1068

EP - 1073

JO - British Journal of Dermatology

T2 - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

IS - 4

ER -