CEDNIK syndrome results from loss-of-function mutations in SNAP29

D Fuchs-Telem; H Stewart; D Rapaport; J Nousbeck; A Gat; M Gini; Y Lugassy; S Emmert; K Eckl; H C Hennies; O Sarig; D Goldsher; B Meilik; A Ishida-Yamamoto; M Horowitz; E Sprecher

doi:10.1111/j.1365-2133.2010.10133.x

CEDNIK syndrome results from loss-of-function mutations in SNAP29

D Fuchs-Telem, H Stewart, D Rapaport, J Nousbeck, A Gat, M Gini, Y Lugassy, S Emmert, K Eckl, H C Hennies, O Sarig, D Goldsher, B Meilik, A Ishida-Yamamoto, M Horowitz, E Sprecher

Research output: Contribution to journal › Article › peer-review

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Abstract

BACKGROUND: CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis and keratoderma) syndrome is a rare genodermatosis which was shown 5 years ago in one family to be associated with a loss-of-function mutation in SNAP29, encoding a member of the SNARE family of proteins. Decrease in SNAP29 expression was found to result in abnormal lamellar granule maturation leading to aberrant epidermal differentiation and ichthyosis.

OBJECTIVES: To delineate the molecular consequences of disease-causing mutations in SNAP29.

METHODS: We used direct sequencing, in vitro mutagenesis and three-dimensional organotypic cell cultures.

RESULTS: We identified a novel homozygous insertion in SNAP29 (c.486insA) in two sibs presenting with ichthyosis and dysgenesis of the corpus callosum. In vitro transfection experiments indicated that this mutation results in SNAP29 loss-of-function. Further substantiating this notion, we could replicate histological features typical for CEDNIK syndrome in three-dimensional primary human keratinocyte organotypic cell cultures downregulated for SNAP29.

CONCLUSIONS: The identification of a second mutation in SNAP29 in the present study definitely establishes a causal relationship between defective function of SNAP29 and the pleiotropic manifestations of CEDNIK syndrome. Our present and previous data position SNAP29 as an essential component of the epidermal differentiation machinery.

Original language	English
Pages (from-to)	610-616
Number of pages	7
Journal	British Journal of Dermatology
Volume	164
Issue number	3
DOIs	https://doi.org/10.1111/j.1365-2133.2010.10133.x
Publication status	Published - Mar 2011
Externally published	Yes

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10.1111/j.1365-2133.2010.10133.x

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Fuchs-Telem, D., Stewart, H., Rapaport, D., Nousbeck, J., Gat, A., Gini, M., Lugassy, Y., Emmert, S., Eckl, K., Hennies, H. C., Sarig, O., Goldsher, D., Meilik, B., Ishida-Yamamoto, A., Horowitz, M., & Sprecher, E. (2011). CEDNIK syndrome results from loss-of-function mutations in SNAP29. British Journal of Dermatology, 164(3), 610-616. https://doi.org/10.1111/j.1365-2133.2010.10133.x

@article{24d8a1e4b55647bdae5af37aa46c2f61,

title = "CEDNIK syndrome results from loss-of-function mutations in SNAP29",

abstract = "BACKGROUND: CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis and keratoderma) syndrome is a rare genodermatosis which was shown 5 years ago in one family to be associated with a loss-of-function mutation in SNAP29, encoding a member of the SNARE family of proteins. Decrease in SNAP29 expression was found to result in abnormal lamellar granule maturation leading to aberrant epidermal differentiation and ichthyosis.OBJECTIVES: To delineate the molecular consequences of disease-causing mutations in SNAP29.METHODS: We used direct sequencing, in vitro mutagenesis and three-dimensional organotypic cell cultures.RESULTS: We identified a novel homozygous insertion in SNAP29 (c.486insA) in two sibs presenting with ichthyosis and dysgenesis of the corpus callosum. In vitro transfection experiments indicated that this mutation results in SNAP29 loss-of-function. Further substantiating this notion, we could replicate histological features typical for CEDNIK syndrome in three-dimensional primary human keratinocyte organotypic cell cultures downregulated for SNAP29.CONCLUSIONS: The identification of a second mutation in SNAP29 in the present study definitely establishes a causal relationship between defective function of SNAP29 and the pleiotropic manifestations of CEDNIK syndrome. Our present and previous data position SNAP29 as an essential component of the epidermal differentiation machinery.",

keywords = "Blotting, Western, Cells, Cultured, Female, Humans, Infant, Keratoderma, Palmoplantar, Male, Mutation, Neurocutaneous Syndromes, Qb-SNARE Proteins, Qc-SNARE Proteins, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Case Reports, Journal Article, Research Support, Non-U.S. Gov't",

author = "D Fuchs-Telem and H Stewart and D Rapaport and J Nousbeck and A Gat and M Gini and Y Lugassy and S Emmert and K Eckl and Hennies, \{H C\} and O Sarig and D Goldsher and B Meilik and A Ishida-Yamamoto and M Horowitz and E Sprecher",

note = "{\textcopyright} 2011 The Authors. BJD {\textcopyright} 2011 British Association of Dermatologists.",

year = "2011",

month = mar,

doi = "10.1111/j.1365-2133.2010.10133.x",

language = "English",

volume = "164",

pages = "610--616",

journal = "British Journal of Dermatology",

issn = "0007-0963",

publisher = "Oxford University Press",

number = "3",

}

Fuchs-Telem, D, Stewart, H, Rapaport, D, Nousbeck, J, Gat, A, Gini, M, Lugassy, Y, Emmert, S, Eckl, K, Hennies, HC, Sarig, O, Goldsher, D, Meilik, B, Ishida-Yamamoto, A, Horowitz, M & Sprecher, E 2011, 'CEDNIK syndrome results from loss-of-function mutations in SNAP29', British Journal of Dermatology, vol. 164, no. 3, pp. 610-616. https://doi.org/10.1111/j.1365-2133.2010.10133.x

TY - JOUR

T1 - CEDNIK syndrome results from loss-of-function mutations in SNAP29

AU - Fuchs-Telem, D

AU - Stewart, H

AU - Rapaport, D

AU - Nousbeck, J

AU - Gat, A

AU - Gini, M

AU - Lugassy, Y

AU - Emmert, S

AU - Eckl, K

AU - Hennies, H C

AU - Sarig, O

AU - Goldsher, D

AU - Meilik, B

AU - Ishida-Yamamoto, A

AU - Horowitz, M

AU - Sprecher, E

PY - 2011/3

Y1 - 2011/3

N2 - BACKGROUND: CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis and keratoderma) syndrome is a rare genodermatosis which was shown 5 years ago in one family to be associated with a loss-of-function mutation in SNAP29, encoding a member of the SNARE family of proteins. Decrease in SNAP29 expression was found to result in abnormal lamellar granule maturation leading to aberrant epidermal differentiation and ichthyosis.OBJECTIVES: To delineate the molecular consequences of disease-causing mutations in SNAP29.METHODS: We used direct sequencing, in vitro mutagenesis and three-dimensional organotypic cell cultures.RESULTS: We identified a novel homozygous insertion in SNAP29 (c.486insA) in two sibs presenting with ichthyosis and dysgenesis of the corpus callosum. In vitro transfection experiments indicated that this mutation results in SNAP29 loss-of-function. Further substantiating this notion, we could replicate histological features typical for CEDNIK syndrome in three-dimensional primary human keratinocyte organotypic cell cultures downregulated for SNAP29.CONCLUSIONS: The identification of a second mutation in SNAP29 in the present study definitely establishes a causal relationship between defective function of SNAP29 and the pleiotropic manifestations of CEDNIK syndrome. Our present and previous data position SNAP29 as an essential component of the epidermal differentiation machinery.

AB - BACKGROUND: CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis and keratoderma) syndrome is a rare genodermatosis which was shown 5 years ago in one family to be associated with a loss-of-function mutation in SNAP29, encoding a member of the SNARE family of proteins. Decrease in SNAP29 expression was found to result in abnormal lamellar granule maturation leading to aberrant epidermal differentiation and ichthyosis.OBJECTIVES: To delineate the molecular consequences of disease-causing mutations in SNAP29.METHODS: We used direct sequencing, in vitro mutagenesis and three-dimensional organotypic cell cultures.RESULTS: We identified a novel homozygous insertion in SNAP29 (c.486insA) in two sibs presenting with ichthyosis and dysgenesis of the corpus callosum. In vitro transfection experiments indicated that this mutation results in SNAP29 loss-of-function. Further substantiating this notion, we could replicate histological features typical for CEDNIK syndrome in three-dimensional primary human keratinocyte organotypic cell cultures downregulated for SNAP29.CONCLUSIONS: The identification of a second mutation in SNAP29 in the present study definitely establishes a causal relationship between defective function of SNAP29 and the pleiotropic manifestations of CEDNIK syndrome. Our present and previous data position SNAP29 as an essential component of the epidermal differentiation machinery.

KW - Blotting, Western

KW - Cells, Cultured

KW - Female

KW - Humans

KW - Infant

KW - Keratoderma, Palmoplantar

KW - Male

KW - Mutation

KW - Neurocutaneous Syndromes

KW - Qb-SNARE Proteins

KW - Qc-SNARE Proteins

KW - RNA, Messenger

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Sequence Analysis, DNA

KW - Case Reports

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/j.1365-2133.2010.10133.x

DO - 10.1111/j.1365-2133.2010.10133.x

M3 - Article

C2 - 21073448

SN - 0007-0963

VL - 164

SP - 610

EP - 616

JO - British Journal of Dermatology

JF - British Journal of Dermatology

IS - 3

ER -

CEDNIK syndrome results from loss-of-function mutations in SNAP29

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