Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Art & Psychiatry
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Conference Oration
Conference Summary
Continuing Medical Education
Cosmetic Dermatology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
Editor Speaks
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Miscellaneous Letter
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News & Views
Observation Letter
Observation Letters
Original Article
Original Contributions
Pattern of Skin Diseases
Pediatric Dermatology
Pediatric Rounds
Presedential Address
Presidential Address
Presidents Remarks
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Study Letter
Study Letters
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapy Letter
Therapy Letters
View Point
What’s new in Dermatology
View/Download PDF

Translate this page into:

Letter to the Editor
doi: 10.4103/0378-6323.152298
PMID: 25751345

A recurrent R936X mutation of CYLD gene in a Chinese family with multiple familial trichoepithelioma

Qi-Guo Zhang, Yan-Hua Liang
 Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China

Correspondence Address:
Yan-Hua Liang
Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515
How to cite this article:
Zhang QG, Liang YH. A recurrent R936X mutation of CYLD gene in a Chinese family with multiple familial trichoepithelioma. Indian J Dermatol Venereol Leprol 2015;81:192-194
Copyright: (C)2015 Indian Journal of Dermatology, Venereology, and Leprology


Multiple familial trichoepithelioma (MFT; OMIM 601606) is an autosomal dominant skin disease characterized by the presence of many small benign tumors with pilar differentiation predominantly on the face. Mutations of the cylindromatosis (CYLD) gene have been first identified as the cause of multiple familial trichoepithelioma from Chinese Han populations in 2004. Loss of the deubiquitinating activity of CYLD protein is correlated with tumorigenesis. [1] Herein, we report a Chinese family with multiple familial trichoepithelioma with a recurrent mutation of CYLD, designated c. 2806C>T.

In this study, a large Chinese family consisting of six multiple familial trichoepithelioma patients in three generations was investigated [Figure - 1]a. The proband in the family was a 25-year-old female. She initially developed trichoepitheliomas at the age of 11 years. Dermatological examination showed numerous, dome-shaped, firm skin-colored papules and nodules involving the surface of nose, and the nasolabial folds [Figure - 1]b. Lesional skin biopsy from the proband revealed the typical histopathological characteristics of trichoepithelioma, such as palisade-like arrangement of small basaloid cells and multiple horn cysts with a fully keratinized center [Figure - 1]c. Blood samples were obtained from available family members and 100 unrelated controls.

Figure 1: The circles indicate females, the squares males. Blackened symbols represent affected individuals, open symbols represent unaffected individuals. The proband in the family (Individual III:2) is indicated by an arrow (a). Numerous trichoepitheliomas in the nasal region and nasolabial folds (b); Histology of trichoepithelioma excised from the face of the proband (H and E, 100×). Well-demarcated nodules consist of small basaloid cells that are arranged in a palisade-like pattern; multiple horn cysts with a fully keratinized center surrounded by basaloid cells lie free in the fibrous stroma. (c)

After informed consent and approval of human medical and ethics committee of Southern Medical University, genomic DNA was extracted from peripheral blood with a DNA isolation kit (Simgen Inc., Hangzhou, China). Polymerase chain reactions were performed as described in a previous study. [2] All polymerase chain reaction products were directly sequenced using dye terminator chemistry on an ABI 3730xl DNA Analyzer (Applied Biosystems, Foster City, CA). In addition, samples from 100 unrelated controls were sequenced to exclude the CYLD polymorphisms possibilities.

Sequence analysis identified a recurrent nonsense mutation, a change of C to T at nucleotide position 2806 in exon 20 in CYLD gene, resulting in a substitution of arginine (CGA) to terminal code (TGA) at position 936(p.R936X)  in the proband [Figure - 2]a. The same mutation was not found in 100 unrelated individuals [Figure - 2]b.

Figure 2: (a) Heterozygous c.2806(C>T) (p.R936X) mutation in exon 20 of the CYLD gene in proband of the pedigree. (b) Sequence of exon 20 of the CYLD gene in normal controls

The mutation c. 2806C>T (p.R936X) in CYLD has been reported in several studies. Bowen et al. identified a heterozygous R936X mutation in a Canadian woman with Brooke-Spiegler syndrome (BSS) who had cylindromas and trichoepitheliomas. [3] In a 73-year-old male with cylindromatosis and turban tumor syndrome, the heterozygous 2806C>T transition in the CYLD gene was identified. His two children, also carrying the mutation, had multiple familial trichoepithelioma without cylindromas. The findings suggested phenotypic variation of a single genetic defect. [4] The same nonsense mutation was identified in a woman of Czech ethnic background, who was one case from a series of 24 cases who developed malignant neoplasms arising in preexisting benign spiradenoma (n = 20), cylindroma (n = 2), or spiradenocylindroma (n = 2). [5] The development of malignant transformation in benign neoplasms in patients with p.R936X mutation of CYLD gene may be due to a second mutation in the tumor tissue or a homozygous c. 2806C>T mutation. Unfortunately, none of the previous studies were able to provide evidence of such mutation in patients who developed the malignant neoplasms.

In this study, we reported a large Chinese family with multiple familial trichoepithelioma and identified a recurrent nonsense mutation c. 2806C>T, leading to p.R936X in exon 20 of CYLD gene. This study expands the clinical heterogeneity of multiple familial trichoepitheliomas due to the same mutation (c. 2806C>T) in CYLD and contributes to enrichment of the database of the CYLD mutations underlying multiple familial trichoepitheliomas in the Chinese population. In the light of previous studies, our findings also suggest that though the mutation c. 2806C>T in CYLD mainly leads to a ′benign′ phenotype such as multiple familial trichoepithelioma Brooke-Spiegler syndrome, but may also result in a malignant phenotype.

Liang YH, Gao M, Sun LD, Liu LJ, Cui Y, Yang S, et al. Two novel CYLD gene mutations in Chinese families with trichoepithelioma and a literature review of 16 families with trichoepithelioma reported in China. Br J Dermatol 2005;153:1213-5.
[Google Scholar]
Zhang XJ, Liang YH, He PP, Yang S, Wang HY, Chen JJ, et al. Identification of the cylindromatosis tumor-suppressor gene responsible for multiple familial trichoepithelioma. J Invest Dermatol 2004;122:658-64.
[Google Scholar]
Bowen S, Gill M, Lee DA, Fisher G, Geronemus RG, Vazquez ME, et al. Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma: Lack of genotype-phenotype correlation. J Invest Dermatol 2005;124:919-20.
[Google Scholar]
Young AL, Kellermayer R, Szigeti R, Tészás A, Azmi S, Celebi JT. CYLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes. Clin Genet 2006;70:246-9.
[Google Scholar]
Kazakov DV, Zelger B, Rütten A, Vazmitel M, Spagnolo DV, Kacerovska D, et al. Morphologic diversity of malignant neoplasms arising in preexisting spiradenoma, cylindroma, and spiradenocylindroma based on the study of 24 cases, sporadic or occurring in the setting of Brooke-Spiegler syndrome. Am J Surg Pathol 2009;33:705-19.
[Google Scholar]

Fulltext Views

PDF downloads
Show Sections