Phenotype-genotype correlations for clinical variants caused by CYLD mutations

Area of Science:

• Genetics
• Dermatology
• Molecular Biology

Background:

• Brooke-Spiegler syndrome (BSS) is an autosomal dominant disorder characterized by skin appendageal neoplasms.
• Mutations in the cylindromatosis (CYLD) gene cause BSS, familial cylindromatosis (FC), and multiple familial trichoepithelioma type 1 (MFT1).
• The CYLD gene encodes a deubiquitinase enzyme, and 95 disease-causing mutations have been identified previously.

Purpose of the Study:

• To summarize CYLD gene mutations found in Hungarian patients.
• To review previously published CYLD gene mutations.
• To analyze genotype-phenotype correlations in BSS, FC, and MFT1.

Main Methods:

• Literature review of published CYLD gene mutations.
• Analysis of mutations identified in Hungarian patients.
• Correlation analysis between CYLD genotypes and clinical phenotypes.

Main Results:

• The majority of CYLD mutations are frameshift (48%), nonsense (27%), missense (12%), and splice-site (11%).
• Most mutations are located in exons 9-20 of the CYLD gene.
• Significant genotype-phenotype correlations were observed for BSS, FC, and MFT1.

Conclusions:

• Understanding genotype-phenotype correlations is crucial for diagnosing rare monogenic skin diseases like BSS.
• Characterizing these correlations can advance the understanding of disease mechanisms.
• This knowledge may contribute to developing future therapeutic strategies for these conditions.