Genetic Testing in CYLD Cutaneous Syndrome: An Update

Nagy, Nikoletta; Dubois, Anna; Széll, Márta; Rajan, Neil

doi:10.2147/tacg.s288274

Cited by 9 publications

(8 citation statements)

References 110 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CYLD gene contains 20 exons encoding a deubiquitinating enzyme that functions as a tumor suppressor gene within the nuclear factor kappa-light-chain-enhancer of activated B cells pathway. 3 A recent study by Nagy et al 4 summarized the 107 germline variants that have been published to date associated with CYLD cutaneous tumor syndromes. The vast majority (99%) of mutations have been found within exons 9 to 20, with most of these occurring in exons 16, 17, and 20 ( Table II ).…”

Section: Discussionmentioning

confidence: 99%

“…The vast majority (99%) of mutations have been found within exons 9 to 20, with most of these occurring in exons 16, 17, and 20 ( Table II ). 4 Little correlation exists between CYLD genotype and the cutaneous syndrome that the patient develops, 5 and recent evidence indicates that expression of genes other than CYLD , such as DKK2, may influence whether tumors differentiate toward cylindromas or spiradenomas. 6 …”

Section: Discussionmentioning

confidence: 99%

“… 4 Little correlation exists between CYLD genotype and the cutaneous syndrome that the patient develops, 5 and recent evidence indicates that expression of genes other than CYLD , such as DKK2, may influence whether tumors differentiate toward cylindromas or spiradenomas. 6 …”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Case report of syndromic multiple spiradenomas due to biallelic functional loss of CYLD

et al. 2022

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Case report of syndromic multiple spiradenomas due to biallelic functional loss of CYLD

et al. 2022

View full text Add to dashboard Cite

“…However, this may depend on the incomplete sensitivity of the molecular techniques employed, or on the presence of mosaics. Interestingly, large deletions that are usually missed by traditional sequencing methods have rarely been reported in BSS [15]; in addition, deep intronic changes, or variations in the promoter region, are usually not covered by standard analyses [16,17].…”

Section: Database Researchmentioning

confidence: 99%

A Misdiagnosed Familiar Brooke–Spiegler Syndrome: Case Report and Review of the Literature

Brambullo,

De Lazzari,

Franchi

et al. 2024

JCM

View full text Add to dashboard Cite

Aim of the report: Brooke–Spiegler syndrome (BSS) is a rare autosomal dominant disease characterized by the growth of cylindromas, spiradenomas, trichoepitheliomas, or their combination. These neoplasms usually begin in the second decade and progressively increase in number and size over the years. Diagnosis necessitates consideration of family history, clinical examination, histological findings, and genetic analysis. The aim of this paper is to explore the clinical overlap between Brooke–Spiegler syndrome (BSS) and neurofibromatosis type 1 (NF1). We aim to highlight the challenges associated with their differential diagnosis and emphasize the lack of standardized diagnostic criteria and treatment approaches. Case presentation: Hereby, we introduce the case of a 28-year-old male referred for suspicion of neurofibromatosis type 1 (NF1) who initially declined the recommended surgical excision for a scalp mass. After four years, he returned with larger masses of the scalp, and underwent excision of multiple masses, revealing cylindromas, spiradenomas, and spiradenocylindromas. Family history reported similar tumors in his father, who was also diagnosed with NF1 for the presence of multiple subcutaneous lesions on the scalp. Clinical overlap led to a genetic consultation, but testing for CYLD mutations yielded no significant variations. Despite this, the strong family history and consistent findings led to a revised diagnosis of Brooke–Spiegler syndrome, correcting the initial misdiagnosis of NF1 syndrome. Conclusions: Thanks to the evolving landscape of BSS research over the past two decades, its molecular underpinnings, clinical presentation, and histopathological features are now clearer. However, a thorough family history assessment is mandatory when BSS is suspected. It is our belief that a multidisciplinary approach and cooperation between specialists are essential when dealing with BSS. By sharing this case, we hope to underscore the importance of considering BSS as a differential diagnosis, especially in cases with atypical presentations or overlapping features with other syndromes like NF1.

show abstract

“…Protein ubiquitination is a reversible process, wherein deubiquitinating enzymes can cleave ubiquitin from its protein substrates [ 13 ]. Cylindromatosis (CYLD) gene is located on chromosome 16q12-13, and its encoded protein CYLD is considered to be a key regulator of inflammatory response [ 14 ]. CYLD exhibits deubiquitinase activity and plays an important role in multiple signaling pathways [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

CYLD alleviates NLRP3 inflammasome-mediated pyroptosis in osteoporosis by deubiquitinating WNK1

Jiang,

Cai,

Cheng

et al. 2024

J Orthop Surg Res

View full text Add to dashboard Cite

Background Osteoporosis (OP) is the result of bone mass reduction and bone structure disorder. Bone marrow mesenchymal stem cells (BMSCs) are the main source of osteogenic precursor cells involved in adult bone remodeling. The involvement of the deubiquitinating enzyme CYLD in OP has recently been discovered. However, the detailed role and mechanism of CYLD remain unknown. Methods The OP mouse model was established by performing ovariectomy (OVX) on mice. Hematoxylin and eosin staining, Masson and Immunohistochemical staining were used to assess pathologic changes. Real-time quantitative PCR, Western blot, and immunofluorescence were employed to assess the expression levels of CYLD, WNK1, NLRP3 and osteogenesis-related molecules. The binding relationship between CYLD and WNK1 was validated through a co-immunoprecipitation assay. The osteogenic capacity of BMSCs was determined using Alkaline phosphatase (ALP) and alizarin red staining (ARS). Protein ubiquitination was evaluated by a ubiquitination assay. Results The levels of both CYLD and WNK1 were decreased in bone tissues and BMSCs of OVX mice. Overexpression of CYLD or WNK1 induced osteogenic differentiation in BMSCs. Additionally, NLRP3 inflammation was activated in OVX mice, but its activation was attenuated upon overexpression of CYLD or WNK1. CYLD was observed to reduce the ubiquitination of WNK1, thereby enhancing its protein stability and leading to the inactivation of NLRP3 inflammation. However, the protective effects of CYLD on osteogenic differentiation and NLRP3 inflammation inactivation were diminished upon silencing of WNK1. Conclusion CYLD mitigates NLRP3 inflammasome-triggered pyroptosis in osteoporosis through its deubiquitination of WNK1.

show abstract

Genetic Testing in CYLD Cutaneous Syndrome: An Update

Cited by 9 publications

References 110 publications

Case report of syndromic multiple spiradenomas due to biallelic functional loss of CYLD

Case report of syndromic multiple spiradenomas due to biallelic functional loss of CYLD

A Misdiagnosed Familiar Brooke–Spiegler Syndrome: Case Report and Review of the Literature

CYLD alleviates NLRP3 inflammasome-mediated pyroptosis in osteoporosis by deubiquitinating WNK1

Contact Info

Product

Resources

About