Hereditary benign intraepithelial dyskeratosis

Dithmar, Stefan; Stulting, R. Doyle; Grossniklaus, H. E.

doi:10.1007/s003470050335

Cited by 4 publications

(1 citation statement)

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“…Of the six reported affected probands that do not have Native American ancestry, four demonstrated conjunctival and corneal changes that were diagnosed by an ophthalmologist as consistent with HBID, with the diagnosis confirmed by histopathologic examination of conjunctival and corneal biopsy specimens. 1, 2, 13, 15 However, two of the reported probands demonstrated only oral manifestations characteristic of HBID, with minor actinic-appearing bulbar conjunctival changes in one proband and in 3 relatives of the other proband, consistent with pingueculae. These conjunctival lesions, photographs of which appear in the reports, appear to have been misinterpreted by the dermatologists, oral surgeons and pathologists who reported these cases as ocular manifestations of HBID.…”

Section: Discussionmentioning

confidence: 87%

Hereditary Benign Intraepithelial Dyskeratosis: Report of a Case and Re-examination of the Evidence for Locus Heterogeneity

Bui

Young

Frausto

et al. 2014

Ophthalmic Genetics

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Background Hereditary benign intraepithelial dyskeratosis (HBID) is a rare autosomal-dominant disorder of the conjunctiva and oral mucosa first described in and predominantly affecting descendents of Haliwa-Saponi Native Americans. We report a spontaneous case of histopathologically-confirmed HBID affecting an individual not of Native American ancestry. Materials and Methods Report of a case with histopathologic examination of an excised conjunctival specimen as well as molecular and cytogenetic analysis. Results A Caucasian boy with a history of oral lesions and conjunctival injection from birth developed bilateral corneal opacities at age 5 and underwent penetrating keratoplasty, with recurrence of the corneal opacification shortly after surgery. Examination of a conjuctival biopsy specimen revealed features consistent with HBID. Copy number variant (CNV) analysis revealed a de novo 4q35 duplication that overlapped the duplication previously associated with HBID, although no genes were identified in the common interval. NLRP1 gene sequencing failed to reveal a presumed pathogenic variant. Conclusions HBID may develop de novo in individuals who are not of Native American ancestry. The absence of coding regions in a duplicated region of 4q35 common to both the individual that we report and previously associated with HBID raises questions regarding the significance of this CNV in the pathogenesis of HBID.

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Section: Discussionmentioning

confidence: 87%

Hereditary Benign Intraepithelial Dyskeratosis: Report of a Case and Re-examination of the Evidence for Locus Heterogeneity

Bui

Young

Frausto

et al. 2014

Ophthalmic Genetics

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Conjunctival and Corneal Pathology

Keefe¹,

Milman²,

Rodrigues³

et al. 2008

Albert &Amp;amp;amp Jakobiec's Principles &Amp;amp;amp Practice of Ophthalmology

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Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis

Soler¹,

Tran-Viet

Galiacy

et al. 2013

J Med Genet

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Background Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology. Methods and results A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the proband’s mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure. Conclusions We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases.

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Hereditary benign intraepithelial dyskeratosis

Cited by 4 publications

References 0 publications

Hereditary Benign Intraepithelial Dyskeratosis: Report of a Case and Re-examination of the Evidence for Locus Heterogeneity

Hereditary Benign Intraepithelial Dyskeratosis: Report of a Case and Re-examination of the Evidence for Locus Heterogeneity

Conjunctival and Corneal Pathology

Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis

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