KLHL11 pathogenic variant in patients with lichen planus, abnormalities of the nails and tumour proneness

Targeted gene(s)/phenotype under study :

  • KLHL11 (OMIM 619078)

Abstract :

Lichen planus (LP) is a chronic inflammatory disorder affecting the skin, oral/genital mucosa, and scalp. LP has been associated with numerous systemic entities such as metabolic syndrome, diabetes mellitus, hypertension, thyroid dieseases, psychosomatic, chronic liver and gastrointestinal diseases.

We present a two-generation family with six people affected by LP in which dystrophic alterations in the nails are also associated and cancer of the tongue and other locations in two of them. Other relatives also died with cancer. The clinical findings segregate from parents to affected children suggesting an autosomal dominant inheritance. WES studies have been carried out in affected and healthy people in the family, identifying a variant in the KLHL11 gene that perfectly segregates with the clinical findings. The variant does not appear in the control population databases gnomADexomes, gnomADgenomas, Kaviar, 1000G, ESP). There are no disorders associated with this gene to date.

The KLHL11 gene belongs to the Kelch-like gene family (KLHL) and encodes a group of proteins that possess a BTB / POZ domain, a BACK domain, and five to six KELCH motifs. The full function of KLHL11 is not known, but several KLHL proteins bind to the E3 ligase cullin3 that are involved in ubiquitination. Other KLHL genes are responsible for Mendelian diseases and have been associated with cancer. KELCH-type proteins usually form homodimers, the detected variant in the present family could affect this interaction between KELCH monomers.

Coordinating clinicians/researchers:  Pablo Lapunzina

Institution :

INGEMM, Institute of Medical and Molecular Genetics

Hospital Universitario La Paz

Madrid-Spain

Contact :   plapunzina@ciberer.es      

Specific requirements beyond clinical data and genotype data sharing:

  • Re-analysis of DNA samples : Y
  • Resampling of patients : Y
  • Linked to a translational/basic research project? N

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