Hereditary palmoplantar keratoderma – phenotypes and mutations in 64 patients

• Background: Hereditary palmoplantar keratodermas (PPK) represent a heterogeneous group of rare skin disorders with epidermal hyperkeratosis of the palms and soles, with occasional additional manifestations in other tissues. Mutations in at least 69 genes have been implicated in PPK, but further novel candidate genes and mutations are still to be found. Objectives: To identify mutations underlying PPK in a cohort of 64 patients. Methods: DNA of 48 patients was analysed on a custom-designed in-house panel for 35 PPK genes, and 16 patients were investigated by a diagnostic genetic laboratory either by whole-exome sequencing, gene panels or targeted single-gene sequencing. Results: Of the 64 PPK patients, 32 had diffuse (50%), 19 focal (30%) and 13 punctate (20%) PPK. None had striate PPK. Pathogenic mutations in altogether five genes were identified in 31 of 64 (48%) patients, the majority (22/31) with diffuse PPK. Of them, 11 had a mutation in AQP5, five in SERPINB7, four in KRT9 and two in SLURP1. AAGAB mutations were found in nine punctate PPK patients. New mutations were identified in KRT9 and AAGAB. No pathogenic mutations were detected in focal PPK. Variants of uncertain significance (VUS) in PPK-associated and other genes were observed in 21 patients that might explain their PPK. No suggestive pathogenic variants were found for 12 patients. Conclusions: Diffuse PPK was the most common (50%) and striate PPK was not observed. We identified pathogenic mutations in 48% of our PPK patients, mainly in five genes: AQP5, AAGAB, KRT9, SERPINB7 and SLURP1. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

aquaporin 5

cytokeratin 9

AAGAB protein

human

Ly antigen

serine proteinase inhibitor

SERPINB7 protein

human

SLURP1 protein

human

urokinase

vesicular transport adaptor protein

AAGAB gene

adolescent

adult

AQP5 gene

Article

child

diffuse palmoplantar keratoderma

disease classification

female

focal palmoplantar keratoderma

gene

gene mutation

genetic disorder

hereditary palmoplantar keratoderma

human

KRT9 gene

major clinical study

male

palmoplantar keratoderma

phenotype

punctate palmoplantar keratoderma

SERPINB7 gene

SLURP1 gene

whole exome sequencing

genetics

mutation

pedigree

Adaptor Proteins

Vesicular Transport

Antigens

Ly

Humans

Keratoderma

Palmoplantar

Keratoderma

Palmoplantar

Diffuse

Serpins

Urokinase-Type Plasminogen Activator

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)