Novel autosomal dominant mutation in loricrin presenting as prominent ichthyosis

Pöhler, Elizabeth; Cunningham, F. J.; Sandilands, Aileen; Callebaut, Christian; Digby, S.; McMillan, James R.; Aristodemou, Sophia; McGrath, John A.; Smith, Frances J.D.; McLean, William; Munro, Colin S.; Zamiri, M.

doi:10.1111/bjd.13895

Cited by 16 publications

(9 citation statements)

References 16 publications

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“…Common clinical features include palmoplantar keratoderma – usually with a honeycomb pattern – and generalized ichthyosis. Other features, such as knuckle pads, pseudoainhum/hyperconstricting bands with autoamputation of digits, and collodion babies, have been reported to varying degrees . Histopathology sometimes shows pathognomonic findings such as hyperkeratosis with round retained nuclei and hypergranulosis.…”

Section: Isolated Palmoplantar Keratodermasmentioning

confidence: 99%

Palmoplantar keratodermas: clinical and genetic aspects

Has

Technau‐Hafsi

2016

J Deutsche Derma Gesell

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Summary Palmoplantar keratodermas comprise a diverse group of acquired and hereditary disorders marked by excessive thickening of the epidermis of palms and soles. Early onset and positive family history suggest a genetic cause. While hereditary forms of palmoplantar keratoderma (PPK) may represent the sole or dominant clinical feature, they may also be associated with other ectodermal defects or extracutaneous manifestations. In recent years, much progress has been made in deciphering the genetic basis of PPK, which has led to the emergence of new disorders and syndromes. The elucidation of disease mechanisms has opened new avenues for specific therapies, increasingly sparking interest in this field. Given the high heterogeneity with respect to clinical features, genetic defects, and disease mechanisms, the classification of PPK is based on various criteria. These include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis. Though not always feasible, the clinical distinction of various PPK entities is based on fine‐tuned criteria or clues. Remarkably, apparently distinct disorders have been shown to be allelic, as they are caused by mutations in the same gene. By contrast, similar clinical pictures may result from mutations in different genes. Because of this complexity, mutation analysis is required to determine the precise type of PPK. The best‐defined entities are described in this review.

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Section: Isolated Palmoplantar Keratodermasmentioning

confidence: 99%

Palmoplantar keratodermas: clinical and genetic aspects

Has

Technau‐Hafsi

2016

J Deutsche Derma Gesell

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“…In support of this, recent studies have suggested that the accumulation of genetic mutations is directly associated with the frequency of cell division, which obviously increases with age (Tomasetti & Vogelstein, 2015), and that aging Drosophila intestinal SCs experience frequent somatic recombination that results in clonal mosaicism (Siudeja et al, 2015). Second, LK patients do not always present with erythema or erythematous plaques (Ishida-Yamamoto, 2003; Pohler et al, 2015); consequently, revertant skin spots easily escape patients’ and even clinicians’ attention. Indeed, in our cases, revertant skin spots were clinically detected as well-demarcated, round or oval-shaped islands of unaffected skin appearing on an erythematous background of affected skin (Figs 1I and 3E).…”

Section: Discussionmentioning

confidence: 99%

“…The late epidermal differentiation marker loricrin is the major component of the cornified envelope, a highly insoluble and robust structure that is formed beneath the cell membrane of keratinocytes during terminal differentiation and provides the vital physical barrier to the skin (Ishida-Yamamoto, 2003). LK is clinically characterized by defective skin barrier phenotypes, such as palmoplantar keratoderma (thickening of the skin on the palms and soles; PPK) and generalized ichthyosis (dry, thickened, and scaly skin), with or without varying degrees of constricted digits, erythematous plaques, and/or erythroderma (generalized red skin) (Maestrini et al, 1996; Ishida-Yamamoto et al, 1997; Ishida-Yamamoto, 2003; Pohler et al, 2015). Notably, all LOR mutations reported to date cause a frameshift and replace the glycine-rich C-terminus of the 315-amino-acid wild-type loricrin protein with a highly arginine-rich nuclear localization signal sequence (Maestrini et al, 1996; Ishida-Yamamoto et al, 1997; Ishida-Yamamoto, 2003; Pohler et al, 2015; Khalil et al, 2017), leading to the accumulation of mutant loricrin in the nucleolus of affected keratinocytes (Ishida-Yamamoto, 2003).…”

Section: Introductionmentioning

confidence: 99%

Somatic recombination underlies frequent revertant mosaicism in loricrin keratoderma

et al. 2019

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“…Die gemeinsamen klinischen Merkmale sind Palmoplantarkeratose, in der Regel mit honigwabenförmiger Struktur, und generalisierte Ichthyose. Weitere Merkmale, darunter Knöchelpolster, Pseudoainhums/furchenartige Einschnürungen mit Autoamputation der Finger und Kollodiumbabys, werden mit wechselnder Häufigkeit beobachtet . In der Histopathologie zeigen sich gelegentlich pathognomonische Merkmale einer Hyperkeratose wie runde Zellkernreste zusammen mit Hypergranulose.…”

Section: Isolierte Palmoplantarkeratosenunclassified

Keratosis palmoplantaris: klinische und genetische Aspekte

Has

Technau‐Hafsi

2016

J Deutsche Derma Gesell

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Zu den Palmoplantarkeratosen (PPK) gehören verschiedene erworbene und angeborene Störungen, die durch übermäßige Verdickung der Epidermis an Handflächen und Fußsohlen gekennzeichnet sind. Ein früher Ausbruch und eine positive Familienanamnese weisen auf eine genetische Ursache der PPK hin. Eine angeborene PPK kann das einzige oder das dominante klinische Merkmal darstellen oder sie kann von anderen ektodermalen Dysplasien oder extrakutanen Symptomen begleitet sein. In der letzten Zeit wurden bei der Entschlüsselung der genetischen Grundlagen der PPK deutliche Fortschritte erzielt und neue Störungen und Syndrome sind bekannt geworden. Die Aufklärung der Krankheitsmechanismen öffnet neue Wege für spezifische Therapien und macht dieses Gebiet immer interessanter. Wegen der starken Heterogenität der klinischen Merkmale, genetischen Defekte und Krankheitsmechanismen können PPK auf der Grundlage unterschiedlicher Kriterien klassifiziert werden. Dazu gehören das Ausmaß der Krankheitsmanifestationen, die Morphologie der befallenen palmoplantaren Hautbereiche, das Vererbungsmuster oder die molekulare Pathogenese. Die klinische Differenzierung zwischen den PPK-Entitäten stützt sich auf subtile Kriterien oder Anzeichen und ist nicht immer möglich. Interessanterweise haben sich scheinbar unterschiedliche Erkrankungen als allelisch erwiesen, werden also durch Mutationen im selben Gen ausgelöst. Andererseits können ähnliche Krankheitsbilder durch Mutationen in verschiedenen Genen verursacht sein. Aufgrund dieser Komplexität muss der genaue Typ der PPK durch Mutationsanalyse bestimmt werden. Die am besten definierten Entitäten werden in diesem Übersichtsartikel beschrieben.

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Novel autosomal dominant mutation in loricrin presenting as prominent ichthyosis

Cited by 16 publications

References 16 publications

Palmoplantar keratodermas: clinical and genetic aspects

Palmoplantar keratodermas: clinical and genetic aspects

Somatic recombination underlies frequent revertant mosaicism in loricrin keratoderma

Keratosis palmoplantaris: klinische und genetische Aspekte

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