medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2018.07.46-51medgen-532Research ArticleКЛИНИЧЕСКИЕ СЛУЧАИCLINICAL CASEМУТАЦИЯ ГЕНА AQP5 - ПРИЧИНА ЛАДОННО-ПОДОШВЕННОГО ГИПЕРКЕРАТОЗА В РОССИЙСКОЙ СЕМЬЕAQP5 MUTATION AS A CAUSE OF PALMOPLANTAR KERATODERMA IN A RUSSIAN FAMILYЩагинаО. А.ShchaginaO. A.ФедотовВ. П.FedotovV. P.

Voronezh.

ФедотоваТ. В.FedotovaT. V.

Voronezh.

ПоляковА. В.PolyakovA. V.Федеральное государственное бюджетное научное учреждение Медико-генетический научный центрРоссияResearch Centre for Medical GeneticsRussian FederationБюджетное учреждение здравоохранения Воронежской области Воронежская областная клиническая больница №1РоссияVOKB #1Russian Federation2018081020181774651Copyright © Щагина О.А., Федотов В.П., Федотова Т.В., Поляков А.В., 20182018Щагина О.А., Федотов В.П., Федотова Т.В., Поляков А.В.Shchagina O.A., Fedotov V.P., Fedotova T.V., Polyakov A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/532

Ладонно-подошвенный гиперкератоз - заболевание, характеризующееся патологическим ороговением кожи ладоней и подошв, приводящему к образованию трещин с последующим их инфицированием. Причиной ладонно-подошвенного гиперкератоза могут являться мутации различных генов или факторы внешней среды. Установление этиологии болезни имеет ключевое значение при выборе тактики лечения и агрессивности терапии. Нами была обследована большая семья с аутосомно-доминантным типом наследования болезни. При анализе сцепления было установлено, что ладонно-подошвенный гиперкератоз сцеплен с локусом 12q13. В результате исследования генов данного локуса была обнаружена причина болезни - патогенный вариант c.369c>G p.(Asn123Lys) гена AQP5.

Hereditary palmoplantar keratoderma (PPK) is characterized by hyperkeratosis  of the skin of palms and soles. PPK type Bothnia was described as having a high prevalence  in the 2 northernmost provinces of Sweden,  situated  to the west and the northwest of the Gulf of Bothnia. In Swedish families with dominant PPK researchers established that the phenotype  had been linked to the most frequent locus 12q13, but no mutations were found in KRT1. Various missense AQP5-mutations were found in all cases. A three-generation family of Chinese Han ethnicity with AQP5-PPK was described later. In a five-generations Russian PPK family the cause of the disease was searched using the linkage analysis, Senger  sequencing, MPS (IlluminaTruSeq® ExomeKit). We found a linkage to locus 12q13. The maximum Lod score of 3.69 was observed on D12S368 (52 631 kb). The area was limited within D12S1661 (48 607kb): Lod - 2.61    = 0 and D12S1586 (54 146 kb): Lod - 3.66     = 0. However, no mutation in KRT1 and over KRT’s genes of this region was revealed. We performed an exome analysis in one of the patients and identified three heterozygous variants in the target region. Two variants in CELA1 and OR8S1 genes did not segregate with the disease in the family and only one AQP5 c.369C>G(p.Asn123Lys) substitution could be a root of the PPC in this family (Lod max — 3.71   = 0.00). We confirmed that the cause of PPK could be mutations in the water-channel aquaporin-5 gene. Our findings have shown that AQP5-PPK can be found in different ethnic groups,  not only in Bothnia region.

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The authors declare that there are no conflicts of interest present.