Hearing impairment caused by mutations in two different genes responsible for nonsyndromic and syndromic hearing loss within a single family.

Usher syndrome is rare genetic disorder impairing two human senses, hearing and vision, with the characteristic late onset of vision loss. This syndrome is divided into three types. In all cases, the vision loss is postlingual, while loss of hearing is usually prelingual. The vestibular functions may also be disturbed in Usher type 1 and sometimes in type 3. Vestibular areflexia is helpful in making a proper diagnosis of the syndrome, but, often, the syndrome is misdiagnosed as a nonsyndromic hearing loss. Here, we present a Polish family with hearing loss, which was clinically classified as nonsyndromic. After excluding mutations in the DFNB1 locus, we implemented the next-generation sequencing method and revealed that hearing loss was syndromic and mutations in the USH2A gene indicate Usher syndrome. This research highlights the importance of molecular analysis in establishing a clinical diagnosis of congenital hearing loss.

[Epidermal barrier - molecular structure and disorders in selected ichthyoses]. / Struktura molekularna bariery naskórkowej i jej zaburzenia w wybranych chorobach z grupy rybiej luski.

Ichthyosis is a rare, clinically heterogeneous group of 36 skin diseases with Mendelian inheritance, characterized by disorders of cornification (MeDOC, Mendelian Disorders Of Cornification). Currently there are 35 genes known which mutations are a molecular cause of different MeDOC. They encode proteins involved in the processes of keratinocytes differentiation, lipid synthesis and metabolism and DNA repair. Despite of this high molecular heterogeneity that leads to dysfunction and structure disorder of various epidermal components, the secondary effect of mutations in different genes is similar - disruption of the epidermal barrier and elevated transepidermal water loss. Disturbances in this basic epidermal protective function activate the repair mechanisms within the epidermis and lead i.a. to the primary symptom of MeDOC - hyperkeratosis. In this review we presented the current knowledge of biochemical processes and molecular causes of clinical symptoms based on selected examples of MeDOC.