Melanoma and non-melanoma (basal and squamous cell carcinoma) skin cancer (NMSC) are now the most common types of cancer in the white populations and the incidence of skin cancer has reached epidemic proportions According to recent population-based studies from Australia the incidence rate is over 2% for basal cell carcinoma in males and 1% for squamous cell carcinoma, and there are over 50 new cases of melanoma per 100 000

The epidemiology of skin cancer.

Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of keratinization and one of the most frequent single-gene disorders in humans. The most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy English schoolchildren. We have identified homozygous or compound heterozygous mutations R501X and 2282del4 in the gene encoding filaggrin (FLG) as the cause of moderate or severe ichthyosis vulgaris in 15 kindreds. In addition, these mutations are semidominant; heterozygotes show a very mild phenotype with incomplete penetrance. The mutations show a combined allele frequency of approximately 4% in populations of European ancestry, explaining the high incidence of ichthyosis vulgaris. Profilaggrin is the major protein of keratohyalin granules in the epidermis. During terminal differentiation, it is cleaved into multiple filaggrin peptides that aggregate keratin filaments. The resultant matrix is cross-linked to form a major component of the cornified cell envelope. We find that loss or reduction of this major structural protein leads to varying degrees of impaired keratinization.

Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris

We recently reported two common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. We show here that these common European mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent. All the variants are either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis. In an Irish case-control study, the five most common European mutations showed a strong association with moderate-to-severe childhood eczema (chi2 test: P = 2.12 x 10(-51); Fisher's exact test: heterozygote odds ratio (OR) = 7.44 (95% confidence interval (c.i.) = 4.9-11.3), and homozygote OR = 151 (95% c.i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles.

Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema.

https://www.jidonline.org/article/S0022-202X(15)35676-1/pdf

One remarkable molecule: Filaggrin

Lamellar ichthyosis type 2 (LI2) is a rare autosomal recessive skin disorder for which a gene has been localized on chromosome 2q33–35. We report the identification of five missense mutations in the ABCA12 gene in nine families from Africa affected by LI2. The mutations were homozygous in eight consanguineous families and heterozygous in one non-consanguineous family. Four of these mutations are localized in the first ATP-binding domain (nucleotide-binding fold), which is highly conserved in all ABC proteins. The ABCA12 protein belongs to a superfamily of membrane proteins that translocate a variety of substrates across extra- and intracellular membranes. ABCA transporters have been implicated in several autosomal recessive disorders, notably of lipid metabolism. By analogy with ABCA3, a lamellar body membrane protein in lung alveolar type II cells, ABCA12 could function in cellular lipid trafficking in keratinocytes.

/pdf/mutations-in-the-transporter-abca12-are-associated-with-3qpzx1hj8d.pdf

Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2

This term is used to describe disorders in which there is a primary fault in the process of epidermal differentiation and (or) desquamation. It includes the ichthyotic disorders and a number of other quite uncommon disorders in which there is scaling and hyperkeratosis.

Disorders of Keratinization

Alterations in the melanin pigmentation of the skin produce abnormal duskiness or whiteness and may be due to many factors. Lightening of the skin may be due to a deficiency of melanin, or a reduction in the number of melanocytes. In albinism there are normal numbers of melanocytes, whereas in vitiligo the number of melanocytes is reduced or absent. This change is difficult to judge in ordinarily stained histological sections but can be assessed by quantitative electron-microscopic studies1, or by performing a DOPA oxidase histochemical test. In a similar fashion, darkening of the skin may be caused by an increase in epidermal or subepidermal melanin or an increase in the number of melanocytes. Thus in Addison’s disease there is an increase of activity of the cutaneous melanocytes without an alteration in their number, whereas in naevi and melanoma the abnormal pigmentation is associated with melanocytic hyperplasia.

Melanocytic Naevi and Malignant Melanoma

Inevitably, reading is one of the requirements to be undergone. To improve the performance and quality, someone needs to have something new every day. It will suggest you to have more inspirations, then. However, the needs of inspirations will make you searching for some sources. Even from the other people experience, internet, and many books. Books and internet are the recommended media to help you improving your quality and performance.

Atlas of Skin Pathology

The skin can develop vesicles and bullae as a result of diverse causes through mechanisms affecting different levels of the epidermis and dermis1. Histological diagnosis of bullous skin disorders requires attention to several key points. These include:

Bullous and Vesicular Skin Disorders

This condition may be the end result of discoid lupus erythematosus, lichen planus, a deep fungus or bacterial infection and pseudopelade of Brocq, although there is some doubt as to whether the last is a separate entity. There is localized scarring atrophy of the scalp with permanent loss of hair follicles.

P. Laidler

Papers

Disorders of Keratinization

Melanocytic Naevi and Malignant Melanoma

Atlas of Skin Pathology

Bullous and Vesicular Skin Disorders

Scalp and Hair Disorders