SM 259: Genetic Disease Flashcards
What are Ichthyoses?
Greek for scaly fish; a group of disorders grouped due to characteristic skin thickening and scaling
Why does skin thickening and scaling occur in Ichthyoses?
Believed to be a compensatory mechanism to poor epidermal barrier formation
What is the most common form of Ichythoses?
Ichythyoses Vulgaris
How does Ichythyoses Vulgaris present?
Scaling on the lower legs, and mild thickening/hyperlinearity of the palms and soles
What causes Ichythyoses Vulgaris?
A mutation in the gene encodes Filaggrin, leading to a decrease in the Stratum Granulosum of the Epidermis which normally contains Filaggrin granules
Why is Ichythyoses Vulgaris “semidominant”?
Loss of 1 Fillagrin allele leads to a milder phenotype than if both alleles are effect (which is lethal)
What is Recessive X-linked Ichthyosis?
A recessive X-linked Ichthyosis that only occurs in males, which effects the enzyme Steroid Sulfatase
What enzyme is effected by Recessive X-linked Ichthyosis, and what does this cause?
Steroid Sulfatase; leading to an accumulation of Cholesterol Sulfate in the Epidermis and blood
What is “collodion baby”?
A rare group of Ichthyosis which results in a baby with a shiny cellophan elike membrane due to a Autosomal Recessive conditions
Includes Lamellar Ichthyosis (TGM) and CIE
Eventually resolves and becomes a different Ichthyosis
What gene is mutated in the AR Congenital Ichthyosis Lamellar Ichthyosis that causes Collodion baby?
Transglutainase 1, an enzyme needed for normal maturation of and shedding of epidermal cells, is lost, leading to large platelike scales and Collodion baby
What is Congenital Ichthyosiform Erythroderma?
An AR Congenital Ichthyosis due to 10 potential mutations that causes fine scaling
What group of Ichthyosis has blisters?
Epidermolytic Icthyosis - an Autosomal Dominant condition
How does Epidermolytic Ichthyosis present?
A superficial blistering disorder at birth that later changes to thickening to compensate for the barrier abnormality
What genes are mutated in Epidermolytic Ichthyosis?
Keratins 1 and 10, found above the basal areas of the epidermis, may be mutated, leading to blistering
Which Keratins are mutated in blistering disorders, and where are they found?
Keratins 1 and 10, found in above basal layer of the epidermis, and mutations cause disorders like Epidermolytic Ichthyosis
Keratins 5 and 14, found in the basal layer of the epidermis, cause Epidermolytic Bullosa Simplex
Which Keratin is found in palms and soles?
Keratin 9
How could mutations in Keratin 1 and 10 manifest differently in the palm?
Keratin 1 + 9 form pairs in the palm; a mutation in Keratin 10 has only slightly thickened palms, while a mutation in Keratin 1 has severely thickened palms
What Keratins are found in the proliferative basal layer of the Epidermis?
Keratins 5 and 14 are found in the proliferative basal layer
Keratins 1 and 10 are found above the proliferative basal layer
What is Epidermolysis Bulbosa simplex?
A Keratinopathy due to mutations in Keratins 5 or 14, which presents with blistering without significant thickening
What are Junctional Epidermolysis Bulbosa?
An AR group of disorders which result from the absence of Hemidesmosomes, leading to a loss of skin adhesion
Lethal
What is Dystrophic EB?
A group of EB that results from mutations in Type VII Collagen, leading to mild scarring and blistering if 1 allele is lost and severe glistering as well as growth retardation and SCC if both alleles are lost
What are the three tumor syndromes and what causes them?
Mutations that activate signaling pathways cause tumor syndromes, including: Neurofibromatosis, Basal Cell Nevus Syndrome, and Tuberous Sclerosis
What is Neurofibromatosis?
An AD disorder that causes cafe au lait macules and lisch nodules, later leading to dermal neurofibromas and optic gliomas
What causes Neurofibromatosis?
Mutations in Neurofibromin, a tumor suppressor gene that negatively regulates Ras, leading to loss of tumor suppression - a loss of heterozygosity
