mutation gene disorders epidermodysplasia verruciformis
TRANSCRIPT
Epidermodysplasia verruciformis
Tree man illnes
is an extremely rare autosomal recessive genetic hereditary skin
disorder associated with a high risk of carcinoma of the skin
It is characterized by abnormal susceptibility to humanpapillomaviruses (HPVs) of the skin. The resulting uncontrolled HPVinfections result in the growth of scaly macules and papules,particularly on the hands and feet. It is typically associated with HPVtypes 5 and 8
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The cause of the condition is an inactivating PH mutation in
either the EVER1 or EVER2 genes.
1. which are located adjacent to one
another on chromosome 17
2. he precise function of these genes is
not yet fully understood, but they
play a role in regulating the
distribution of zinc in the cell
nuclei
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•Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated
with a high risk of skin cancer (Ramoz et al., 2000). EV results from an
abnormal susceptibility to specific related human papillomavirus (HPV)
genotypes and to the oncogenic potential of some of them, mainly HPV5.
Infection with EV-associated HPV leads to the early development of
disseminated flat wart-like and pityriasis versicolor-like lesions.
•Patients are unable to reject their lesions, and cutaneous Bowen carcinomas
in situ and invasive squamous cell carcinomas develop in about half of
them, mainly on sun-exposed areas.
1. Deletion/duplication analysis
2. Sequence analysis of the entire coding region
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•This oligonucleotide microarray-based assay allows for the detection of
exonic deletions or duplications of 105 genes currently tested in our
laboratory
•This is a custom designed array ( ~140,000 probes present in a 4x180K
format with probes more densely spaced in the exons of the genes being
tested.)
•The array has been designed to detect copy number changes as small
as 300-400 bp.
•Single genes and custom panels of clinically related genes can be
analyzed for deletions and duplications and results may be confirmed
by qPCR, MLPA or alternative methodologies.
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• This assay will allow deletion/duplication analysis for disorders
known to be caused by deletions or duplications within a single gene as
well as for disorders for which the frequency of gene
deletions/duplications is currently not well established.
• The array-CGH test is particularly indicated for disorders resulting
from loss of function or haploinsufficiency.
• In addition, testing for exonic deletions/duplications is useful in
autosomal recessive conditions in which only one mutation is
identified by sequence analysis.
• This assay will detect exonic deletions/duplications of the 105 genes on
the array that may not be detected by whole genome array CGH.
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• Diagnosis of EV should be suspected in the clinical setting ofnumerous verrucous lesions or when lesions are resistant to appropriatetherapy. It is based on clinical and histological findings. Skin biopsyshows verruca plana-like lesions with mild hyperkeratosis,hypergranulosis and acanthosis of the epidermis. Keratinocytes of theupper epidermal layers are enlarged with perinuclear vacuolization and atypical blue-gray pallor.
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Human papillomaviruses
• A nested PCR that enables the detection of all known EV HPV types at
relatively low-copy-number levels.
•The deduced sequences of a 92-amino-acid stretch of the L1 open reading
frames of all types are shown for convenient typing.
•The technique proved very valuable in viral studies of skin cancers from
renal transplant recipients. A high prevalence (81%) of EV HPV types was
found in skin cancer biopsies. A wide spectrum of EV HPV types that differed
from HPV-5 and -8 was found to be involved.
•The technique also proved useful in detecting potentially novel EV HPV
types in skin cancers. The relationship of these new types to known HPV
types is demonstrated by phylogenetic tree analysis.
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• The sum of the sequences coding for potential protein genes occupies 87%
of the genome length.
•By adding rRNA and tRNA genes, therefore, the genome has a very compact
arrangement of protein- and RNA-coding regions.
•A notable feature on the gene organization of the genome was that 99 ORFs,
which showed similarity to transposase genes and could be classified into 6
groups, were found spread all over the genome, and at least 26 of them
appeared to remain intact.
•The result implies that rearrangement of the genome occurred frequently
during and after establishment of this species.
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No serious treatmentAkash Mali
•Several treatments have been suggested, and acitretin 0.5–1 mg/day for 6
months’ duration is the most effective treatment owing to antiproliferative
and differentiation-inducing effects.
•Interferons can also be used effectively together with retinoids.
•Cimetidine was reported to be effective because of its depressing mitogen-
induced lymphocyte proliferation and Regulatory T cell activity features
•Hayashi et al. applied topical calcipotriol to a patient with a successful
result.
•most important, education of the patient, early diagnosisand excision of the tumoral lesions take preference toprevent the development of cutaneous tumors.
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VICTIMS
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•Pereira de Oliveira WR, Carrasco S, Neto CF, Rady P, Tyring SK (March2003)."Nonspecific cell-mediated immunity in patients with epidermodysplasiaverruciformis HPV". The Journal of Dermatology 30 (3): 203–9. PMID 12692356.
•Allen, Mark (12 March 2007). "Missionary encounters extremely bizarre skincondition in Eastern Europe". Beware of the Blog. WFMU. Retrieved 6August 2009.
•"The man who looks like a tree". Metro. 22 November 2007. Retrieved 6August 2009.
•“ Half Man Half Tree". Discovery Channel. Retrieved 6 August 2009.
•""Tree Man" Medical Mystery". ABC News. 15 August 2008. Retrieved 19December2012.
•Dipa, A. (13 January 2011). "‘Tree man’ undergoes 2-hour surgery to removewarts".The Jakarta Post. Retrieved 18 May 2011. Akash Mali
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