PROGERIA (Hutchinson-Guilford syndrome)

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PROGERIA (Hutchinson-Guilford syndrome) Onset of
symptoms generally 6 -24 months. The condition
is distinguished by ? growth failure ? alopecia
? small face and jaw and pinched nose ? dry,
thin, wrinkled skin ? atherosclerosis and
cardiovascular problems ? limited range of
motion, arthritis ? Mental development is not
affected. ? Individuals with the condition rarely
live more than 16 years. The development of
symptoms is comparable to aging at a rate six to
eight times faster than normal, although certain
age-related conditions do not occur.
Specifically, victims show no neurodegeneration
or cancer predisposition.
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Progeria, the classic "accelerated aging disease"
is not caused by defective DNA repair. It is
caused by mutations in a LMNA (Lamin A protein)
gene. Lamin A is part of a protein scaffold
around the edge of the nucleus that helps
organize nuclear processes such as DNA and RNA
synthesis. Prelamin A is farnesylated, enabling
it to bind to the nuclear membrane. The cleavage
site to release Lamin A is mutated. Lamin A
cannot be produced and Prelamin A builds up on
the nuclear membrane
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WERNERS SYNDROME
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Bloom's Syndrome -typical physical
characteristics      Short stature       A
narrow face with prominent nose       Skin
color changes in the face. Change more
noticeable after sunlight exposure     
 Butterfly-shaped facial rash, similar to rash
caused by Lupus Erythematosis       A high
pitched voice       An increased susceptibility
to infections and respiratory illness       An
increased susceptibility to cancer and
leukemia       Some may also have mental
retardation
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Cockayne Syndrome
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Classical Cockayne syndrome (Type I)
progressive symptoms become apparent after 1
year. unlike other DNA repair diseases,
Cockayne syndrome is not linked to cancer
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Fanconi anemia
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Fanconi anemia
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Xeroderma Pigmentosum
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Xeroderma Pigmentosum
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Xeroderma Pigmentosum (XP) condition resulting
from a deletion in the gene for the XPAC protein
of the excision repair system, so that
individuals are unable to reverse TT
dimerization induced by sunlight. XP is
characterized by extremely dry skin and numerous
malignant pinpoint tumors induced after brief
exposure to sunlight. The boy on the left shows
two skin cancers on his nose, and an irregular
distribution of pigment that resembles a severe
sunburn (erythemea). The girl on the right has
avoided sunlight since diagnosis with XP.
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UV-protection suit to help people suffering from
the genetic disorder xeroderma pigmentosum (XP).
It consists of a headgear protecting the head
and face, and a suit covering the rest of the
body, both filtering out 100 UV-light from the
Sun
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Proposed model of the pathogenesis of bone marrow
failure in patients with DKC In this model
excessively short telomeres are the underlying
cause of clinical manifestations in patients with
DKC. Mutations in TERC or TERT affect the
activity of telomerase. Mutations in DKC1
destabilize TERC and/or retard ribosome
biogenesis. As telomeres get shorter there is an
increase in genomic instability leading
eventually to a cell crisis, cell cycle arrest,
and cell death. Rare cells that can maintain
telomere integrity emerge from the crisis as
potentially malignant cells. From Mason PJ,
Wilson DB, Bessler M Dyskeratosis congenita -- a
disease of dysfunctional telomere maintenance.
Curr Mol Med 2005 Mar5(2)159-70
DYSKERATOSIS CONGENITA
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Leukoplakia -- white plaques or patches on the
mucous membranes of the oral cavity, including
the tongue
Dyskeratosis congenita Clinical features ?
abnormal skin pigmentation ? leukoplakia ? nail
dystrophy ? bone marrow failure
Reticulated pigmentation seen in 90 of patients

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Hyperkeratosis occurs on the palms and soles.
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Dyskeratosis congenita Disintegrating nails
appear between ages 5-13 years and are eventually
destroyed.
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? 75 mortality by age 30. ? Bone marrow failure
is a major cause of death, with approximately 75
of deaths related to bleeding and opportunistic
infections as a result of peripheral cytopenia.