SCHIZOPHRENIA SUSCEPTIBILITY

Introduction
Schizophrenia is a chronic, severe, and disabling brain disorder that has affected people
throughout history.
People with the disorder may hear voices other people don't hear. They may believe other
people are reading their minds, controlling their thoughts, or plotting to harm them. This can
terrify people with the illness and make them withdrawn or extremely agitated.
People with schizophrenia may not make sense when they talk. They may sit for hours
without moving or talking. Sometimes people with schizophrenia seem perfectly fine until they
talk about what they are really thinking.
Families and society are affected by schizophrenia too. Many people with schizophrenia
have difficulty holding a job or caring for themselves, so they rely on others for help.
Treatment helps relieve many symptoms of schizophrenia, but most people who have the
disorder cope with symptoms throughout their lives. However, many people with schizophrenia
can lead rewarding and meaningful lives in their communities. Researchers are developing more
effective medications and using new research tools to understand the causes of schizophrenia. In
the years to come, this work may help prevent and better treat the illness.

Genetic Factors
It is believed that no one single gene causes the disease by itself but rather that several
genes are associated with an increased risk of schizophrenia. While schizophrenia occurs in one
percent of the general population, having a history of family psychosis greatly increases the risk.
Schizophrenia occurs at roughly ten percent of people who have a first-degree relative with the
disorder, i.e., a parent or sibling. However, the highest risk occurs when an identical twin is
diagnosed with schizophrenia. The unaffected twin has a roughly 50 percent chance of
developing the disorder.
The genetic component appears to extend beyond family environment. For example,
children with a parent living with schizophrenia who were put up for early adoption still develop
schizophrenia at a higher rate than the rest of the of the population.
Specific genes have been shown to influence the risk for developing schizophrenia.
Despite many studies revealing a connection between particular genes and schizophrenia, other
studies have found that those genes do not necessarily increase the risk of schizophrenia.

Epidemiology
Schizophrenia occurs throughout the world. The prevalence of schizophrenia (ie, the
number of cases in a population at any one time point) approaches 1 percent internationally. The
incidence (the number of new cases annually) is about 1.5 per 10,000 people . Slightly more men
are diagnosed with schizophrenia than women (on the order of 1.4:1) , and women tend to be
diagnosed later in life than men. There is also some indication that the prognosis is worse in
men.
A number of risk factors have been associated with the development of schizophrenia,
including living in an urban area , immigration, obstetrical complications, and a late winter-early
spring time of birth (perhaps reflecting exposure to influenza virus during neural development).
Advanced paternal age at conception has been associated with increased risk of schizophrenia in
epidemiologic studies, and may be associated with an increased risk of de novo mutations.

Diagnostic Procedures
There is no test that can make a schizophrenia diagnosis. People with
schizophrenia usually come to the attention of a mental health professional after others see them
acting strangely. Doctors make a diagnosis through interviews with the patient as well as with
friends and family members. Schizophrenia symptoms have been present for at least six months.
Patient is significantly impaired by the symptoms. For example, has serious difficulty working or
with social relationships, compared to the period before symptoms began. Symptoms can't be
explained by another diagnosis, such as drug use or another mental illness.
Some people with schizophrenia are afraid of their symptoms. Or they may be suspicious
of others (paranoid). They may conceal their symptoms from doctors or loved ones. This can
make it more difficult to confirm a schizophrenia diagnosis.
People with schizophrenia have at least some of its main symptoms. For a psychiatrist to
make a confident schizophrenia diagnosis, some of these symptoms must be present:
Hallucinations. This means hearing voices or other sounds that aren't there or seeing things that
don't exist. Delusions (unshakeable beliefs that aren't true). Disorganized speech and behavior
(talking and acting strangely). Lack of motivation and emotional expression. Lack of energy.
Poor grooming habits.
Specific types of psychotic symptoms (called first-rank symptoms), when present, make a
schizophrenia diagnosis more likely: hearing your own thoughts spoken aloud, feeling that
thoughts are being inserted into your mind, or removed from it, by an outside force, feeling like
other people can read your mind, feeling that an outside force is making you feel something,
want something, or act in a certain way, hearing voices discuss you or argue about you, and
hearing voices narrate your actions as you perform them.
A person with schizophrenia may describe these symptoms openly. Or a psychiatrist may
deduce they are likely present based on observations of a person's speech and behavior.


References:

NIMH Schizophrenia. (n.d.). Retrieved September 26, 2013, from
http://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml

Schizophrenia: Epidemiology and pathogenesis. (n.d.). Retrieved September 26, 2013, from
http://www.uptodate.com/contents/schizophrenia-epidemiology-and-pathogenesis

Schizophrenia Diagnosis. (n.d.). Retrieved September 26, 2013, from
http://www.webmd.com/schizophrenia/guide/schizophrenia-tests





XERODERMA PIGMENTOSUM
Introduction
Xeroderma pigmentosum (XP) was first described in 1874 by Hebra and Kaposi. In 1882,
Kaposi coined the term xeroderma pigmentosum for the condition, referring to its characteristic
dry, pigmented skin. Xeroderma pigmentosum is a rare disorder transmitted in an autosomal
recessive manner. It is characterized by photosensitivity, pigmentary changes, premature skin
aging, and malignant tumor development.

These manifestations are due to a cellular
hypersensitivity to ultraviolet (UV) radiation resulting from a defect in DNA repair.

Genetic Factors
Xeroderma pigmentosum is caused by mutations in genes that are involved in repairing
damaged DNA. DNA can be damaged by UV rays from the sun and by toxic chemicals such as
those found in cigarette smoke. Normal cells are usually able to fix DNA damage before it
causes problems. However, in people with xeroderma pigmentosum, DNA damage is not
repaired normally. As more abnormalities form in DNA, cells malfunction and eventually
become cancerous or die.
Many of the genes related to xeroderma pigmentosum are part of a DNA-repair process
known as nucleotide excision repair (NER). The proteins produced from these genes play a
variety of roles in this process. They recognize DNA damage, unwind regions of DNA where the
damage has occurred, snip out (excise) the abnormal sections, and replace the damaged areas
with the correct DNA. Inherited abnormalities in the NER-related genes prevent cells from
carrying out one or more of these steps. The POLH gene also plays a role in protecting cells from
UV-induced DNA damage, although it is not involved in NER; mutations in this gene cause the
variant type of xeroderma pigmentosum.

Epidemiology
This condition is inherited in an autosomal recessive pattern, which means both copies of
the gene in each cell have mutations. The parents of an individual with an autosomal recessive
condition each carry one copy of the mutated gene, but they typically do not show signs and
symptoms of the condition.
Xeroderma pigmentosum is a rare disorder; it is estimated to affect about 1 in 1 million
people in the United States and Europe. The condition is more common in Japan, North Africa,
and the Middle East.

Diagnostic Procedures
The diagnosis of XP is made on the basis of clinical findings and family history. The
preferred method of laboratory diagnosis is functional testing to screen cells for abnormalities
in DNA repair. XP has been classified by complementation group (XP-A, XP-B, XP-C, XP-D,
XP-E, XP-F, XP-G) based on research laboratory testing. The XP complementation groups are
associated with biallelic mutations in XPA, ERCC1, ERCC3 (XP-B), XPC, ERCC2 (XP-
D), DDB2 (XP-E), ERCC4 (XP-F), and ERCC5 (XP-G). In addition XP is associated with
mutations in POLH.


References:
GeneReviews. (2005). Seattle, WA: University of Washington. Available :
http://www.ncbi.nlm.nih.gov/books/NBK51784/

Xeroderma pigmentosum. Retrieved September 26, 2013, from
http://emedicine.medscape.com/article/1119902-overview






































GROUP G COAGULATION FACTOR VII DEFICIENCY
Introduction
(Can also be known as Alexanders disease, stable factor deficiency, or proconvertin
deficiency. Not to be confused with acquired factor VII deficiency, which is associated with
liver disease.)
Factor VII was first recognized in 1951, and originally named serum prothrombin version
accerlerator (SPCA) deficiency. Although the published incidence of Factor VII deficiency is
estimated at 1 in 500,000, the disorder may be more common. It is inherited in an autosomal
recessive fashion, which means it affects men and women equally.
The factor VII protein is part of the cascade of clotting factors that form the chain leading
to a protective blood clot. Factor VII deficiency is usually severe. In fact patients with less than
1% Factor VII activity experience similar symptoms to hemophilia. People with severe factor
VII are prone to joint bleeds. In addition to spontaneous nosebleeds, people can experience
bleeds in the stomach, intestines and urinary tract. Head bleeds and muscle bleeds have also
been reported. Women can have severe menorrhagia.

Genetic Factors
The FVII gene is situated on the long arm of chromosome 13 and consists of nine exons
preceded by a promoter region, globally spanning approximately 12 kb near the telomere. Genes
for two other vitamin K-dependent proteins, FX and PROZ, are placed closely to the FVII gene.
Variations in the sequence are comprehensive of gene polymorphisms and a wide spectrum of
mutations. Gene polymorphic sites associated with variations in FVII levels have been
extensively studied, and their contribution to arterial thrombotic events, such as stroke,
myocardial infarction and peripheral arterial disease, is still debated

Epidemiology
Hereditary factor VII deficiency is a rare autosomal recessive bleeding disorder first
described by Alexander et al in 1951. Prevalence is estimated to be 1 case per 500,000 persons in
the general population. Dubin-Johnson syndrome and Rotor syndrome are associated with a high
prevalence of factor VII deficiency. Acquired factor VII deficiency from inhibitors is very rare.
Cases have been reported with the deficiency occurring in association with drugs such as
cephalosporins, penicillins, and oral anticoagulants. Acquired factor VII deficiency has also been
reported to occur spontaneously or with other conditions, such asmyeloma, sepsis, and aplastic
anemia, and with interleukin-2 therapy and antithymocyte globulin therapy.
Morbidity and mortality rates vary with the severity of the factor deficiency. Severe
factor VII deficiencies (< 1%) result in bleeding disorders indistinguishable from
severe hemophilia A or hemophilia B. Specific mutations and polymorphisms are known to
occur in some populations. Among Iranian and Moroccan Jews, a missense Ala244Val mutation
is responsible for frequent occurrences of disease. The highest frequencies of the polymorphism,
an Arg353Gln substitution, are observed in Gujaratis (25%) and Dravidian Indians (29%)
compared with northern Europeans (9%) and Japanese (3%), resulting in decreases in factor VII
levels. Factor VII deficiency has no reported predilection for either sex. Factor VII deficiency
has no reported predilection for any particular age group.


Diagnostic Procedures
Factor VII deciency can be easily suspected when a haemostatic screening reveals an
isolated prolongation of the PT with a normal activated partial thromboplastin time. The FVIIc
assay is easily available, but pitfalls exist because of the inuence of the different
thromboplastins on the specic assay; also, the residual levels of tiny amounts of FVII in the
substrate used for the assay play a role in reducing the sensitivity of the assay. Recently, the use
of a standardized reference plasma as a calibrator and the supply of a recombinant
thromboplastin as a common reagent have been shown to reduce the variability of inter-
laboratory determinations particularly of low to very low plasma FVIIc level.
Molecular diagnosis is based on the conventional PCR techniques, and considering the
poor relationship between FVIIc and the bleeding tendency, it is helpful in unsolved cases or in
cases in which inheritance pattern in not clear. As mentioned, more complex intragenic
rearrangements escaping the conventional PCR-based techniques can be detected by semi-
quantitative multiplex PCR, thus providing a full mutational status in FVII deciency. Prenatal
diagnosis is available and should be proposed only when a family history with severe bleeding is
present. Cord blood is usually obtained by either the trans-abdominal or trans-amniotic approach,
and genetic analysis performed on blood samples is the gold standard method. In case mutational
gene analysis is unavailable, considering the rarity of the defect, FVIIc assay obtained by
cordocentesis between the 17th and 21st weeks of gestation is feasible, but reconrmation is
needed after birth. As an alternative, prenatal diagnosis can be performed on amniocentesis
during the early stage of pregnancy.



References:

Factor VII deficiency. (n.d.). Retrieved September 26, 2013, from
http://emedicine.medscape.com/article/209585-overview#a0199


Factor VII Deficiency. (n.d.). Retrieved September 26, 2013, from
http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=187&contentid=50


Factor VII deficiency. (2001) Canadian Hemophilia Society. Retrieved 26 September 2013,
from http://www.hemophilia.ca/en/bleeding-disorders/other-factor-deficiencies/factor-vii-
deficiency/


















Other

Dominantly and recessively inherited cornea plana congenita map. (n.d.).
Retrieved September 26, 2013, from http://genome.cshlp.org/content/6/4/249.full.pdf



Cornea Plana | Hereditary Ocular Diseases. (n.d.). Retrieved September 26, 2013, from
http://disorders.eyes.arizona.edu/disorders/cornea-plana




Orphanet Journal of Rare Diseases | Full text | Brachydactyly. (n.d.). Retrieved from
http://www.ojrd.com/content/3/1/15