Mutation

Disorders

Angelo Jay F. Pedro

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A genetic disorder is a disease caused in whole or in part by a change
in the DNA sequence away from the normal sequence. Genetic
disorders can be caused by a mutation in one gene (monogenic
disorder), by mutations in multiple genes (multifactorial inheritance
disorder), by a combination of gene mutations and environmental
factors, or by damage to chromosomes (changes in the number or
structure of entire chromosomes, the structures that carry genes).

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 1 BACKROUND
As we unlock the secrets of the human
genome (the complete set of human
genes), we are learning that nearly all
diseases have a genetic component.
Some diseases are caused by
mutations that are inherited from the
parents and are present in an Factors that Causes Genetic Disorder
individual at birth, like sickle cell
disease. Other diseases are caused by
acquired mutations in a gene or group
of genes that occur during a person's 1 Environmental Factors
life. Such mutations are not inherited
from a parent, but occur either
2 Single Gene Inheritance

randomly or due to some 3 Multifactoral Inheritance

environmental exposure (such as
cigarette smoke). These include many 4 Cheromosome Abnormalities
cancers, as well as some forms of
neurofibromatosis. 5 Mitocondiral Inheritance
INTRODUCTION Before knowing the different types of mutation disorder here
is a reference video to understand why it happens:

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5 Mutation Disorders

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 P – Point mutation, or any insertion/deletion entirely inside one gene
D – Deletion of a gene or genes
C – Whole chromosome extra, missing, or both (see chromosome abnormality)
T – Trinucleotide repeat disorders: gene is extended in length

Cystic Fibrosis Angelman Canavan Di George’s Waardenberg

Disorder Disorder Disorder Disorder Disorder
PAX3, MITF,
WS2B,WS2C,
15 15b 17p 22q11.2 SNAI2, EDNRB,
EDN3, SOX 10
Chromosome Chromosome Chromosome Chromosome Chromosome

P DCP D dominant
Mutation Mutation Mutation Mutation Mutation
 1 What is Cystic Fibrosis?
Cystic fibrosis is a progressive, genetic disease that
causes persistent lung infections and limits the ability
to breathe over time.
In people with CF, mutations in the cystic fibrosis
transmembrane conductance regulator (CFTR) gene
cause the CFTR protein to become dysfunctional.
When the protein is not working correctly, it’s unable
to help move chloride -- a component of salt -- to the
cell surface. Without the chloride to attract water to
the cell surface, the mucus in various organs becomes
thick and sticky.
In the lungs, the mucus clogs the airways and traps
germs, like bacteria, leading to infections, 
inflammation, respiratory failure, and other
complications. For this reason, 
minimizing contact with germs is a top concern for
people with CF.
 2 Diagnosis and Genetics

Cystic fibrosis is a genetic disease. People with CF have According to the Cystic
inherited two copies of the defective CF gene -- one copy Fibrosis Foundation Patient
from each parent. Both parents must have at least one Registry, in the United
copy of the defective gene. States:
People with only one copy of the defective CF gene are More than 30,000 people are
called carriers, but they do not have the disease. Each time living with cystic fibrosis
two CF carriers have a child, the chances are: (more than 70,000
25 percent (1 in 4) the child will have CF worldwide).
50 percent (1 in 2) the child will be a carrier but will not Approximately 1,000 new
have CF cases of CF are diagnosed
25 percent (1 in 4) the child will not be a carrier and will each year.
not have CF More than 75 percent of
The defective CF gene contains a slight abnormality called people with CF are diagnosed
a mutation. There are more than 1,700 known mutations by age 2.
of the disease. Most genetic tests only screen for the most More than half of the CF
common CF mutations. Therefore, the test results may population is age 18 or
indicate a person who is a carrier of the CF gene is not a older. 
carrier. 8
 3 What to Expect?

Cystic fibrosis is a complex disease and the types and

Nightmare of having C.
severity of symptoms can differ widely from person to
person. Many different factors, such as age of diagnosis,
fibrosis:
can affect an individual's health and the course of the
disease.

Tremendous advancements in specialized CF care have

added years and quality of life to the lives of people with
cystic fibrosis. There have been dramatic improvements
from the 1950s, when a child with CF rarely lived long
enough to attend elementary school to today, with many
living long enough to realize their dreams of attending 
college, pursuing careers, getting married, and having kids
.

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 1 What is Angelman’s
Syndrome?
Angelman syndrome is a genetic disorder. It causes
delayed development, problems with speech and balance,
intellectual disability, and sometimes, seizures.
People with Angelman syndrome often smile and laugh
frequently, and have happy, excitable personalities.
Developmental delays, which begin between about 6 and
12 months of age, are usually the first signs of Angelman
syndrome. Seizures may begin between the ages of 2 and
3 years old.
People with Angelman syndrome tend to live close to a
normal life span, but the disorder can't be cured.
Treatment focuses on managing medical, sleep and
developmental issues.

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 2 What causes Angelman’s
Syndrome?

Angelman syndrome is a genetic disorder. It's usually

caused by problems with a gene located on chromosome
15 called the ubiquitin protein ligase E3A (UBE3A) gene.
A missing or defective gene
You receive your pairs of genes from your parents — one
copy from your mother (maternal copy) and the other
from your father (paternal copy).
Your cells typically use information from both copies, but
in a small number of genes, only one copy is active.
Normally, only the maternal copy of the UBE3A gene is
active in the brain. Most cases of Angelman syndrome
occur when part of the maternal copy is missing or
damaged.
In a few cases, Angelman syndrome is caused when two
paternal copies of the gene are inherited, instead of one
from each parent. 11
 3 Risk and Complications
Risk factors

Angelman syndrome is rare. Researchers usually don't know what causes the genetic changes that result in
Angelman syndrome. Most people with Angelman syndrome don't have a family history of the disease.
Occasionally, Angelman syndrome may be inherited from a parent. A family history of the disease may increase a
baby's risk of developing Angelman syndrome.

Complications
Complications associated with Angelman syndrome include:
•Feeding difficulties. Difficulty coordinating sucking and swallowing may cause feeding problems in infants. Your
pediatrician may recommend a high-calorie formula to help your baby gain weight.
•Hyperactivity. Children with Angelman syndrome often move quickly from one activity to another, have a short
attention span, and keep their hands or a toy in their mouths. Hyperactivity often decreases with age, and
medication usually isn't necessary.
•Sleep disorders. People with Angelman syndrome often have abnormal sleep-wake patterns and may require
less sleep than most people. Sleep difficulties may improve with age. Medication and behavior therapy may help
control sleep disorders.
•Curvature of the spine (scoliosis). Some people with Angelman syndrome develop an abnormal side-to-side
spinal curvature over time.
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•Obesity. Older children with Angelman syndrome tend to have large appetites, which may lead to obesity.
 1 What is Canavan Disease?

Canavan disease is a progressive, fatal, genetic disorder affecting the central nervous

system, muscles, and eyes. Early symptoms in infancy may include increased head size,
weakness, low muscle tone and loss of head control. Symptoms progress to seizures,
blindness, inability to move voluntarily and difficulty eating solids or swallowing liquids.
This condition is caused by changes in the ASPA gene and is inherited in an autosomal
recessive pattern. Canavan disease is diagnosed based on symptoms, laboratory testing,
and genetic testing. There is no specific treatment. Treatment is focused on managing
symptoms.

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2 Causes and Inheritance

Canavan disease is caused by genetic alterations in the ASPA gene.

Canavan disease is inherited in an autosomal
recessive pattern.[4] All individuals inherit two copies of
each gene. Autosomal means the gene is found on one of
the numbered chromosomes found in both sexes.
Recessive means that both copies of the responsible gene
must be altered to have the condition.

People with autosomal recessive conditions inherit one

alteration from each of their parents. The parents, who
each have one gene alteration, are known as carriers. 
Carriers of an autosomal recessive condition typically do
not have any signs or symptoms (they are unaffected).
When two carriers of an autosomal recessive condition
have children, there is a 25% (1 in 4) chance to have a
child with the condition.
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3 Treatment
•There is no specific treatment for Canavan disease.
Treatment is aimed at preventing and/or managing the
known symptoms and complications associated with this
condition. This may include seizure medication, physical
and other therapies, and maintenance of food and water
intake.[1][2][4]

Specialists who might be involved the care of someone

with Canavan disease include:Neurologist
•Ophthalmologist (eye doctor)
•Genetics specialist (genetic counselor and/or geneticist)
•Physical therapist
•Gastroenterologist

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 1 What is Di George’s
Syndrome?
DiGeorge syndrome, more accurately known by a broader term — 22q11.2
deletion syndrome — is a disorder caused when a small part of
chromosome 22 is missing. This deletion results in the poor development
of several body systems.
The term 22q11.2 deletion syndrome covers terms once thought to be
separate conditions, including DiGeorge syndrome, velocardiofacial
syndrome and other disorders that have the same genetic cause, though
features may vary slightly.
Medical problems commonly associated with 22q11.2 deletion syndrome
include heart defects, poor immune system function, a cleft palate,
complications related to low levels of calcium in the blood, and delayed
development with behavioral and emotional problems.
The number and severity of symptoms associated with 22q11.2 deletion
syndrome vary. However, almost everyone with this syndrome needs
treatment from specialists in a variety of fields.

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 2 Causes of Di George’s
Syndrome
Each person has two copies of chromosome 22, one inherited from
each parent. If a person has DiGeorge syndrome (22q11.2 deletion
syndrome), one copy of chromosome 22 is missing a segment that
includes an estimated 30 to 40 genes. Many of these genes haven't
been clearly identified and aren't well-understood. The region of
chromosome 22 that's deleted is known as 22q11.2.
The deletion of genes from chromosome 22 usually occurs as a random
event in the father's sperm or in the mother's egg, or it may occur early
during fetal development. Rarely, the deletion is an inherited condition
passed to a child from a parent who also has deletions in chromosome
22 but may or may not have symptoms.

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 3 Complications
The portions of chromosome 22 deleted in DiGeorge
syndrome (22q11.2 deletion syndrome) play a role in the
development of a number of body systems. As a result,
the disorder can cause several errors during fetal
development. Common problems that occur with 22q11.2
deletion syndrome include:
•Heart defects. 22q11.2 deletion syndrome often causes heart defects
that could result in an insufficient supply of oxygen-rich blood. For
example, defects may include a hole between the lower chambers of the
heart (ventricular septal defect); only one large vessel, rather than two
vessels, leading out of the heart (truncus arteriosus); or a combination of
four abnormal heart structures (tetralogy of Fallot).
•Distinct facial features. A number of particular facial features may be
present in some people with 22q11.2 deletion syndrome. These may
include small, low-set ears, short width of eye openings (palpebral
fissures), hooded eyes, a relatively long face, an enlarged nose tip
(bulbous), or a short or flattened groove in the upper lip.

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 4 Preventions

In some cases, DiGeorge syndrome (22q11.2 deletion

syndrome) may be passed from an affected parent to a
child. If you're concerned about a family history of 22q11.2
deletion syndrome, or if you already have a child with the
syndrome, you may want to consult a doctor who
specializes in genetic disorders (geneticist) or a genetic
counselor for help in planning future pregnancies.

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 1 What is Waandenberg
Syndrome?
Waardenburg syndrome is a group of genetic conditions that can
cause hearing loss and changes in coloring (pigmentation) of
the hair, skin, and eyes. Although most people with
Waardenburg syndrome have normal hearing, moderate to
profound hearing loss can occur in one or both ears. The
hearing loss is present from birth (congenital). People with this
condition often have very pale blue eyes or different colored
eyes, such as one blue eye and one brown eye. Sometimes one
eye has segments of two different colors. Distinctive hair
coloring (such as a patch of white hair or hair that prematurely
turns gray) is another common sign of the condition. The
features of Waardenburg syndrome vary among affected
individuals, even among people in the same family

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 2 Causes of Waadenburg
Syndrome
Mutations in the EDN3, EDNRB, MITF, PAX3, SNAI2, and  Waardenburg syndrome types I and III are caused
SOX10 genes can cause Waardenburg syndrome. These genes by mutations in the PAX3 gene. Mutations in
are involved in the formation and development of several types the MITF or SNAI2 gene can cause Waardenburg
of cells, including pigment-producing cells called melanocytes. syndrome type II.
Melanocytes make a pigment called melanin, which Mutations in the SOX10, EDN3, or EDNRB gene
contributes to skin, hair, and eye color and plays an can cause Waardenburg syndrome type IV. In
essential role in the normal function of the inner ear. addition to melanocyte development, these genes
Mutations in any of these genes disrupt the normal are important for the development of nerve cells
development of melanocytes, leading to abnormal in the large intestine. Mutations in one of these
pigmentation of the skin, hair, and eyes and problems with genes result in hearing loss, changes in
hearing. pigmentation, and intestinal problems related to
Hirschsprung disease.
In some cases, the genetic cause of Waardenburg
syndrome has not been identified.

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 3 Frequency and inheritance
of Waadenburg Syndrome
Waardenburg syndrome is usually inherited in an autosomal Waardenburg syndrome affects an estimated 1 in
dominant pattern, which means one copy of the altered gene in 40,000 people. It accounts for 2 to 5 percent of
each cell is sufficient to cause the disorder. In most cases, an all cases of congenital hearing loss. Types I and II
affected person has one parent with the condition. A small are the most common forms of Waardenburg
percentage of cases result from new mutations in the gene syndrome, while types III and IV are rare.
; these cases occur in people with no history of the
disorder in their family.

Some cases of Waardenburg syndrome type II and type IV

appear to have an autosomal recessive pattern of inheritance,
which means both copies of the gene in each cell have
mutations. Most often, the parents of an individual with an
autosomal recessive condition each carry one copy of the
mutated gene, but do not show signs and symptoms of
the condition.
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THANK YOU!

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