An overview on mutation disease, causes, genetic basis, etiology, epidemiology and management.

1. Diseases of
Genetic Mutation

2. Introduction
A gene is the region of DNA that encodes the primary
sequence of some final gene product which can either be a
polypeptide or RNA with a structural or characteristic
function
Exons; these are regions of DNA occupied by genes
Introns; these are regions of DNA that do not code for
structural or catalytic product but rather act as promoter site,
termination site etc

3. M
U
T
A
T
I
O
N
Mutation is the permanent change
in the sequence or number of
nucleotide in a DNA or structure or
number of chromosomes in a cell
TYPES
Chromosomal; this is the change is
structure or number of
chromosomes in a cell
 Deletion
 Duplication
 Inversion
 Translocation
 Non-disjunction

4. M
U
T
A
T
I
O
N
Gene mutation (mendelian); this occurs due to a change in
the nucleotide sequence or number in a certain gene
within a DNA.
 Point
I. Nonsense
II. Missense
III. Silent
 Frameshift
 Splice site

5. Mutagenic Factors
Physical Agents
 X-ray,
 UV ray,
 Hyperthermia
Chemical Agents
 Thalidomide,
 Nitrous acid,
 5-aminopurine,
 SSRI,
 Opioids,
 Alcohol
Infectious Agents
 Rubella virus,
 Herpes simplex,
 Cytomegalomas

6. DISORDERS CAUSED
BY MUTATION

7. Klinefelter Syndrome
This is a genetic mutation occurring in males due to presence of an
extra X chromosome. It affects about 1 in every 500 males.
Cause;
Non-disjunction of sex chromosomes during cell
division.
Clinical features;
Sterility (testicular atrophy and hyalinization of
seminiferous tubules), abnormal body proportion,
gynecomastia, small size penis
Treatment;
Testosterone therapy

8. Hemophilia
It is an x-linked recessive blood disorder in which blood does not
clot properly. Occurs 1 in every 500 male, Type A is 4 times more
common than Type B.
Cause;
Mutation in F8 and F9 gene cause Haemophilia A and Haemophilia B
respectively
Clinical Features;
Hematoma, Bleeding from mouth and gum, Presence of blood in stool
and in urine
Treatment;
Injection of clotting factors, clotting promoter

9. Fragile X Syndrome
This is a genetic condition which causes intellectual disability
alongside some spectrum of disorders. It occurs 1 in 4000 males
and 1 in 8000 females
Cause;
This form of mutation is caused by CGG trinucleotide
expansion in Xq27 in the FMR1 gene.
Clinical features;
Intellectual disability, ADHD and anxiety, autism spectrum
disorder, large ears and prominent jaws , large testes, seizures
and flat feet.

10. Sickle Cell Anemia
Sickle cell anemia is an inherited blood disorder, characterized by
sickle shaped red blood cells. It is also called hemoglobin SS
disease and it is a type of sickle cell disease. It is common in people
of African origin.
Other types of sickle cell diseases include Sickle Hemoglobin-C
Disease (SC), Sickle Beta-Plus Thalassemia and Sickle Beta-Zero
Thalassemia.

11. Epidemiology
The number of people living with sickle cell disease
globally increased by 41·4% (38·3–44·9), from 5·46
million (4·62–6·45) in 2000 to 7·74 million (6·51–9·2)
in 2021.
About 50 million people are living with SCD globally
and Nigeria is the epicentre zone with about 4-6
million people living with the disease (1 in every 4
Nigerians has a sickle cell trait) Annually, about
300,000 newly diagnosed SCD children are born
worldwide.

12. Sickle cell disease is caused by inheriting
the sickle cell gene.
This usually happens when both parents
are "carriers" of the sickle cell gene, also
known as having the sickle cell trait.
Or it can happen when 1 parent has sickle
cell disease and the other is a carrier of it.
What Causes the Disease?

13. Genetic Basis
Point

14. Manifestation
We have a wide range of
manifest that varies from
person to person and can
change over time.
Some of the manifestations
include:
 Anemia
 Episodes of pain
 Frequent infections
 Jaundice
 Swelling of hands and
feet
 Frontal bossing, etc.
Treatment
1. Bone marrow transplant
2. Transfusion
3. Drugs like
 Hydroxyurea,
 L-glutamine,
 Penicillin, etc.
4. Gene therapy

15. Down Syndrome
Down syndrome, also known as trisomy 21, is a chromosomal
condition characterized by the presence of an extra copy of
chromosome 21. This additional genetic material alters gene
expression and development, leading to a range of physical and
cognitive features

16. Down syndrome remains the most common chromosomal condition
diagnosed in the United States. Each year, about 6,000 babies born in
the United States have Down syndrome. This means that Down
syndrome occurs in about 1 in every 700 babies.
Studies of Down's syndrome covering a period of 9 years revealed an
incidence of 1 in 865 livebirths in a Nigerian hospital. Cytogenetic
analysis in 386 patients showed 369 (95.5%) cases to be the result of
regular trisomy 21, and translocation trisomy 21 was found in nine
(2.5%) patients.
Epidemiology

17. About 95% of people
with Down syndrome
have Trisomy 21. With
this type of Down
syndrome, each cell in
the body has 3 separate
copies of chromosome 21
instead of the usual 2
copies
This type affects about
2% of the people with
Down syndrome Mosaic
means mixture or
combination. For children
with mosaic Down
syndrome, some of their
cells have 3 copies of
chromosome 21, but other
cells have the typical two
copies of chromosome 21.
Children with mosaic
Down syndrome may
have the same features as
other children with Down
syndrome
This type accounts for
a small percentage of
people with Down
syndrome (about 3%)
This occurs when an
extra part or a whole
extra chromosome 21
is present, but it is
attached or “trans-
located” to a different
chromosome rather
than being a separate
chromosome 21
Trisomy 21
(Chromosomal
nondisjunction)
Translocation
Down syndrome (Chromosomal
translocation)
Mosaic Down syndrome
(Chromosomal
nondisjunction)
Types of Down
Syndrome

18. Genetic Basis
1
2
3

19. Manifestation
 Short neck, with excess skin at the back of the
neck
 Flattened facial profile and nose
 Small head, ears, and mouth
 Upward slanting eyes with epicanthal fold
 White spots on the colored part of the eye
(called brush field spots)
 Wide, short hands with short fingers
 A single, deep crease across the palm of the
hand
 A deep groove between the first and second toes
 Developmental and intellectual impairment

20. Treatment
While there is no cure for Down syndrome,
a variety of treatment options and
interventions can significantly improve the
lives of individuals with this condition.
These interventions include:
 Therapy treatment
 Educational Support
 Medical Management
 Supportive services

21. Cancer
Cancer is a disease in which some of the body’s cells grow
uncontrollably and spread to other parts of the body. These cells
may form tumors, which are lumps of tissue. Tumors can be
cancerous or not cancerous (benign).
Cancerous tumors spread into, or invade, nearby tissues and can
travel to distant places in the body to form new tumors (a process
called metastasis). Cancerous tumors may also be called malignant
tumors. Many cancers form solid tumors, but cancers of the blood,
such as leukemias, generally do not.

22. Cancer
There are over 200 types of cancer; far too
numerous to list all. But below are the
general categories of some common ones
 Carcinoma
 Sarcoma
 Leukemia
 Lymphoma and Myeloma
 Central nervous system cancers etc.

23. There were 18.1 million new cases of cancer worldwide in 2020, it is
estimated. The four most common cancers occurring worldwide are
female breast, lung, bowel and prostate cancers.
The total number of new cases in Nigeria in 2020 was 124,815, of
which 51,398 occurred in males with prostate cancer as the commonest
at 29.8% and 73,417 occurred in females with breast cancer being the
commonest at 38.7%, followed by cancer of the cervix at 16.4%.
Epidemiology

24. Non hereditary
It is also called
acquired genetic
mutation and is
the cause of most
cancers. It occurs
in somatic cells.
It can be caused
by environmental
factors
Hereditary
They are rare and
can be passed to
offspring
because they
occur in germ
cells
NB
A single mutation typically
doesn't result in cancer.
According to the American
Cancer Society, it takes more
than one mutation in a cell for
cancer to occur. It actually takes
many mutations during a
person's lifetime to develop into
cancer.
Cancer is caused by changes (mutations) to the DNA within cells. There are two
types of these cancer causing genetic mutations:
Causes of Cancer

25. Genetic Basis
Mechanism
• Oncogene from mutation caused
excess production of CDK
• Inactivation (by mutation) of tumor
suppressor gene
Drivers: CDK and Cyclin
Regulator: Tumor Suppressor Gene
In the case of an abnormal cell or need for apoptosis, the
cell releases factors that causes tumor suppressor gene to
code for proteins which inactivates CDK, repairs the cell
or cause apoptosis as the case may be.

26. Manifestation
Manifestations of cancer will vary depending on
what part of the body is affected.
Some general signs and symptoms associated with,
but not specific to, cancer, include:
 Fatigue
 Lump
 Weight changes
 Skin changes, such as yellowing, darkening or
redness of the skin, sores that won't heal, or
changes to existing moles
 Changes in bowel or bladder habits
 Persistent cough or trouble breathing
 Difficulty swallowing
 Hoarseness
 Persistent indigestion etc.
Treatment
 Surgery:
 Chemotherapy:
 Radiation therapy
 Hormone therapy
 Immunotherapy
 Stem cell transplant (bone
marrow transplant)

27. Thank You