diseases that result from
gene mutations
Huntington’s Disease Dominant
Autosomal No group association
• Caused by a trinucleotide repeat expansion in the gene coding for Huntingtin (Htt).
• This expansion produces an altered form of the Htt protein, mutant Huntingtin (mHtt), which results in
neuronal cell death in select areas of the brain.
• Most people with HD eventually exhibit jerky, random, uncontrollable movements called chorea.
• Initially exhibited as general lack of coordination and an unsteady gait and gradually increase as the
disease progresses; this eventually causes problems with loss of facial expression or exaggerated facial
gestures, inability to sit or stand stably, speech, chewing and swallowing.
• Huntington's disease is a terminal illness.
• Pre-symptomatic testing is possible by means counting the number of repetitions in the gene.
• A negative test means that the individual does not carry the expanded copy of the gene, will never
develop symptoms, and cannot pass it on to children. A positive blood test means that the individual does
carry the expanded copy of the gene, will develop the disease, and has a 50% chance of passing it on to
children.
• A pre-symptomatic positive test is not considered a diagnosis, because it may be decades before onset.
• There is no treatment to fully arrest the progression of the disease, but symptoms can be reduced or
alleviated through the use of medication and care methods.
Recessive / Codominant
Sickle Cell Disorder
A heterozygous individual who does not have the disease
still retains immunity to malaria.
Occurs more commonly in people (or their descendants)
Autosomal
from parts of the world such as sub-Saharan Africa
• The normal Hgb gene is mutated to Hgb S or Hb S.
• Caused by a point mutation in one of the polypeptide chains of hemoglobin, replacing the amino acid
glutamic acid with the less polar amino acid valine.
• In many forms of the disease, the red blood cells change shape upon deoxygenation; the hemoglobin
proteins stick to each other, causing the cell to get a rigid surface and sickle shape.
• This process damages the red blood cell membrane, and can cause the cells to become stuck in blood
vessels. This deprives the downstream tissues of oxygen and causes ischemia and infarction, which may
cause organ damage, such as stroke.
• The disease is chronic and lifelong. Individuals are most often well, but their lives are punctuated by
periodic painful attacks. Life-expectancy is shortened
• Detection is possible by a Sickle Solubility test. A mixture of hemoglobin S (Hb S) in a solution gives a
turbid appearance while normal Hb gives a clear solution.
• Abnormal hemoglobin forms can be detected on hemoglobin electrophoresis, a form of gel
electrophoresis on which the various types of hemoglobin move at varying speed.
• Those with one or two alleles of the sickle cell disease are resistant to malaria since the red blood cells
are not conducive to the parasites.
Recessive
Cystic Fibrosis (CF)
It is most common among Europeans and Ashkenazi
Autosomal
Jews.
• CF is caused by a mutation in a gene called the cystic fibrosis transmembrane conductance regulator
(CFTR).
• The product of this gene is a chloride ion channel important in creating sweat, digestive juices, and
mucus.
• In its most common form, is a deletion of a single codon, resulting in the absence of one amino acid from
the resulting polypeptide chain.
• Difficulty breathing and insufficient enzyme production in the pancreas are the most common symptoms.
Thick mucus production, as well as a less competent immune system, results in frequent lung infections
• Individuals with cystic fibrosis can be diagnosed prior to birth by genetic testing.
• In early childhood a sweat test analyzed for abnormal amounts of sodium and chloride.
• There is no cure for CF, and most individuals with cystic fibrosis die young: many in their 20s and 30s
from lung failure.
Incompletely Dominant
In heterozygous FH, only one of the two DNA copies
Familial Hypercholesterolemia (FH)
(alleles) is damaged, and there will be at least 50% of the
normal LDL receptor activity (the "healthy" copy and
whatever the "broken" copy can still contribute).
Autosomal No group association
• FH is caused by defects in LDL-Receptor gene resulting in the absence or grossly malfunctioning low-
density lipoprotein (LDL) receptors.
• Characterized by very high LDL cholesterol and early cardiovascular disease running in families.
• Many FH patients develop accelerated atherosclerosis due to the excess LDL.
• The degree of atherosclerosis roughly depends of the amount of LDL receptors still expressed by the cells
in the body and the functionality of these receptors.
• LDL-receptor gene defects can be identified with genetic testing.
Phenylketonuria (PKU) Recessive
Autosomal No group association
• Characterized by a deficiency in the enzyme phenylalanine hydroxylase (PAH).
• This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine.
• Left untreated, this condition can cause problems with brain development, leading to progressive mental
retardation and seizures.
• When PAH is deficient, phenylalanine accumulates and is converted into phenylketones, which are
detected in the urine
• PKU is normally detected using the HPLC (High performance liquid chromatography) test.
• PKU is one of the few genetic diseases that can be controlled by diet. A diet low in phenylalanine and
high in tyrosine can bring about a nearly total cure.
• This requires severely restricting or eliminating foods high in phenylalanine, such as breast milk, meat,
chicken, fish, nuts, cheese and other dairy products. Starchy foods such as potatoes, bread, pasta, and
corn must be monitored. Many diet foods and diet soft drinks that contain the sweetener aspartame must
also be avoided.
Tay Sachs Disease Recessive
Increased prevalence in the Eastern European Jewish
Autosomal (Ashkenazi), and French Canadians of southeastern
Quebec.
• Caused by mutations on the HEXA gene
• The condition is caused by insufficient activity of an enzyme called hexosaminidase A that catalyzes the
biodegradation of fatty acid derivatives known as gangliosides.
• When Hexasaminidase A is no longer functioning properly, the lipids accumulate in the brain and cause
problems
• The disease occurs when harmful quantities of a fatty acid derivative called a ganglioside accumulate in
the nerve cells of the brain.
• Infantile TSD. Infants with Tay-Sachs disease appear to develop normally for the first six months of life.
Then, as nerve cells become distended with gangliosides, a relentless deterioration of mental and
physical abilities occurs. The child becomes blind, deaf, and unable to swallow. Muscles begin to atrophy
and paralysis sets in. Death usually occurs before the age of 4 or 5.
• Juvenile TSD. Extremely rare, Juvenile Tay-Sachs disease usually presents itself in children between 2
and 10 years of age. They develop cognitive, motor, speech difficulties (dysarthria), swallowing difficulties
(dysphagia), unsteadiness of gait (ataxia), and spasticity. Patients with Juvenile TSD usually die between
5–15 years.
• Adult/Late Onset TSD. A rare form of the disorder, known as Adult Onset Tay-Sachs disease or Late
Onset Tay-Sachs disease (LOTS), occurs in patients in their 20s and early 30s. It is characterized by
unsteadiness of gait and progressive neurological deterioration.
• An inexpensive automated, enzyme assay test (screening for enzyme activity) was developed providing
one of the first "mass screening" tools in medical genetics.
• All patients with Tay-Sachs disease have a "cherry-red" spot, easily observable by a physician using an
ophthalmoscope, in the back of their eyes (the retina).
• Several options for gene therapy have been explored for Tay-Sachs
• Fatal in its most common variant known as Infantile Tay-Sachs disease
Hemophilia Recessive
Sex linked (X) No group association
• In the most common form, hemophilia A, clotting factor VIII is absent.
• As with all genetic disorders, it is of course also possible for a human to acquire it spontaneously through
mutation, rather than inheriting it, because of a new mutation in one of their parents' gametes.
• Hemophilia impairs the body's ability to control blood clotting, or coagulation.
• When a blood vessel is injured, a temporary scab does form, but the missing coagulation factors prevent
fibrin formation which is necessary to maintain the blood clot. Thus a hemophiliac does not bleed more
intensely than a normal person, but for a much longer amount of time.
• In severe hemophiliacs even a minor injury could result in blood loss lasting days, weeks, or not ever
healing completely.
• Genetic testing and genetic counseling is recommended for families with haemophilia.
• Prenatal testing, such as amniocentesis, is available to pregnant women who may be carriers of the
condition.
• Blood Screening can be used to test for the presence of the disorder.
• Though there is no cure for haemophilia, it can be controlled with regular infusions of the deficient clotting
factor.
• Hemophiliacs can lead lives that are almost normal. Their life expectancy does not differ greatly from that
of an ordinary person, provided that proper treatment is available.
• The effects of this sex-linked, X chromosome disorder are manifested almost entirely in males.
Albinism Recessive
Autosomal No group association
• Albinism type 1 is caused by an alteration of the tyrosinase gene.
• Albinism type 2, the most common type of albinism, is caused by mutation of the P gene which encodes
a protein that is associated with melanosomal membranes
• The principal gene which results in albinism prevents the body from making the usual amounts of the
pigment melanin.
• Most humans and many animals with albinism appear white or very pale.
• The eyes of an animal with albinism occasionally appear red due to the underlying retinal blood vessels
showing through where there is not enough pigment to cover them.
• People with Albinism type 2 generally have more pigment and better vision than those with Type 1, but
cannot tan. A little pigment can develop in freckles or moles. People with Type 2 usually have fair skin
but not as pale as Type 1, and pale blonde to golden or reddish-blonde hair, and most commonly blue
eyes.
• Genetic testing can confirm albinism and what variety it is, but offers no medical benefits.
• The albinistic are generally as healthy as the rest of their species, with growth and development occurring
as normal, and albinism by itself does not cause mortality.
• It is vital that people with albinism use sunscreen when exposed to sunlight to prevent premature skin
aging or skin cancer
• Due to albinism's effect on one's outward appearance, cultures around the world have developed many
superstitions regarding people with albinism
Achondroplasia Dominant
Autosomal No group association
• Achondroplasia is a result of a mutation in the fibroblast growth factor receptor gene 3 (FGFR3), which
causes an abnormality of cartilage formation and this leads to severely shortened bones.
• People with achondroplasia have one normal copy of the fibroblast growth factor receptor 3 gene and one
mutant copy (They are heterozygous).
• Achondroplasia is a common cause of dwarfism. Achondroplastic dwarfs have short stature, with an
average adult height of about just over 4 feet.
• One result of the low muscle tone associated with Achondroplasia is that walking doesn't occur until
between 24 and 36 months.
• Because of short stature, obesity is often associated with the condition.
• Achondroplasia can be detected before birth by the use of prenatal ultrasound.
• A DNA test can be performed before birth to detect homozygosity, where two copies of the mutant gene
are inherited, a condition which is lethal and leads to stillbirths.
• Other indicators of achondroplasia include slow motor movement and low muscle tone (hypotonia).
• Growth hormone won't help people with achondroplasia.
• However, surgery of limb-lengthening will lengthen the legs and arms.
• Two copies of the mutant gene (the homozygous condition) are invariably fatal before, or shortly after
birth.
