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Adv J Pharm Life sci Res, 2014 2;3:18-39 www.ajplronline.org

Advanced Journal of Pharmacie and Life science Research 18

INTRICATE ROLE OF GENE MUTATIONS IN VARIOUS DISEASE PATHOLOGY

Tapan Behl*, Ishneet Kaur, Heena Goel, Rajesh K Pandey

Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi

ABSTRACT

Genes being one of the most distinct characterizing features of every human being play a pivotal role

in shaping up the diverseness of an individual. They account for all the discrete attributes associated

with a particular person. Likewise, they are sometimes also responsible for some assorted unfortunate

events – the various types of known/unknown mutations occurring undesirably, which may either be

inherited or acquired, in certain genes – whose unfavourable consequences lead to some major

medical complications, which may or may not be cured. For most of them, medical science has no

current treatments and even those whose therapies are available, cannot be cured to an absolute level

because the treatments available for most of the genetic disorders, caused by such mutations, are not

adequate enough to rectify them unmitigated but compensate only by providing a mere solace in the

name of their management. This review, hereby, gives an account of four major disorders prevalent in

the present day world – namely Breast Cancer, Sickle Cell Anaemia, Alzheimer’s disease and Long

QT Syndrome (a type of Cardiac Arrhythmia), which are caused by the mutations occurring in some

specific genes. All these disorders pose a major threat – some to life itself and the rest to its quality,

thus arousing a prime obligation to understand the pathogenesis of these disorders and to find their

cure as soon as possible so as to save and capitalize certain precious lives, which otherwise would

surrender to their genetic fate and go in vain.

Keywords: Sickle cell anaemia; Presinilin-2; Transcription; Frame-shift mutations, C-terminus

INTRODUCTION

Genes are the basic units of

inheritance present on chromosomes – which

are the fragments of DNA (which comprises of

a number of nucleotides – containing a

nitrogenous base, a pentose sugar and a

phosphate group). They are responsible for the

expression of particular traits in an organism.

*Correspondence Address: Senior Research Fellow,

Department of Pharmacology, Vallabhbhai Patel Chest

Institute, University of Delhi, Delhi. Email:

[email protected]

There is a particular sequence in which the

nucleotides of DNA are arranged and this

sequence is responsible for their distinct

physiology.Any change in the sequence of

these nucleotides is termed as “mutation”.

Mutations have been the key mediators in the

evolution of life because a single mutation

causes many changes in the genotype and

phenotype of the organism [1].

But since every mutation that occurs

does not produces compatible results, with



time, there came into knowledge some of them

which cause many complications in living

beings, some of which are discussed later in

this context. A mutation may either be

inheritedby the offsrings from their parents

(such mutations are known as germline or

hereditary or inherited mutations because they

are passed on to the next generation by the

germ cells of the parents) or may occur in a

person during any point of his life due to

certain external factors (such as exposure to

UV radiations, X-rays or some toxic

chemicals) or internal copying mistake of

DNA within the cells during their division –

such mutations are known as acquired or

somatic mutations [2].

Involvement of Mutations in Various

Diseases

Since the synthesis of protein in the

body takes place through mRNA (by the

process of translation) whose formation

depends on DNA (by the process of

transcription), mutations in DNA account for

the dysfunctioning in the process of protein

synthesis. Mutations may either cause a

protein to function improperly or may even be

responsible for the complete absence of a

protein.

� Breast Cancer

Breast cancer is one of the topmost

malignant tumors which affect 10% of the

total women population in the Western

countries in their lifetime [4]. The tumor

originating from the breast cells account for

breast cancer. Its origin is from the inner lining

of the of the milk ducts (ductal carcinoma) or

the lobules which supply milk to the ducts

(lobular carcinoma) [5]. BRCA1 AND

BRCA2 are the two autosomal dominant genes

whose mutations have been linked to breast

cancer. They both are quite high penetrating

mutations. They may be both – either inherited

or acquired types of mutations. The risk of

developing breast cancer in women during

their lifetime with these two mutations is

approximately 60-85%, which is a quite high

figure, thus confirming the role of these two

mutations in the progression of this cancer [3,

6].

BRCA 1 Gene: This gene is found on the

chromosome 17q12-21. It is a quite large and

complex gene covering about 80 kb of the

DNA genome. It comprises of 22 coding

exons which are transcribed into 7.8 kb

mRNA which encodes a protein (which

consists of 1863 amino acid units). The N-

terminal end of the protein of BRCA1

comprises of a domain containing a zinc-

finger like projection which possesses cysteine

and histidine residues. This type of pattern is

also seen in many other proteins which

actively interact with DNA, thus speculating

that the protein of BRCA1 also performs a

similar activity [7-8]. Other than this, some

studies show that this terminus also interacts

with BARD1, BAP-1 and E2F-1 [9-11]. The

largest exon of the gene BRCA1 is the 11th

exon, which encodes about 60% of its protein.

It also contains sites of nuclear localization



signals. Some cellular proteins which both

directly and indirectly come and interactwith

this exon are RAD51, RAD50, p53, RB, c-

Myc[12-17]. The C-terminus is responsible for

the transcription activity of the BRCA1

protein and two domains of this terminal

interact with RNA polymerase II, p300/CBP,

BRCA2, RNA helicase and CtIp [18-19].

The mutations found in a study

conducted on the BRCA1 gene are 295delCA

(which includes two base pair deletions)

resulting in a frame shift mutation which leads

to formation of a ceasation in translation at

downstream codon 64. Another mutation

associated with this gene is 4213delT (or

L1365X) which includes the deletion of only

one base pair as compared to the previous one

which had two, again results in a frameshift

mutation. The consequence of this is that the

leucine codon at position 1365 converts to a

stop codon TAG. Third type of mutation found

in this gene is a transversion mutation of

52677 to G (Y1716X) which leads to the

tyrosine codon present at position 1716 to get

converted to a stop codon TAG. These four

mutations stated here were novel mutations

discoveredin a study conducted on south

Indian women. Thus the mutations reported

contained 3 deletion mutations which results

in the formation of a stop codon advance

downstream while three other were nonsense

mutations which lead to the generation of a

stop codon at the site of mutation. Other

mutations associated with this gene are – two

deletion mutations (185delAG and

3450delCAAG) and one transversion mutation

of 2983C to A. Out of all these mutations

which are reported till date, the mutation

which is found most commonly in Brca1 is the

185delAg mutation with a frequency of

16.4%, which is quite a high rate of occurring

of any mutation as compared to others. This

mutation was also reportedly the most

common mutation observed in cases studied in

Ashkenazi Jews population with an occurring

rate of about 18% in families associated with

the history of breast/ovarian cancer and 1%

among the normal population (i.e., which are

not exposed to these cancers in their family

history) [20-22].

BRCA2 Gene: This gene is even bigger in size

than BRCA1. It has 10.3 kb frame [23]. It

comprises of 27 exons and encodes a protein

which is a polypeptide of 3814 amino acids

[24]. The region near the C-terminus of this

protein possesses six amino acids features for

the domain of granin but the distinctive feature

is that it does not possess any hydrophobic

signal sequence. Another domain discovered

in this protein is the region where exon 11 is

present. It contains eight similar sequences of

20-30 amino acids which are named as BRC

motif separated by 60-300 amino acids in

between but the function of these BRC motifs

is yet unknown [25]. Another portion of the

protein occupied by third exon has got a

similar description as that of a well-known

transcription factor which is known to activate

transcription, thus suggesting that transcription

activation might be one of the functions of the

protein present in BRCA2. This region being



well conserved resembles some similarity in

terms of the sequence for the activation

domain of c-jun. Studies done on the activities

of transcription have shown that this region

might prove useful in the activation of

transcriptions when fused to GAL4 DNA-

binding domain [26]. Besides these, at the N-

terminal end also contains two interaction

sites. Moreover, in a study a strong activity of

HAT (Histone Acetyl Transferase) was

observed at this end of the protein. This part is

encoded by exon 3 of this protein and is

performs the transactivation function. Since

this is not needed for the activity of HAT, it is

suspected that it might be enabling another

functional domain of BRCA2 protein. This

study also showed that BRCA2 protein is

responsible for the acetylation of the H3 and

H4 fractions of the free histones, thus giving

rise to the speculations that this HAT activity

of BRCA2 might play a vital role in the tumor

suppression [27].

Like the mutation spectra of BRCA1,

the one associated with BRCA2 also contains

a wide variety of mutations deletions and

insertions type of mutations which lead to

frameshift and non-sense mutations in the

BRCA2 gene. The deletion mutations

discovered in this gene are 6174delT and

999del5, which constitue about 33% of the

cases of the germline mutations observed in

BRCA2. The former mutation is found in

about 8% of the cases observed in Ashkenazi

Jewish population where the onset of breast

cancer was early while the latter one was

found in the cases observed in Iceland having

hereditary early onset of this cancer. Also, an

observation made in the cases of Iceland was

that since all the cases of BRCA2 observed

were hereditary, only a single mutation in this

gene in their lifetime was enough for the onset

of breast cancer [28-30]. Other two mutations

identified in BRCA2 gene are – a deletion

mutation 6079delAGTT, which is associated

with the deletion of four-base pairs and an

insertion mutation in which one base pair

insertion takes place – 4866insT. This

insertion mutation was discovered in a study

conducted on Indian women of south origin. In

this mutation, an aspartic acid codon (GAT)

was observed to get converted into a stop

codon TGA at position 1547 (D1547X) [22].

Thus, people having above discussed

mutations become the susceptible hosts for

various carcinogens which when act upon

them lead to the progression of this cancer

[31-32]. Gene mutation leading to progression

of breast cancer is shown in Figure 1.

� Sickle Cell Anemia

Sickle cell anemia is a hereditary

hematopoietic disorder in which a single

mutation in the gene of hemoglobin molecule

of the RBCs leads to serious deformities in its

structure as well as functioning. The mutation

which occurs in this disorder results in

shortened life of the patient owing to the

attributes of the abnormal (or specifically

“sickled”) RBCs produced in them. According

to a survey conducted in the United States in

1994, the average life of the patients having

sickle cell anemia was reported to be 42 years



(in men) and 48 years (in women) [33]. The

inheritance pattern of this disorder is recessive

autosomal i.e., it is necessary for that each of

the copy of the genes being passed on to their

off-springs by the parents to be defective in

order to acclaim this disorder. Such off-springs

are known as homozygous people. The cases

where the off-springs inherit only one

defective copy of this gene are called

heterozygous or sickle cell traits because they

may pass on this defective copy of the gene

further to their next generation [34].

The molecule of hemoglobin A (which

makes up about 96% of the total hemoglobin)

comprises of four protein subunits comprising

of two alpha and beta chains each. Sickle cell

anemia is caused due to a point mutation in the

beta-globin gene which is present on

chromosome 11. The mutation results in the

replacement of a nucleic acid – glutamic acid

with another nucleic acid – valine at the 6th

codon of the protein chain [35].

The result of its hydrophobicity is the

aggregation of the haemoglobin molecule

which disfigures the RBCs. The ultimate fate

of this alteration is the loss of elastic nature of

the membrane of the red blood cells. After

deoxygenation, the normal RBCs have the

property to regain back their shape once they

get oxygenated again but the cells affected by

this mutation do not show this property. Once

they become sickle shaped on deoxygenation

they cannot regenerate their biconcave shape

even after sufficient oxygenation, due to lost

elasticity. This altered structure of hemoglobin

is called sickle hemoglobin (denoted by HbS).

Progression of sickle cell anaemia is shown in

Figure 2.

The following comparison between the normal

and sickled RBCs is presented [35-36]: -

Normal Gene

Mutated gene

Codon GAG GTG

Transcription GAG on mRNA GUG on mRNA

Translation

Anticodon CUC and amino acid glutamic acid on tRNA.

Anticodon CAC and amino acid valine on tRNA.

Hemoglobin HbA HbS

Shape Biconcave shaped red blood cells.

Sickle cell shaped red blood cells.

After the formation of HbS, major changes

take place in the body due to the property of

polymerization exhibited by it. When

deoxygenated, HbS turn into fibre-like

structures which aggregate forming polymers

via the process of homogenous nucleation

[37]. The growth of these fibres result in some

serious complications, out of which the two

most adverse consequences are:

• Progression of hemolyticanemia: -

Premature breakdown of the sickled red

blood cells is the primary reason for

causing anemia. The sickled cells die

before the normal life period (120 days) of

the erythrocytes. Further if such patients

also have the deficiency of G6PD

(glucose-6-phosphate dehydrogenase), the



situations get worse. Even though the bone

marrow tries to compensate the initial loss

of the blood cells by fastening the process

of erythropoiesis but it could not match-up

up the rate of hemolysis, thus accounting

for hemolyticanemia. The proofs of this

speculation are – the occurrence of bone-

marrow erythroid hyperplasia,

reticulocytosis, circuitous

hyperbilirubinemia and increase in

hemoglobin level and serum lactic acid

dehydrogenase levels in the plasma. [38-

39].

• Vaso-occlusion: - Some studies show that

the sickled red blood cells have a high

ability to adhere to the vascular

endothelial cells even when their least

dense population is present in the blood.

Further adverse conditions arise when

their population is increased. Their

adherence becomes to the endothelium

becomes greater with increase in their

population density. Due to their shape,

rigidity and non-deformable nature, the

sickled cells result in the blockage of

small capillaries leading to ischemia and

infarction. Also the obstruction caused by

these cells in microvasculature lead to

pain, tissue damage and necrosis of the

cells of blood vessels. The ischemia

caused due to such conditions becomes the

cause of some serious medical

complications such as stroke, kidney

failure and heart failure. Hypertension is

another problem caused due to the

narrowing of blood vessels [40-43].

Thus, the mutation is the precursor of a

variety of medical disorders which occur

as a result of the progression of sickle cell

anemia. Devastating consequences of

mutation is shown in the Figure 3.

� Alzheimer’s Disease

Alzheimer’s disease is a major disorder of the

central nervous system which is characterized

by diminished and in later stages completely

impaired intellects of a person accompanied

by mood or behavioral changes, long-term

memory loss, loss of the knowledge of

language and ultimately, inability of the

person to perform his own daily tasks. It is the

most common form of dementia (diseases

which affect the intellectual functions i.e., the

ability of thinking and reasoning). It usually

occurs after the age of 65 but recently another

form of this disease was also confirmed –

called early onset Alzheimer’s disease which,

as its name suggests, occurs before the age of

65 [44-47]. The manner of inheritance of

Alzheimer’ disease is autosomal dominant

(i.e., one inherited copy of the infected gene is

sufficient for the evolution of this diseaseand

the pattern of its occurrence observed in a

study was highly irregular and isolated in

various groups [48].

Two most characteristic lesions which are

typically associated with Alzheimer’s disease

are:-

• Neuritic plaques: - It consists of spherical

deposits of a molecule – beta amyloid



(which is an insoluble fragment of

amyloid precursor protein) – which forms

a dense core at the center and it is

surrounded by the neurons affected by this

disease. Also present at the periphery of

these spherical structures are the

microglial cells and astrocytes. These are

formed in the gray matter of the human

brain. They generally range from 20-200

micrometers in size.

• Neurofibrillary tangles: - These are

composed or paired helical besides some

straight filaments whose primary

component is an abnormally

hyperphosphorylated form of an axonal

microtubule protein tau, whose basic

function is the enhancement of the

assemblies of microtubules. They are

insoluble fragments and are hard to clear

in vivo, thus appear as “ghost” or the

“tombstone” of the dead neuron from

where they originated [49-50].

There are typically four such genes in

which the occurrence of mutation leads to

the progression of Alzheimer’s disease.

These mutations act as the basic

precursors in the pathophysiology of this

disease which makes the host susceptible

for the formation of above discussed

lesions:-

� PS-1 gene: - PS-1 (or Presenilin-1) gene is

responsible for the formation of a protein

called presenilin-1, which is an element of

a complex enzyme – gamma secretase,

whose major function is proteolysis (a

process by which a protein is cleaved into

smaller fragments). This gene is located

on chromosome 14. It consists of 13

exons, out of which the coding sequence is

encompassed on 10 of them.Various

researches have delineated 40 different

mutations in this gene. All these mutations

which are reported till date in presenilin-1

gene are missense mutations. The

mutations of this gene have been seen to

cause the early onset Alzheimer’ disease.

The explanation for the causes behind this

has been that the various mutations in this

gene interfere in the proteolysis performed

by gamma-secretase, which is an

important event which includes cleavage

of Notch in the Notch signaling pathway

which is a vital part in the cell signaling

pathways and transcriptional regulation of

the cells involved and accounts for the

transmission of signals from outside the

cell into the nucleus. Besides, the gamma-

secretase also accounts for the proteolysis

of amyloid precursor protein, cleaving it

into soluble fragments. But certain

mutations caused in this gene lead to

alterations in this proteolyticprocess such

that insoluble, long and neurotoxic

fragments of amyloid-beta peptides are

generated at the end of cleavage process,

thus accounting for its accumulation and

then subsequently leading to the formation

of lesions discussed above[49-55].



� PS-2 gene: - PS-2 (or presenilin-2) geneis

responsible for the formation of a protein

called presinilin-2, which is an important

component that processes the amyloid

precursor protein. It is located on

chromosome 1. Some studies suggest that

it helps other proteins in the process of

proteolysis of amyloid precursor proteins

into soluble fragments. Till date, 11

different mutations have been reported for

this gene by various researchers and these

all are missense mutations but out of these

only two are the most common mutations

observed in maximum cases in which the

early onset Alzheimer’s disease is caused

by PS-2 mutations. These two mutations

are – Asn141Ile or N141I (in which the

amino acid asparagine is replaced by the

amino acid isoleucine at the position 141)

and Met239Val or M239V (in which the

amino acid methionine is replaced by the

amino acid valine at the position 239).

Structurally, this gene is very similar to

PS-1 gene. This gene has been reported to

play a part in the growth and maturation of

the cell because it helps in the processing

of such proteins which carry out

transmission of chemical signals which are

responsible for the cell growth. The

mutations in this gene result in the

disruption of these processes as well as

affect the proteolysis of amyloid precursor

protein, as a result of which toxic amyloid-

beta peptides are formed which directs the

formation of neuritic plaques and

ultimately lead to death of the neurons

associated [56-60].

� APOE gene: - APOE is responsible for

the formation of a protein called

apolipoprotein E, whose main function is

to get bind to the lipids of the body (for

the formation of lipoprotein molecules)

and help in the transportation of

cholesterol and fats in the body. It is

located on chromosome 19. Specifically,

apolipoprotein E constitutes an important

part of very-low density lipoproteins

(VLDLs), which are responsible for the

transportation of the excess cholesterol

present in the body to the liver where it is

processed. This is an important process in

maintaining the normal physiology of the

body. Thus, any mutations in this gene

would cause serious problems because of

the disruption in the normal working of

VLDLs and would ulitimately result in

many complications like atherosclerosis,

various other blood vessel and heart

disorders and stroke. Three different

alleles (variants) found of APOE gene are

e2, e3 and e4. The allele related to

Alzheimer’s disease is e4. People who

have inherited this allele are considered in

the most-risked populations for the

progression of this disease. The

pathophysiology of ALOE-e4 in the

development of Alzheimer’s disease is

still unknown and is an area of active

research, but it has surely been associated

with the presence of neuritic plaques



(which are caused due to the accumulation

of toxic amyloid-beta peptides) which lead

to fatal damage to the neurons [59-65].

Although, a study concluded a decrease in

the age of onset of Alzheimer’s disease

with the increased dosage of APOEe4

gene, it cannot solely be responsible for

the onset of this disease. It is surely a risk

factor for it but is not sufficient enough

itself to mark the commencement of the

full-fledged disease [66-67]. Two another

studies separately found that there was no

link between the presence of APOEe4

genotype and the age-related progression

of Alzheimer’s disease in affected by

mutations of PS-1 while the possibility of

some weak associations of the same was

not ruled out in PS-2 families [68-69].

� APP gene: - The APP (amyloid precursor

protein) gene is responsible for the

formation of a amyloid precursor protein.

This protein is widely found in the tissues

of the brain. Although not much is known

about the functions of this protein in the

central nervous system, it is speculated

that it helps in the migration of neurons

during early period of development. This

gene is located on chromosome 21. A

mutation T714I was reported in this gene

in a study.

The proteolysis of amyloid precursor

protein might occur in different ways

which leads to the formation of different

fragments – two of which are- soluble

amyloid precursor protein (sAPP), which

is non-neurotoxic and is also speculated to

have role in the growth of the neurons and

amyloid-beta peptide, which is somewhat

neurotoxic and lead to the formation of

neuritic plaques. The effects of various

mutations which occur in this gene as well

as the genes dicussed above lead to the

formation of this peptide which is

responsible for damaging the neurons [49,

56, 59, 70-73]. Occurrence of cleavage of

beta-secratase cleavage is shown in Figure

4.

The beta-secretase cleavage occurs as

follows as shown in Figure 5.

This beta-secretase cleavage leads to the

formation of amyloid-beta peptide which

are noxious in the following manner as

shown in Figure 6.

� Long QT Syndrome (a type of Cardiac

Arrhythmia)

Cardiac Arrhythmia is a cardiac

disorder in which in which the normal rhythm

of the heart is disrupted. The normal rhythm of

the heart, also known as normal sinus rhythm,

originates from the sino-atrial or sinus node. It

has got a unique property of autorhythmicity,

which maintains the rhythm of the heart beats

of the human heart. Arrhythmia results from

any condition which causes alterations in

maintenance of this auto-rhythmicity. The

normal sinus rhythm when traced on a

electrocardiograph, gives the following pattern

which is known as electrocardiogram. Normal

electrocardiogram which lasts for 0.8 sec as

shown in Figure 7.



Long QT syndrome is a hereditary disorder in

which an increase in heartbeat is observed

owing to prolonged duration of ventricular

action potential and delayed repolarisation

phase. As its name itself suggests, this

syndrome is characterized by elongation of the

QT segment. In general, increased length of

the interval Q-T is a sign of myocardial

damage, myocardial ischemia (decreased

blood supply to heat muscle), or abnormalities

in the conductivity of the heart. Long QT

syndrome causes tachycardia (with chaotic

heartbeats), which may trigger sudden fainting

or even seizures.

Two form of long QT syndrome are

found normally, which are – Romano-Ward

syndrome (whose pattern of inheritance is as a

dominant autosomal trait) and Lange-Nielson

syndrome (whose pattern of inheritance is as a

recessive autosomal trait). Out of these two,

the former one is more common and is not

associated with any other phenotypic

abnormality unlike the latter which is usually

associated with deafness. Various mutations

which have been held responsible for this

syndrome which are found on various genes

(e.g., KVLQT1, HERG, SCN5A,

KCNE1,KCNE2 etc.) and are enlisted below: -

• LQT1:- This type of mutation is found on

the gene KCNQ1, which is an alpha

subunit of voltage gated potassium

channel. This gene is located on

chromosome 11 at position 15.5-15.4. This

is the most common type of mutation

found in most cases of long QT syndrome.

This gene is responsible for the proper

functioninf of potassium channels which

send potassium ions out of the cell. The

mutations (such as A46T, Y51X, P73T,

etc)in this gene cause the reduction in the

amount of repolarizing current, which is

essential for ceasing the action potential.

Thus, this reduction causes a prolonged

duration of the action potential.


the gene HERG (also known as KCNH2),

which is an alpha subunit of voltage gated

potassium channel. This gene is located on

the chromosome 7 at position 36.1. This

gene has an immensely important function

of conducting the potassium ions out of

the cardiac muscle cells so as to correctly

time the repolarization phase of the action

potential. People having mutations (such

as S26I, F29L, Y43C, C44X, S55L, etc) in

this gene are at a great risk of sudden

death due to absence of the some functions

performed by HERG (particularly

suppressing the irregular extra beats).


a gene- SCN5A, which is an alpha subunit

of sodium channel. This gene is located on

chromosome 3 at position 22.2. The gene

SCN5A is said to be responsible for the

initial trigger of the action potential, which

is the rapid repolarization state. Various

missense mutations (such as L404Q,

R18W, V125L, S216L, Q245K, N406K,

A413T etc) which commonly occur on this



gene renders the channel gatein a state of

partial inactivation, thus causing the

triggering of a number of action potentials

one after the other abruptly. This state

occurs after prolonged depolarization

caused due to the defects in the cycle of

action potential.


the gene ANK2, which codes for a protein

called Ankyrin B whose main function is

anchoring of ion channels. This gene is

located on the chromosome 4 at position

25-26. The Ankyrin B protein is required

in the body to maintain the integrity of

plasma membrane of the cells and the ion

channels present on it. The mutations

(such as E1425G, 106410.0001) in this

gene results in bradycardia (due to the

prolongation of action potential), delayed

conduction or blackage in conduction (due

to lost integrity of cellular structure).

These types of events generally occur

during rest or sleep.


the gene KCNE1, which codes for a

protein called KCNE1 (also known as

MINK protein) whose function is to

regulate the activity of potassium

channels. This gene is found on the

chromosome 21 at position 22.1-22.2. The

normal regulation of the potassium

channels by this protein helps in the efflux

of potassium ions from the cell. Three

mutants – namely V47F, W87R and D76N

and five mutations – namely T7I, T59P,

L60P, S74L and D76N were found to

affect this gene by altering the potassium

channel activity and thus resulting in

reduced amplitudes of the action potential

thus prolonging its duration [74-78].

Schematic representation of mutation in

the gene KCNE1 shown in Figure 8.

CONCLUSION

After mentioning all the facts related

to mutations which lead to the progression of

various above given diseases, we conclude that

mutations, indeed, are the central cause of the

emergence of the various changes which occur

in a cell and play the most pivotal role in the

pathophysiology of the genetic disorders.

Since one has no control over such events

occurring in their cells, the victims become

mere innocent preys to their fates decided by

such mutations. Since no proper treatment of

such disorders is available with medical

science till now, there is an urgent need for

developing methods which could help

reversing the mutations or at least their effects.

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