Simple and Complex Genetic Diseases

1
Simple and Complex Genetic Diseases

• Simple One gene -gt one disease
• Example sickle-cell anemia
• Complex Many genes interacting with
• other and the environment -gt one disease
• Examples MS, Types I, II diabetes

2
Single Gene Disorders

• Autosomal recessive
• Albinism
• Cystic fibrosis
• Phenylketonurea

3
Galactosemia

• Metabolic disorder defect in galactose
  meatbolism,
• The problem in the enzyme galactose 1- phoshate
  uridyl transferese, Which breakdown glucose.
• This leads to accumulation of galactose in blood,
  leads to blood poisoning which cause
• 1- Hepatomegaly
• 2- Cirrrhosis
• 3- Renal failure
• 4- Cataracts
• 5- Brain damage

4
Mucopolysaccharidosis

• Absence of lysosomal enzymes (a-L-iduronidase)
  which digest Mucopolysaccharide (also named
• Glycosaminoglycans)
• This sugar is found in the liquid between joints
  and act as lubricant.

5
Autosomal dominant

• Achondroplasia
• Askeletal disorder causeing dwarfism, shortening
  in limbs and digits, enlargement in skull.
• Caused as a defect in Fibroblast Growth factor
  Receptor Gene3 (FGFR3)
• This leads to a defect in cartilage and bone
  growth.

6
Marfan syndrome

• 15q 15-21
• Affect c.t
• Defect in FBN1 gene

7
Neurofibromatosis

• 17q11
• Swallow sacs under skin affect skin, bone and
  nerves
• Caused as a defect in the Neurofibromin gene.

8
Brachydactyly

• 5p13 and 2q33
• Problem in fingers
• Noonan syndrome
• Defect in PTPN11 gene which encode
• Protain Tyrosine Phosphatase, which play a role
  in embryonic development, Differentiation and
  migration

9
Huntington's disease

• 4p16
• Trinucleotide repeat expansion in the gene which
  encode Huntington protein.
• This leads to defect in the produced protein,
  degeneration in neurons, and chorea.

10
1 Glucose-6-ph. Dehydrogenase deficiency

• X-Linked r
• Deficiency in
• Glucose-6-ph. dehydrogenase enzyme
• ( G6PDH)
• This enzyme is related to Pentose phosphorylation
  Pathway
• This enzyme converts Glucose-6-ph to 6-
  Phosphogluconate delta-lactone

11
Duchenne muscular dystrophy

• Defect in the gene which encode Dystrophin
• Haemophilia A
• Defect in the gene which encode Factor VIII

12
Hypophosphatemia

• X-linked dominant disorders
• a form of vitamin D- resistant rickets

13
Y-linked genes

• Sex determining gene (SRY) encodes SDF which
  important in sex determination by playing a role
  in early stages of testis differentiation.
• Any defect cause XY female (Swyer syndrome)
• Translocation of part Y chromosome which contain
  SRY gene to X chromosome give XX male syndrome

14

• ANT3 (adenine nucleotide translocase)
• Produce enzyme change and transfer ADP from
  internal mitochondria to ouside as ATP

15
CSF2RA

• Colony stimulating factor 2 receptor a
• Produce cell surface receptor for growth factor
• Control production, differentiation of
  granulocytes and macrophages.

16
H-Y gene

• Plasma membrane protein
• Play a role in testis differentiation

17
ZFY

• Zinc finger protein
• DNA binding protein that regulate gene expression

18
Mitochondrial disorders

• Mitochondrial myopathy
• neurodegenerative disorder
• seizures, diabetes mellitus, hearing loss, short
  stature, and exercise intolerance are clearly
  part of the disorder.

19
MERRF syndrome

• muscular disorders
• cause a dysfunction of the brain and muscles
  (encephalomyopathies).

20

• The most characteristic symptom of MERRF syndrome
  is seizures that are usually sudden, brief,
  jerking, spasms that can affect the limbs or the
  entire body.
• Impairment of the ability to coordinate movements
  (ataxia), as well as an abnormal accumulation of
  lactic acid in the blood (lactic acidosis) may
  also be present in affected individuals.
• Difficulty speaking (dysarthria), optic atrophy,
  short stature, hearing loss, and involuntary
  jerking of the eyes (nystagmus)

21
Leigh syndrome

• progressive neurodegenerative disorder in one or
  more areas of the central nervous system,
  including the brainstem, thalamus, basal ganglia,
  cerebellum, and spinal cord.
• The lesions are areas of demyelination, gliosis,
  necrosis, spongiosis, or capillary proliferation.
  Clinical symptoms depend on which areas of the
  central nervous system are involved.
• The most common underlying cause is a defect in
  oxidative phosphorylation

22
Sideroblastic anemia

• abnormal production of RBCs which can evolve into
  leukemia.
• Thus, the body has iron available, but cannot
  incorporate it into hemoglobin
• The common feature of these causes is a failure
  to completely form heme- whose biosynthesis takes
  place partly in the mitochondria. This leads to
  deposits of iron in the mitochondria that form a
  ring around the nucleus of the developing RBCs.
  This leads to a stage in bone marrow disorder
  that leads to acute leukemia.

23
Myoclonus

• involuntary twitching of muscles.
• The myoclonic twitches or jerks are usually
  caused by sudden muscle contractions
  Contractions are called positive myoclonus
  relaxations are called negative myoclonus.
• myoclonic jerks are also a sign of a number of
  neurological disorders.
• Hiccups are also a kind of myoclonic jerk
  specifically affecting the diaphragum.

24

• myoclonus is one of several signs in a wide
  variety of nervous system disorders such as
  Parkinsons disease, Alzheimers disease, and
  some forms of epilepsy

25
Myopathies

• affect muscles connected to bones (called
  skeletal muscles), such as the biceps in the
  upper arm and the quadriceps in the thigh.
• Myopathies can be caused by inherited genetic
  defects (e.g., muscular dystrophies), and
  endocrine, inflammatory , and metabolic
  disorders.

26
Cardiomyopathy

• the heart muscle becomes inflamed and doesn't
  work as well as it should.
• There may be multiple causes including viral
  infections.
• Cardiomyopathy can be classified as primary or
  secondary.
• Primary cardiomyopathy can't be attributed to a
  specific cause, such as high blood pressure,
  heart valve disease, artery diseases or
  congenital heart defects.
• Secondary cardiomyopathy is due to specific
  causes. It's often associated with diseases
  involving other organs as well as the heart.

27
Renal tubular acidosis (RTA)

• is a disease that occurs when the kidneys fail to
  excrete acids into the urine, which causes a
  person's blood to remain too acidic.
• Without proper treatment, chronic acidity of the
  blood leads to growth retardation, kidney stones,
  bone disease, and progressive renal failure.
• The word acidosis refers to the tendency for RTA
  to lower the blood's pH. When the blood pH is
  below normal (7.35), this is called acidemia.
• Its causes are diverse, and its consequences can
  be serious, including coma and death.

28
Variation in chromosome number

• Trisomy 18 (47,XY,18) Edward
• Syndrome

29
Trisomy 18 Incidence 13333 live births Most
common abnormality in stillbirths with
multiple congenital abnormalities Prenatal
growth deficiency resulting in a small for
gestational age infant (SGA) 90 congenital
heart defect VSD 10 alive at one year
Marked developmental disability
30
Trisomy 18 -Physical Features

• Prominent occiput
• Micrognathia
• Microcephaly
• Low set malformed ears
• Characteristic clenched fists
• Rocker-bottom feet
• Short big toe that is dorsiflexed

31

• Trisomy 18 Edward Syndrome
• Trisomy 18
• Prominent Occiput
• Low-set malformed ears
• Small chin
• Clenched fists

32

• Trisomy 18
• Ocular manifestations in 10
• Low-arch dermal ridge pattern
• Underdeveloped nails
• Congenital anomalies of lungs,diaphragm, and
• kidneys
• Hernias, cryptorchidism, rectus muscle
  separation

33

• Trisomy 13 (47,XY,13) Patau
• Syndrome

34

• Trisomy 13
• Incidence 15,000 births
• Distinctive malformation pattern
• (Craniofacial and Central Nervous System)
• 95 spontaneously aborted
• Survival rate and development similar to
  Trisomy 18

35

• Trisomy 13 PatauSyndrome
• Microcephalywith sloping forehead
• Holoprosencephaly
• Ophthalmologic abnormalities microphthalmiaor
  anophthalmia Colobomataof iris and ciliarybody
• Cleft lip /-palate
• Low set ears with abnormal helices

36

• Trisomy 13 PatauSyndrome
• Cardiac defects ASD, PDA, VSD
• Males cryptorchidism Females
  Bicornuateuterus
• Polycystic kidneys
• Aplasiacutis congenita
• Polydactylyof hands /-feet
• Rockerbottomfeet

37
Turner syndrome

• SHORT STATURE
• OVARIAN DYSGENESIS
• INFERTILITY
• LEARNING DISABILITIES
• SPATIAL PERCEPTION

38
XXX females

• About one woman in 1000 has an extra X
  chromosome. It
• seems to do little harm, individuals are fertile
  and do not
• transmit the extra chromosome.

39
XYY males

• XYY males Incidence 1 in 1000 male births.
• May be without any symptoms. Males are tall but
  normally proportioned.

40

• Glu
• Ab 5i GTG CAC CTG ACT CCT GAG GAG AAG TCT O O O
  3i
• Sb 5i GTG CAC CTG ACT CCT GTG GAG AAG TCT O O O
  3i
• Val