DEPARTMENT OF MEDICAL TECHNOLOGY
INSTITUTE OF ARTS AND SCIENCES
FAR EASTERN UNIVERSITY
GENETIC DISORDER
Autosomal Dominant and Autosomal Recessive
GENETIC DISORDER
• Genetic disorder is a disease that is caused by an abnormality in an individual’s DNA.
• Range from a small mutation in DNA or addition or subtraction of an entire chromosome or set
of chromosomes.
• May result by point mutation or any insertion/ deletion entirely inside one gene
TYPES OF INHERITED DISEASE
1. AUTOSOMAL DISORDER
• Autosomal Dominant
• Autosomal Recessive
2. ALLOSOMAL DISORDER
• X-Linked Dominant
• X-Linked Recessive
• Y-Linked
3. MITOCHONDRIAL DISORDER
AUTOSOMAL DISORDERS
AUTOSOMES OR SOMATIC CHROMOSOMES
• carry genes that determine the somatic characteristics and do not have any influence on
determining the sex of the individual
• Appears in pairs
• Disorders related to Autosome are autosomal disorders
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TYPES OF AUTOSOMAL DISORDER
>AUTOSOMAL DOMINANT
• A pattern of inheritance in which an affected individual has one copy of a mutant gene
and one normal gene on a pair of autosomal chromosomes.
Achondroplasia
• Gene defect: Fibroblast growth factor receptor 3 (FGR3)
• Clinical Feature: Short limbs relative to trunk, prominent forehead, low nasal root, redundant
skin folds on arms and legs
Hypercholesterolemia
• Gene defect: LDL receptor
• Clinical Feature: Impaired uptake of LDL, elevated levels of LDL cholesterol, cardiovascular
disease and stroke. Symptoms more severe in homozygous individuals
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Holoproencephaly
• Gene defect: Sonic Hedgehog
• Clinical Feature: Malformation of the brain (no or reduced evidence of an interhemispheric
fissure), dysmorphic facial features, mental retardation
Huntington Disease (Huntington Chorea)
• Gene defect: Huntingtin (HD) – CAG repeat expansion within exon 1
• Clinical Feature: Disorder is characterized by progressive motor, cognitive and psychiatric
abnormalities. Chorea – nonrepetitive involuntary jerks – is observed in 90% of patients
Marfan Syndrome
• Gene defect: Fibrillin-1 gene (FBN1) encodes a microfibril-forming connective tissue protein
• Clinical Feature: Abnormalities of the skeleton (disproportionate tall stature, scoliosis), heart
(mitral valve prolapse, aortic dilatation, dissection of the ascending aorta), pulmonary system,
skin (excessive elasticity), and joints (hypermobility). A frequent cause of death is congestive
heart failure.
Myotonic Dystrophy
• Gene defect: A protein kinase gene (DMPK) – CTG repeat expansion in 3’ untranslated region of
the gene
• Clinical Feature: Disorder shows anticipation. Muscle weakness, cardiac arrhythmias, cataracts
and testicular atrophy in males. Children born with congenital form have a characteristic open
triangle-shaped mouth
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Neurofibromatosis I
• Gene defect: Microdeletion at 17q11.2 involving the NF1 gene
• Clinical Feature: The disorder is characterized by numerous benign tumors (neurofibromas) of
the peripheral nervous system, but a minority of patients also show increased incidence of
malignancy (neurofibrosarcoma, astrocytoma, Schwann cell cancers and childhood CML –
chronic myelogenous leukemia)
Osteogenesis Imperfecta
• the α1 or α2 chains of type I collagen
• Clinical Feature: Null mutations produce a milder form of the disease. Missense mutations that
act in a dominant negative manner are often perinatal lethal. The disorders are associated with
deformed, undermineralized bones that are subject to frequent fracture.
Polycystic Kidney Disease
• Gene defect: Mutations in either polycystin-1 (PKD1) or polycystin-2 (PKD2) gene
• Clinical Feature: Heterozygous individuals are predisposed to polycystic kidney disease because
they are likely to lose the second good copy of the gene during their lifetime. Multiple renal
cysts, blood in urine, end-stage renal disease and kidney failure.
>AUTOSOMAL RECESSIVE
• Two copies of an abnormal gene must be present in order for the disease or trait to
develop.
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Cystic Fibrosis
• Gene defect: Cystic fibrosis transmembrane regulator (CFTR) – impaired chloride ion channel
function
• Clinical Feature: Pancreatic insufficiency due to fibrotic lesions, obstruction of lungs due to thick
mucus, lung infections (Staph, aureus, Pseud. aeruginosa)
Gaucher’s Disease
• Gene defect: Β-Glucosidase
• Clinical Feature: Lysosomal storage disease characterized by splenomegaly,hepatomegaly, and
bone marrow infiltration. Neurological symptoms are not common
Hemochromatosis
• Gene defect: HFE gene on the short arm of chromosome 6 (C282Y mutation)
• Clinical Feature: Enhanced absorption of dietary iron with accumulation of abnormal,
pigmented, iron-protein aggregates (hemosiderin) in visceral organs.
• Cirrhosis, cardiomyopathy, diabetes, skin pigmentation, and arthritis.
Phenylketonuria
• Gene defect: Usually due to a mutation in Phenylananine hydroxylase (PAH)
• Clinical Feature: Mental retardation, if untreated, possibly due to inhibition of myelination and
disruption of neurotransmitter synthesis. Detectable by newborn screening and treatable
Tay-Sachs Disease
• Gene defect: Β-Hexosaminidase A isoenzyme (HEXA)
• Clinical Feature: Hypotonia, spasticity, seizures, blindness, death by age 2. An early indication is
a cherry red spot on the retina.
Xeroderma pigmentosum
• Gene defect: Anyone of nine genes involved in nucleotide excision repair (locus heterogeneity)
• Clinical Feature: Acute photosensitivity, premature skin aging, premalignant actinic keratoses,
and benign and malignant neoplasms of the skin, including basal cell carcinoma, squamous cell
carcinoma, or both. 5% of patients develop melanomas. Patients also exhibit ocular problems
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due to UV damage and have a 10- to 20-fold increased incidence of internal neoplasms due to an
inability to repair DNA damage by endogenously generated and environmental genotoxic agents.
