CENTRAL LUZON DOCTORS’ HOSPITAL

EDUCATIONAL INSTITUTION, INC.

Romulo Highway, San Pablo, Tarlac City
Tel No. (045) 982-5019/982-5052/982-0264 Fax No. (045) 982-0780/982-2757

Department of Medical Technology

Prepared by:
Kristelle B. Bansil, RMT, MLS (ASCPi)CM
Genetic Disease
Nature of Genetic Abnormalities Contributing to Human Disease

Mutation
- Refers to permanent changes in the DNA of the cell. Those that affect germ cells are
transmitted to the progeny and may give rise to inherited disease.
- Mutation in somatic cells are not transmitted to progeny but are important in the
causation of cancers and some congenital malformations.
Examples of gene mutations and their effects:
• Point mutations- results from the substitution of a single nucleotide base by a different
base, resulting in replacement of one amino acid by another in the protein product
• Frameshift mutations- occurs when the insertion or deletion of one or two base pairs
alters the reading frame of the DNA strand
• Trinucleotide repeat mutations-characterized by amplification of a sequence of three
nucleotides. Example of this is the fragile X syndrome in which there are 200 to 4000
tandem repeats of the sequence CGG within a gene called FMR1
Three major categories of genetic disorders:
• Mendelian disorders resulting from mutations in single genes
- The genetic abnormalities show high penetrance, meaning the most individuals who
inherit the anomaly show phenotypic effects
- Hereditary familial
- They include many uncommon conditions, such as storage diseases and inborn errors
of metabolism
Important Examples of Mendelian Disorders (Single Gene Defects)
I. Autosomal Recessive Inheritance
1. β-thalassemia
2. Sickle cell anemia
3. Haemochromatosis
4. Cystic fibrosis of pancreas
5. Albinism
6. Wilson’s disease
7. Xeroderma pigmentosum
8. Inborn error of metabolism (Lysosomal storage diseases, glycogenosis,
alkaptonuria, phenylketonuria)
II. Autosomal Codominant Inheritance
1. ABO blood group system
2. α1-antitrypsin deficiency
3. HLA antigens
III. Autosomal Dominant Inheritance
1. Familial polyposis coli
2. Adult polycystic kidney
3. Hereditary spherocytosis
 4. Neurofibromatosis (von Recklinghausen;s disease)
5. Marfan’s syndrome
6. Von Willebrand’s disease
7. Hereditary hemorrhagic telangiectasia
8. Acute intermittent porphyria
9. Familial hypercholesterolemia
10. Osteogenesis imperfecta
IV. Sex-(X-)- Linked Recessive Inheritance
1. Hemophilia A
2. G6PD deficiency
3. Diabetes insipidus
4. Chronic granulomatous disease
5. Color blindness
6. Bruton’s agammaglobulinemia
7. Muscular dystrophies
V. Sex-(X-) - Linked Dominant Inheritance
1. Hypophosphatemic rickets
2. Incontinentia pigmenti
• Complex disorders involving multiple genes as well as environmental influences
(Multifactorial influences/Inheritance)
- Disorders which result from the combination of genetic composition and
environmental influences.
- Some of the most common disorders of mankind, including cleft lip and cleft palate,
Pyloric stenosis, Diabetes mellitus, Hypertension, Congenital heart disease and
Coronary heart disease
• Diseases arising from chromosomal abnormalities, including changes in the number
or structure of chromosomes.
• Other genetic diseases, which involve single gene mutations but do not follow
mendelian rules of inheritance.
- Single gene disorders with non-classic inheritance patterns. Example of this are those
resulting from triplet repeat mutations or from mutations in mitochondrial DNA, and
those in which the transmission is influenced by genomic imprinting

References:
Robbins Basic Pathology 10th ed.
Textbook of Pathology by Harsh Mohan