Genetic diseases

MUTATIONS

Mutations involving nucleotides

Point mutation

Silent

Misesnse

Nonsense

Frame shift mutation – deletions and insertions

Trinucleotide repeat sequence

Mendelian disorders

Autosomal dominant diseases

Nervous

Huntington disease

Neurofibromatosis

Myotonic dystrophy

Tuberous sclerosis

Urinary

Polycystic kidney disease

Gastrointestinal

Familial polyposis coli

Hematopoietic

Hereditary spherocytosis

von Willebrand disease

Skeletal

Marfan syndrome

Ehlers-Danlos syndrome (some variants)

Osteogenesis imperfecta

Achondroplasia

Metabolic

Familial hypercholesterolemia

Acute intermittent porphyria

Autosomal Recessive Disorders

Metabolic

Cystic fibrosis

Phenylketonuria

Galactosemia

Homocystinuria

Lysosomal storage diseases

a1 -Antitrypsin deficienc

Wilson disease

Hemochromatosis

Glycogen storage diseases

Hematopoietic

Sickle cell anemia

Thalassemias

Endocrine

Congenital adrenal hyperplasia

Skeletal

Ehlers-Danlos syndrome (some variants)

Alkaptonuria

Nervous

Neurogenic muscular atrophies

Friedreich ataxia

Spinal muscular atrophy

X-Linked Recessive Disorders

Musculoskeletal

Duchenne muscular dystrophy

Blood

Hemophilia A and B

Chronic granulomatous disease

Glucose-6-phosphate dehydrogenase deficiency

Immune Agammaglobulinemia

Wiskott-Aldrich syndrome

Metabolic

Diabetes insipidus

Lesch-Nyhan syndrome

Nervous

Fragile-X syndrome

Biochemical and Molecular Basis of Some Mendelian Disorders

Enzyme Phenylalanine hydroxylase mutation: reduced amount of enzyme causing Phenylketonuria

Hexosaminidase mutation with stop codon:

reduced amount causing Tay-Sachs disease

Adenosine deaminase mutation causing Severe combined immunodeficiency

a1 –Antitrypsin mutations: impaired secretion from liver to serum, causing emphysema and liver cirrhosis

Low-density lipoprotein receptor mutations: Familial hypercholesterolemia

Vitamin D receptor mutations: Vitamin D-resistant rickets

Hemoglobin gene Deletions: reduced amount causing Thalassemia

Hb Point mutations: abnormal structure causing Sickle cell anemia

Cystic fibrosis transmembrane conductance regulator( CFTR) mutation causingCystic fibrosis

Collagen gene mutations cause reduced amount causing Osteogenesis imperfecta; Ehlers-Danlos syndromes, etc

Fibrillin mutation causing Marfan syndrome

Dystrophin Deletion with reduced synthesis:

Duchenne/Becker muscular dystrophy

Spectrin, ankyrin of RBC mutation: Hereditary spherocytosis

Factor VIII Deletions, insertion or nonsense mutations: reduced synthesis or abnormal factor VIII causing Hemophilia A

Rb protein Deletions causing Hereditary retinoblastoma

Neurofibromin gene mutation causing Neurofibromatosis type 1

Schematic diagram illustrating the pathogenesis of lysosomal storage diseases. In the example shown, a complex substrate is normally degraded by a series of lysosomal enzymes (A, B, and C) into soluble end products. If there is a deficiency or malfunction of one of the enzymes (e.g., B), catabolism is incomplete and insoluble intermediates accumulate in the lysosomes.

Some storage disesases

Lysosomal storage diseases

Gaucher’s disease

Niemann Pick Disease

Gangliosidosis

Sphingolipidosis

Tay Sachs disease

Sandhoff’s disease

Fabry’s disease

Glycogen storage diseases

Von Gierke’s disease

McArdle’s disease

Pompe’s disease

Pathways of glycogen metabolism. Asterisks mark the enzyme deficiencies associated with glycogen storage diseases