DISEASES BY INHERITANCE PATTERNS Flashcards
Autosomal recessive
Phenylketonuria
Cystic fibrosis
Sickle cell anemia
Xeroderma pigmentosum
Tay-sachs disease
Autosomal dominant
Achondroplasia
Brachydactyly
Familial hypercholesterolemia
Marfan syndrome
Porphyria
X-linked Recessive
Red-green colorblindness
Hemophilia A
Lesch-Nyhan Syndrome
Muscular dystrophy
Fragile X syndrome
X-linked Dominant
X-linked hypophosphatemia
Alport Syndrome
● ION TRANSPORT disorder
● Affects fluid secretion in exocrine glands and epithelial lining
● Abnormally viscous secretions - obstruct organ passages
CYSTIC FIBROSIS
Chronic lung disease - recurrent infection
Pancreatic insufficiency
Steatorrhea
Malnutrition
Cirrhosis
Intestinal obstruction
Male infertility
CYSTIC FIBROSIS
Most common lethal genetic disease affecting Caucasian populations
1 in 2500 live births
Cystic fibrosis
Autosomal Recessive
(+) heterozygote carriers - higher incidence of respiratory and pancreatic diseases
Cystic fibrosis
CYSTIC FIBROSIS
Abnormal Epithelial Cl -Channel protein - ________ gene mutation
CFTR (7q31.2) gene mutation
Defective Cl - ion exchange system Altered salt, water and Cl- transport
Cystic fibrosis
CFTR (7q31.2) gene mutation
Cystic fibrosis
▪ People with ____ can have a variety of symptoms, including:
• Very salty-tasting skin
• Persistent coughing, at times with phlegm
• Frequent lung infections including pneumonia or bronchitis
• Poor growth or weight gain in spite of a good appetite
• Frequent greasy, bulky stools or difficulty with bowel movements
• Male infertility
• Wheezing or shortness of breath
CYSTIC FIBROSIS
Cystic fibrosis
Affected protein?
Loss of CFTR leads to defects in_____?
cystic fibrosis transmembrane conductance regulator (CFTR)
chloride transport
Familial hypercholesterolemia
Affected protein?
Loss of LDL receptor leads to_____
LDL receptor
hypercholesterolemia
Tay-Sachs disease
Protein affected?
Lack of the lysosomal enzyme leads to storage of______ in neurons
Hexosaminidase B- subunit
GM2 gangliosides
PHENYLKETONURIA
● Inborn Error of_____
● Autosomal____
● Deficiency of_____ Enzyme
● gene muration?
Metabolism
Recessive
Phenylalanine Hydroxylase (PAH)
PAH Gene (12q24) Mutation
● Severe mental retardation - 6 months
● Seizures
● Decreased hair/skin pigmentation
● Eczema
● Musty/Mousy urine odor
Phenylketonuria
PHENYLKETONURIA
● Inability to convert Phenylalanine to____
Tyrosine
Increased levels
excreted in urine and sweat
Circulated in the brain neurologic problems
Pku
Decreased Tyrosine levels decreased skin/hair pigmentation (Melanin precursor)
Phenylketonuria
● Autosomal Recessive Hemoglobinopathy
● Point mutations in Beta-Globin polymerization deoxygenated hemoglobin
SICKLE-CELL ANEMIA
○ ○ ○ ○
Red cell distortion
Hemolytic anemia
Microvascular
Obstruction
Ischemic tissue damage
SICKLE-CELL ANEMIA
• Autosomal recessive disorder resulting from a mutation in B-globin that causes deoxygenated hemoglobin to self-associate into long polymers that distort (sickle) the red cell
Sickle Cell Anemia
• Episodic lockage of vessels by sickle red cells causes pain crises and tissue infarction, particularly of the marrow and spleen
• Red cell membrane damage caused by repeated bouts of sickling results in a moderate to severe hemolytic anemia
Sickle Cell Anemia
● Familial Cancer syndrome w/ Cutaneous Manifestations
● Autosomal Recessive
XERODERMA PIGMENTOSUM
XERODERMA PIGMENTOSUM
XPA (9q22) Gene Mutation
Impaired nucleotide excision repair
○
(+) melanoma / non-melanoma (BCC) skin cancers
XERODERMA PIGMENTOSUM
Mucus production that blocks
ducts of certain glands and lung passages
Cf
Excess accumulation of phenylala-
nine in blood, mental retardation
Pku
Abnormal hemoglobin, blood
vessel blockage
Sca
Lack of DNA repair enzymes,
sensitivity to light, skin cancer
Xp
Improper metabolism in nerve cells,
death in childhood
Tsd
● Most common form of skeletal dysplasia
● Major cause of Dwarfism
ACHONDROPLASIA
ACHONDROPLASIA
● Autosomal____
● Retarded cartilage growth
● _______ mutations in Fibroblast Growth Factor Receptor 3 (FGFR3)
Dominant
Gain-of-function
Brachydactyly
HOXD13 gene
HOXD13 gene
Brachydactyly
• Transcription factors: Homeobox genes, such as HOD /3, are frequently mutated in brachydactyly syndromes.
• Signal transduction molecules: FGFR3 mutations are responsible for achondroplasia and thanatophoric dysplasia, both of which manifest as dwarfism.
Hoxd13 Brachydactyly
FAMILIAL HYPERCHOLESTEROLEMIA
● “_____Protein Disease”
● Autosomal____
● defective LDL receptor - loss of feedback control & elevated cholesterol levels
Receptor
Dominant
● “Receptor Protein Disease”
● Autosomal Dominant
● defective LDL receptor - loss of feedback control & elevated cholesterol levels
FAMILIAL HYPERCHOLESTEROLEMIA
FAMILIAL HYPERCHOLESTEROLEMIA
LDLR gene mutation (80-85%)
● Connective tissue disorder
● Autosomal Dominant
● Loss of Fibrillin-1 causes the s/s through 2 mechanisms:
Loss of structural support (loss of microfibrils) and, Excessive TGF- signaling activation (high metalloprotease activity)
MARFAN SYNDROME
MARFAN SYNDROME
●_____ tissue disorder
● Autosomal_____
● Loss of_____ causes the s/s through 2 mechanisms:
Loss of structural support (loss of microfibrils) and,
Excessive TGF- signaling activation (high metalloprotease activity)
Connective
Dominant
Fibrillin-1
Gene mutation in Marfan syndrome
● FBN1 (15q21.1) gene missense mutation Fibrillin-1 Glycoprotein defect (misfolding)
Skeletal abnormalities, ocular changes, and cardiovascular lesions
Lax ligaments, spinal deformities (kyphosis/scoliosis)
Ectopia Lentis MVP,
Aortic Dissection
MARFAN SYNDROME
● Disorders of PORPHYRIN metabolism
● Autosomal Dominant
PORPHYRIA
PORPHYRIA
● Disorders of_____ metabolism
● Autosomal____
● Porphyrin:
pigments present in hemoglobin, myoglobin, and cytochromes Essential for producing Heme
PORPHYRIN
Dominant
Dwarfism associated with abnormalities in growth
Achondroplasia
Malformed hands with shortened fingers
Brachydactyly
Elevated cholesterol levels, cardio-
vascular disease
Familial hypercholesterolemia
Connective tissue disorder, possible
aortic aneurysm
Marfan syndrome
Inability to metabolize porphyrin, episodes of mental disturbance, such as hallucinations or paranoia
Porphyria
● Most common hereditary disease associated with LIFE-THREATENING BLEEDING
● Deletions, nonsense mutations in Factor VIII
- (-) Factor VIII synthesis
● X-Linked Recessive
Males and Homozygous Females affected
● Easy bruising
● Massive hemorrhage
● Hemarthroses
HEMOPHILIA A
HEMOPHILIA A
● Most common hereditary disease associated with LIFE-THREATENING BLEEDING
●_______, nonsense mutations in Factor VIII
- (-) Factor VIII synthesis
● X-Linked Recessive
Males and Homozygous Females affected
● Easy bruising
● Massive hemorrhage
● Hemarthroses
Deletions
Inherited disorder of skeletal muscle
X-Linked Recessive
DMD gene deletion/frameshift mutation - (-) Dystrophin
Dystrophin:
Key component of Dystrophin Glycoprotein Complex (DGC)
Links the cytoskeleton and the BM outside the cell - provides myofiber stability
DUCHENNE MUSCULAR DYSTROPHY
Inherited disorder of skeletal muscle
X-Linked Recessive
DMD gene deletion/frameshift mutation - (-) Dystrophin
Dystrophin:
Key component of Dystrophin Glycoprotein Complex (DGC)
Links the cytoskeleton and the BM outside the cell - provides myofiber stability
DUCHENNE MUSCULAR DYSTROPHY
●
“Fatty Infiltration” of muscle fibers
●
Muscle weakness, pseudohypertrophy, joint contractures,
cardiomyopathy
DUCHENNE MUSCULAR DYSTROPHY
● Trinucleotide repeat disorder
● X-linked Recessive
● Second most common cause of Mental Retardation
FRAGILE-X SYNDROME
FRAGILE-X SYNDROME
● Trinucleotide repeat disorder
●_____
● Second most common cause of\__ Retardation
X-linked Recessive
Mental
FGXM grne
FMR1 Gene (Xq27.3) trinucleotide mutation
“Fragile” site Loss of FMRP function
● Neurodegenerative effects - MR
● Abnormal Facial Features
Long face w/ large mandible
Large everted ears
● Macro-orchidism (90%)
FRAGILE-X SYNDROME
FRAGILE-X SYNDROME
● FMR1 gene
Located on______ Multiple tandem
Repeats of CGG Normal: 6-55 (ave. 29) repeats
Premutation: 55-200
Full Mutation: 250-4000 or greater
● Amplified CGG repeats
Carrier female > Carrier male
Xq27.3
○
Regulates intracellular transport of polysomes to dendrites
Regulates translation
Familial Mental Retardation Protein (FMRP)
Lack of HGPRT protein, mental
retardation, self-mutilation
Lesch-Nyhan syndrome
Duchenne-type, progressive condition with muscle wasting
Muscular dystrophy
