DISEASES BY INHERITANCE PATTERNS

Question 1

Autosomal recessive

Answer 1

Phenylketonuria
Cystic fibrosis
Sickle cell anemia
Xeroderma pigmentosum
Tay-sachs disease

Question 2

Autosomal dominant

Answer 2

Achondroplasia
Brachydactyly
Familial hypercholesterolemia
Marfan syndrome
Porphyria

Question 3

X-linked Recessive

Answer 3

Red-green colorblindness
Hemophilia A
Lesch-Nyhan Syndrome
Muscular dystrophy
Fragile X syndrome

Question 4

X-linked Dominant

Answer 4

X-linked hypophosphatemia
Alport Syndrome

Question 5

● ION TRANSPORT disorder

● Affects fluid secretion in exocrine glands and epithelial lining

● Abnormally viscous secretions - obstruct organ passages

Answer 5

CYSTIC FIBROSIS

Question 6

Chronic lung disease - recurrent infection
Pancreatic insufficiency
Steatorrhea
Malnutrition
Cirrhosis
Intestinal obstruction
Male infertility

Answer 6

CYSTIC FIBROSIS

Question 7

Most common lethal genetic disease affecting Caucasian populations

1 in 2500 live births

Answer 7

Cystic fibrosis

Question 8

Autosomal Recessive

(+) heterozygote carriers - higher incidence of respiratory and pancreatic diseases

Answer 8

Cystic fibrosis

Question 9

CYSTIC FIBROSIS

Abnormal Epithelial Cl -Channel protein - ________ gene mutation

Answer 9

CFTR (7q31.2) gene mutation

Question 10

Defective Cl - ion exchange system Altered salt, water and Cl- transport

Answer 10

Cystic fibrosis

Question 11

CFTR (7q31.2) gene mutation

Answer 11

Cystic fibrosis

Question 12

▪ 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

Answer 12

CYSTIC FIBROSIS

Question 13

Cystic fibrosis

Affected protein?

Loss of CFTR leads to defects in_____?

Answer 13

cystic fibrosis transmembrane conductance regulator (CFTR)

chloride transport

Question 14

Familial hypercholesterolemia

Affected protein?

Loss of LDL receptor leads to_____

Answer 14

LDL receptor

hypercholesterolemia

Question 15

Tay-Sachs disease

Protein affected?

Lack of the lysosomal enzyme leads to storage of______ in neurons

Answer 15

Hexosaminidase B- subunit

GM2 gangliosides

Question 16

PHENYLKETONURIA

● Inborn Error of_____

● Autosomal____

● Deficiency of_____ Enzyme

● gene muration?

Answer 16

Metabolism

Recessive

Phenylalanine Hydroxylase (PAH)

PAH Gene (12q24) Mutation

Question 17

● Severe mental retardation - 6 months

● Seizures

● Decreased hair/skin pigmentation

● Eczema

● Musty/Mousy urine odor

Answer 17

Phenylketonuria

Question 18

PHENYLKETONURIA

● Inability to convert Phenylalanine to____

Answer 18

Tyrosine

Question 19

Increased levels

excreted in urine and sweat

Circulated in the brain neurologic problems

Answer 19

Pku

Question 20

Decreased Tyrosine levels decreased skin/hair pigmentation (Melanin precursor)

Answer 20

Phenylketonuria

Question 21

● Autosomal Recessive Hemoglobinopathy

● Point mutations in Beta-Globin polymerization deoxygenated hemoglobin

Answer 21

SICKLE-CELL ANEMIA

Question 22

○ ○ ○ ○

Red cell distortion
Hemolytic anemia
Microvascular
Obstruction
Ischemic tissue damage

Answer 22

SICKLE-CELL ANEMIA

Question 23

• 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

Answer 23

Sickle Cell Anemia

Question 24

• 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

Answer 24

Sickle Cell Anemia

Question 25

● Familial Cancer syndrome w/ Cutaneous Manifestations ● Autosomal Recessive

Answer 25

XERODERMA PIGMENTOSUM

Question 26

XERODERMA PIGMENTOSUM

Answer 26

XPA (9q22) Gene Mutation

Question 27

Impaired nucleotide excision repair ○ (+) melanoma / non-melanoma (BCC) skin cancers

Answer 27

XERODERMA PIGMENTOSUM

Question 28

Mucus production that blocks ducts of certain glands and lung passages

Answer 28

Cf

Question 29

Excess accumulation of phenylala- nine in blood, mental retardation

Answer 29

Pku

Question 30

Abnormal hemoglobin, blood vessel blockage

Answer 30

Sca

Question 31

Lack of DNA repair enzymes, sensitivity to light, skin cancer

Answer 31

Xp

Question 32

Improper metabolism in nerve cells, death in childhood

Answer 32

Tsd

Question 33

● Most common form of skeletal dysplasia ● Major cause of Dwarfism

Answer 33

ACHONDROPLASIA

Question 34

ACHONDROPLASIA ● Autosomal____ ● Retarded cartilage growth ● _______ mutations in Fibroblast Growth Factor Receptor 3 (FGFR3)

Answer 34

Dominant Gain-of-function

Question 35

Brachydactyly

Answer 35

HOXD13 gene

Question 36

HOXD13 gene

Answer 36

Brachydactyly

Question 37

• 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.

Answer 37

Hoxd13 Brachydactyly

Question 38

FAMILIAL HYPERCHOLESTEROLEMIA ● “_____Protein Disease” ● Autosomal____ ● defective LDL receptor - loss of feedback control & elevated cholesterol levels

Answer 38

Receptor Dominant

Question 39

● “Receptor Protein Disease” ● Autosomal Dominant ● defective LDL receptor - loss of feedback control & elevated cholesterol levels

Answer 39

FAMILIAL HYPERCHOLESTEROLEMIA

Question 40

FAMILIAL HYPERCHOLESTEROLEMIA

Answer 40

LDLR gene mutation (80-85%)

Question 41

● 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)

Answer 41

MARFAN SYNDROME

Question 42

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)

Answer 42

Connective Dominant Fibrillin-1

Question 43

Gene mutation in Marfan syndrome

Answer 43

● FBN1 (15q21.1) gene missense mutation Fibrillin-1 Glycoprotein defect (misfolding)

Question 44

Skeletal abnormalities, ocular changes, and cardiovascular lesions Lax ligaments, spinal deformities (kyphosis/scoliosis) Ectopia Lentis MVP, Aortic Dissection

Answer 44

MARFAN SYNDROME

Question 45

● Disorders of PORPHYRIN metabolism ● Autosomal Dominant

Answer 45

PORPHYRIA

Question 46

PORPHYRIA ● Disorders of_____ metabolism ● Autosomal____ ● Porphyrin: pigments present in hemoglobin, myoglobin, and cytochromes Essential for producing Heme

Answer 46

PORPHYRIN Dominant

Question 47

Dwarfism associated with abnormalities in growth

Answer 47

Achondroplasia

Question 48

Malformed hands with shortened fingers

Answer 48

Brachydactyly

Question 49

Elevated cholesterol levels, cardio- vascular disease

Answer 49

Familial hypercholesterolemia

Question 50

Connective tissue disorder, possible aortic aneurysm

Answer 50

Marfan syndrome

Question 51

Inability to metabolize porphyrin, episodes of mental disturbance, such as hallucinations or paranoia

Answer 51

Porphyria

Question 52

● 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

Answer 52

HEMOPHILIA A

Question 53

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

Answer 53

Deletions

Question 54

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

Answer 54

DUCHENNE MUSCULAR DYSTROPHY

Question 55

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

Answer 55

DUCHENNE MUSCULAR DYSTROPHY

Question 56

● “Fatty Infiltration” of muscle fibers ● Muscle weakness, pseudohypertrophy, joint contractures, cardiomyopathy

Answer 56

DUCHENNE MUSCULAR DYSTROPHY

Question 57

● Trinucleotide repeat disorder ● X-linked Recessive ● Second most common cause of Mental Retardation

Answer 57

FRAGILE-X SYNDROME

Question 58

FRAGILE-X SYNDROME ● Trinucleotide repeat disorder ●_____ ● Second most common cause of\__ Retardation

Answer 58

X-linked Recessive Mental

Question 59

FGXM grne

Answer 59

FMR1 Gene (Xq27.3) trinucleotide mutation “Fragile” site Loss of FMRP function

Question 60

● Neurodegenerative effects - MR ● Abnormal Facial Features Long face w/ large mandible Large everted ears ● Macro-orchidism (90%)

Answer 60

FRAGILE-X SYNDROME

Question 61

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

Answer 61

Xq27.3

Question 62

○ Regulates intracellular transport of polysomes to dendrites Regulates translation

Answer 62

Familial Mental Retardation Protein (FMRP)

Question 63

Lack of HGPRT protein, mental retardation, self-mutilation

Answer 63

Lesch-Nyhan syndrome

Question 64

Duchenne-type, progressive condition with muscle wasting

Answer 64

Muscular dystrophy