Genetic Diseases

Question 1

Down Syndrome

Answer 1

Trisomy 21, i21+21, Robertsonian translocation, mosaic DS, partial trisomy 21. Typically a maternal nondisjunction event, frequency increases with age. Cognitive impairment, GI defects, facies, hypotonia, transverse palmar crease, cardiac issues . Risk of early AD, autism, ALL, and AML.

Question 2

Edward’s Syndrome

Answer 2

Trisomy 18. Growth impairment, hypertonicity, clentched hand, narrow hips, siezures, intellectual disabilities. Congenital Heart Disease.

Question 3

Patau Syndrome

Answer 3

Trisomy 13. Forebrain doesn?t sseparate into hemispheres, facial cleft, polydactyly, congenital heart disease.

Question 4

Klinefelter Syndrome

Answer 4

47, XXY. Tall stature, hypogonadism, Underdeveloped secondary sexual characters, slight breast devel. Usually infertile. Can be a mosaic.

Question 5

XYY Syndrome

Answer 5

47 XYY. Indistinguishable physically and mentally from males and fertile. Inc risk of behavioral and educational problems in speech and lang. NOT associated with criminals.

Question 6

Turner Syndrome

Answer 6

45, XO. Short stature, webbed neck, edema, shield chest, wide nipples, renal and cardiovascular anomalies (bicuspid aortic valve), failure in ovarian development. Sterile. Can be mosaic.

Question 7

Charcot-Marie-Tooth Disease

Answer 7

dup 17p11.2. Duplication of the peripheral myelin protein PMP-22 gene from NAHR causing 3 alleles to be expresssed. Weakness of foot and lower leg muscles, eventually muscle atrophy of hands. Hammer toes.

Question 8

Hereditary Neuropathy with liability to pressure palsies

Answer 8

del 17p11.2 (AD) Deletion of the gene encoding PMP-22 from NAHR. Integral glycoprotein in nerve cells. When loss of pro function, pain and tingling in extremities like “arm has fallen asleep” but severe and long symptoms

Question 9

Velocardiofacial Syndrome

Answer 9

del 22q11. Cleft palate, septal defects

Question 10

DiGeorge’s Syndrome

Answer 10

del 22q11. Outflow tract defects in heart, facies

Question 11

Prader-Willi Syndrome

Answer 11

del 15q11-q13 of paternally derived chromosome or imprinting issues. SNORD116 a snoRNA genes which may be involved in mRNA modification. Hypotonic, trouble eating in infancy then excessive eating, short stature, sleep apnea from obesity, hypogonadism, opthalmic problems and intellectual disability. Growth hormone can improve stature and reduce apetite.

Question 12

Angelman Syndrome

Answer 12

del 15q11-q13 of maternally derived chromosome or imprinting issues. Repressed gene UBE3A, a ubiquitin ligase. Short stature, severe intellectual disabilities,autism, seizures.

Question 13

Acute Promyelocytic Leukemia

Answer 13

t(15;17)(q24;q21). PML/RARA fusion. High bone marrow blasts. Characterized by Auer rods. Treated with retinoic acid (vitamin a

Question 14

Acute Myelogenous Leukemia

Answer 14

t(8;21)(q22;q22). ETO/AML fusion.

Question 15

Chronic Myeloid Leukemia

Answer 15

t(9;22)(q34;q11.2). BCR/ABL1 fusion. Night sweats, fatigue, lobulated cells, splenomegaly. Treated with Gleevec.

Question 16

IDIC 15

Answer 16

Supernumerary marker chromosome 47, i15q (inverted duplicted isodicentric) or a simple maternally inherited interstitial duplication of causes autism, hypotonia, seizures.

Question 17

Early onset Alzheimer’s Disease

Answer 17

Locus heterogeneity related disease resulting in amyloid-B build up. Early onset the result of a mutation in PS-1, PS-2, or APP genes result in the same phenotype.

Question 18

Androgen Insensitivity

Answer 18

Mutated X linked gene for androgen receptor. XY females that don’t develop uterus.

Question 19

Adrenal Hyperplasia

Answer 19

46 XX female is exposed to testosterone and has abnormal cortisol production resulting in ambiguous genetalia

Question 20

Smith-Lemli-Opitz syndrome

Answer 20

AR, Abnormal cholesterol synthesis (a precursor to testosterone) resulting in ambiguous male genitalia

Question 21

Kallman syndrome

Answer 21

X linked AR, the hypothalamus doesn’t stimulate the pituitary to produce LH and FSH which normally stimulate testosterone production.

Question 22

Hypospadias

Answer 22

Other than Smith-Lemli-Opitz and Kallman syndromes, a del 4p16.3 results in non funtional Steriod 5a-reductase, a necessary protein in testosterone metabolism

Question 23

Duchanne Muscular Dystrophy

Answer 23

DMD Xp21.2 Large deletions, nonsense or frameshift mutations cause premature termination of protein. Abnormal gait, calf pseudohypertrophy, progressive deterioration of myocardium and respiratory muscles. Gower’s manuver.

Question 24

Becker Muscular Dystrophy

Answer 24

Similar to but more mild than DMD and occurs at same locus, but the result of an inframe deletion which leaves protein semi funcitonal

Question 25

Osteogenesis Imperfecta Type 1

Answer 25

AD. Premature termination of COL1A1 the gene for procollagen 1. Collagen composed of 2x procollagen 1 and 1x procollagen 2. Mutant gene results in slow collagen production thus reduced amount in tissue. Brittle bones, increased fractures, blue schlera.

Question 26

Osteogenesis Imperfecta Type 2, 3, 4

Answer 26

Mutated COL1A2 (frameshift) resulting in abnormal procollagen 2 production. 1/2 of collagen made normal but 1/2 have the mut protein. More severe phenotype than the loss of function in OIT type 1. Often lethal.

Question 27

Hemoglobin Kempsey

Answer 27

Asp99Asn missense mutation resulting in a higher oxygen binding affinity. At distal tissue sites, unable to unload much oxygen which causes body to up reg RBC production causing polycythemia

Question 28

Fragile X

Answer 28

CGG repeats in 5’UTR of FMR1 cuase methylation and supression of transcription. Characteristic facies, hypotonia, cognitive deficits, and autism.

Question 29

Huntington Disease

Answer 29

CAG repeats in the Huntington Disease gene (HD gene) results in a long chain of glutamine residues rendering the protein non functional. Norm 40. Severe neurodegenerative disorder with an onset correlated to # of repeats. Genetic anticipation; paternal expansion only.

Question 30

Myotonic Dystrophy

Answer 30

CTG repeats in DMPK gene resulting in weakness, myotonia, cognitive defects. Less than 35 repeats is normal but repeats can get into the thousands with increasing phenotypic severity and earlier onset. Maternal expansion.

Question 31

Phenylkentonuria

Answer 31

Defects in Phenylalanine hydroxylase (PAH) or cofactor BH4. Results in high phe level in blood and urine, epilepsy, cog defects and microcephaly. High alelic heterogeneity with varied phenotype severity. Treat with low phe diet W/ BH4 mut, patient also needs medicine for nuerotransmitter balance.

Question 32

1a-antitrypsin deficiency

Answer 32

(ATD) Mutation in SERPINA1 a protease inhibitor that is suicide inhibitor of serine protease elastase. Elastin necessary for tissue but too much is bad. Increased risk of developing emphysema, liver cirrhosis, liver cancer. Symptoms more severe in smoker or high pollution. Z/Z is 15% act, improperfolding cuases accumulation and liver damage. S/S is 50% active, unstable protein but normal. S/Z mild.

Question 33

Tay-Sach’s Disease

Answer 33

Lysosomal Storage Disorder where HexA is defective. HEXA (ch15) and HEXB (ch5) make HexA (a and b subs + activator) and HexB (2x b sub) enzymes that breakdown GM2 gangliosides. Also may be caused by GM2AP activator needed for GM2gang degredation.