Genetics

Question 1

variable expressivity

Answer 1

phenotype varies among individuals with the same genotype (different disease severity)

Question 2

incomplete penetrance

Answer 2

not all individuals with a mutant gene show mutant phenotype

Question 3

pleiotropy

Answer 3

one gene contributes to multiple phenotypic effects

Question 4

mosaicism

Answer 4

presence of genetically distinct cell lines in the same individual, arises from mitotic errors after fertilization

Question 5

heteroplasmy

Answer 5

presence of both normal and mutated mtDNA, resulting in variable expression of mitochondrial inherited disease

Question 6

uniparental disomy

Answer 6

offspring gets 2 copies of a chromosome from 1 parent (heterodisomy is a meiosis 1 error, isodisomy is a meiosis II error)

Question 7

imprinting

Answer 7

epigenetic process involving methylation - gene is silenced without a change in sequence

Question 8

Prader-Willi syndrome

Answer 8

maternal imprinting: gene from mom is normally silent and Paternal gene is deleted/mutated

• • leads to hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia
• • Prader Willi is Paternal

Question 9

Angelman syndrome

Answer 9

paternal imprinting: gene from dad is usually silent and Maternal gene is mutated/deleted

• • inappropriate laughter, seizures, ataxia, and severe intellectual disability
• angelMan has Maternal mutation

Question 10

Autosomal Dominant Polycystic Kidney Disease

Answer 10

• adult onset, autosomal dominant
• bilateral, massively enlarged kidneys due to large cysts
• 85% due to PKD1 mutation on Chromosome 16

Question 11

FAP

Answer 11

• autosomal dominant
• APC gene mutation leading to multiple colonic polyps that will progress to cancer if colon is not removed
• on chromosome 5

Question 12

hereditary hemorrhagic telangiectasia

Answer 12

• AD inherited disorder of blood vessels
• telangiectasias, recurrent epistaxis, skin discolorations, AVMs, GI bleeding, hematuria
• aka Osler-Weber-Rendu

Question 13

Hungtington disease

Answer 13

• AD disease with CAG repeat on chromosome 4

- depression, progressive dementia, choreiform movements, caudate atrophy, decreased GABA and Ach

Question 14

NF1

Answer 14

• AD disorder with 100% penetrance, variable expression

- mutation in NF1 gene on chromosome 17 leads to cafe-au-lait spots and cutaneous neurofibromas

Question 15

NF2

Answer 15

• AD disorder with NF2 mutation on chromosome 22

- bilateral acoustic schwannomas, juvenile cataracts, meningiomas, and ependymomas

Question 16

von Hippel-Lindau disease

Answer 16

• AD disorder with numerous benign and malignant tumors

- deletion of VHL gene (tumor suppressor) on chromosome 3

Question 17

chromosome mutations of autosomal dominant disorders

Answer 17

3- VHL
4- huntington
5- FAP

16- ADPKD
17- NF1
22- NF2

Question 18

Duchenne muscular dystrophy

Answer 18

• x linked frameshift mutation in dystrophin gene
• onset before 5 years, dilated cardiomyopathy
• increased CPK and aldolase
• confirm diagnosis with western blot and muscle biopsy

Question 19

Becker muscular dystrophy

Answer 19

• point mutation in dystrophin gene

- adolescent onset, less severe than Duchenne

Question 20

myotonic type 1 muscular dystrophy

Answer 20

• CTG trinucleotide repeat expansion in DMPK gene –> abnormal expression of myotin protein kinase –> myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy and arrhythmia

Question 21

Fragile X

Answer 21

• x linked defect affecting methylation and expression of FMR1 gene (CGG repeat)
• post-pubertal macroorchidism, long face with large jaw, large everted ears, autism, mitral valve prolapse
• Fragile X = Xtra large testes, jaw and ears

Question 22

Autosomal trisomies

Answer 22

• Downs (21-Drinking age) - duodenal atresia, hirschsprung, ostium primum ASDs, increased bHCG
• Edwards (18-Election age) - low set Ears, prominent occiput, clenched hands, decreased bHCG
• Patau syndrome (13-Puberty) - microcephaly, cleft lip/palate, holoprosencephaly, polydactyly
• common to all - decreased PAPP-A, increased nuchal translucency, intellectual disability, congenital heart disease,

Question 23

Robertsonian translocation

Answer 23

nonreciprocal chromosomal translocation that occurs when long arms of 2 acrocentric chromosomes fuse at the centromere and the 2 short arms are lost

Question 24

Cru-du-chat syndrome

Answer 24

congenital microdeletion of 5p (short arm)

- microcephaly, mod-severe intellectual disability, high-pitched cry, epicanthal folds, VSD

Question 25

Williams syndrome

Answer 25

congenital microdeletion of long arm of chromosome 7 (7q), which includes elastin gene
- distinctive “elfin” facies, intellectual disability, hypercalcemia, well developed verbal skills and friendliness with strangers, CV probs

Question 26

22q11 deletion sydromes

Answer 26

CATCH-22

• Cleft palate, Abnormal facies, Thymic aplasia (T cell deficiency), Cardiac defects, Hypocalcemia 2/2 parathyroid aplasia
• Di George - thymic, parathyroid and cardiac defects
• Velocardiofacial syndrome - palate, facial and CV defects