Genetic disorders

Question 1

Burkitt lympoma characterized by what genetic mutation

Answer 1

t(8:14) MC; translocation of c-myc gene from cr 8 to Ig heavy chain locus on cr 14 poma 62, FA400

Question 2

child presents with extranodal mass of neoplastic intermediate-sized B-cells on jaw what oncogene is being overexpressed

Answer 2

c-myc oncogene which was translocated to cr 14 promotes cell growth poma62, FA400

Question 3

dysgenesis of seminiferous tubules (hyalinized) and abnormal leydig cell function causes what hormonal change what genetic defect is this

Answer 3

increased FSH due to decreased inhibin decreased testosterone, increased LH, and hence increased estrogen Klinefelter syndrome, 47 XXY FA 578

Question 4

47 XXY what physical features

Answer 4

Klinefelter syndrome gynecomastia, female hair distribution, testicular atrophy, long extremities FA 578

Question 5

pt has short stature, streak ovary (ovarian dysgenesis), and webbed neck what is genetic sex karyotype

Answer 5

XO Turner syndrome FA 578

Question 6

pt presents with post-pubertal macroorchidism (enlarged testes), autism, long face with large jaw, mitral valve prolapse what gene is affected

Answer 6

trinucleotide repeat disorder (CGG)n X-linked defect affecting methylation and expression of FMR1 gene Fragile X-syndrome FA 85, RRP 135

Question 7

lower segment of body greater than upper segment eunuchoid body shape

Answer 7

klinefelter syndrome 47 XXY FA 578

Question 8

child presents with hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia what is the gene deletion

Answer 8

paternal chromosome 15 PW gene is lost (uniparental disomy of maternal cr 15 or just a microdeletion) Prader-Willi syndrome FA 81, RRP 146

Question 9

why is patient with prader-willi syndrome obese

Answer 9

insatiable appetite by increased levels of ghrelin produced by stomach and arcuate nucleus in hypothalamus RRP 146

Question 10

clinical findings of paternal chromosome 15 deletion

Answer 10

hyperphagia, hypotonia, intellectual disability, genital hypoplasia FA 81, RRP 146

Question 11

clinical findings maternal chromosome 15 deletion (udp15 or microdeletion)

Answer 11

mental retardation, jerky wide-based gait with hand flapping, outbursts of inappropriate laughter (happy puppet syndrome) Angelman syndrome FA 81, RRP 146

Question 12

blood work shows increased proliferation of myeloid-derived cells, including neutrophils, basophils, metamyelocytes; low leukocyte alkaline phosphatase due to low activity of mature granulocytes what is the gene translocation dz?

FA 402, RRP 327

Answer 12

t(9;22)BCR-ABL ABL proto-oncogene translocates to BCR and they fuse creating a new tyrosine kinase chronic myelogenous leukemia FA 402, RRP 327

Question 13

treatment for chronic myelogenous leukemia

RRP 328, FA 402

Answer 13

Imatinib mesylate - oral tyrosine kinase inhibitor RRP 328, FA 402

Question 14

neurofibromatosis 1 is a neurocutaneous disorder associated with what findings

FA 491

Answer 14

cafe au lait-colored macules Lische nodules, which is pigmented hamartoma of the iris

FA 491

Question 15

Skin tumors of neurofibromatosis 1 are derived from

FA 491

Answer 15

neural crest cells

FA 491

Question 16

neurofibromatosis 2 (central) is associated with

RRP 697

Answer 16

cafe au lait spots

bilateral acoustic neuromas (schannomas) which results in sensorineural hearing loss, tinnitus

Question 17

what heart defect is associated with 46 XO

FA 578

Answer 17

preductal coartaction

this results in a strong brachial pulse and weak femoral pulse

Turner’s syndrome

Question 18

Trinucleotide repeat of CGG

FA 85

Answer 18

Fragile X syndrome

Question 19

Trinucleotide repeat of CAG

FA 85

Answer 19

Huntington’s disease

also shows genetic anticipiation

Question 20

possible karyotypes of a partial mole

FA 580

Answer 20

69 XXX; 69 XXY; 69XYY

these are from 2 sperm + 1 egg

Question 21

hyatidiform mole with no fetal parts

what are the possible karyotypes

FA 580

Answer 21

46XX; 46XY

complete mole

Question 22

infant with cleft lip/palate, microcephaly

holoprosencephaly, polydactyly, cutis aplasia

what is genetic defect

FA 626

Answer 22

trisomy 13

patau syndrome

Question 23

infant with microcephaly, rocker-bottom feet, clenched hands, and structural heart defect

FA 626

Answer 23

trisomy 18

edwards syndrome

Question 24

Genetic anticipation is characterized by what?
What is an example?

FA 80

Answer 24

Increased severity or earlier onset of disease in succeeding generations.

E.g. Trinucleotide repeat diseases, e.g. Huntington dz

Question 25

Pt presents with chorea, dementia, and is found to have caudate degeneration.

What is the inheritance pattern of this disease?

What chromosome?

FA 624, 80, 87

Answer 25

Autosomal dominant CAG repeat expansion.

Huntington disease. Shows genetic anticipation.

Cr 4 (87)

Question 26

Pt presents with chorea and dementia.

Pt’s father had same symptoms and had a slightly later onset of disease.

What is the etiology of this disease?

Answer 26

Degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia.

AD disorder Cr 4 characterized by expanded trinucleotide repeats (CAG) in the hungintin gene. (poma 188)

Question 27

Child pt presents with cafe-au-lait spots, cutaneous neurofibromas, pigmented iris hamartomas.

What is the inheritance pattern of this dz?

What chromosome?

Answer 27

Autosomal dominant, 100% penetrance with variable expression. (FA 83)

Chromosome 17.

Question 28

Child presents with Lische nodules, cafe-au-lait spots, and is found to have increased metanephrines in the urine.

What is the mechanism of this gene?

Answer 28

Classic presentation of Neurofibromatosis-1, typically seen associated with pheochromocytoma (FA 624)

NF-1 is a tumor supression gene; activates Ras GTPase activating protein (neurofibromin)(FA 236)

Question 29

What is the gene product of NF-2?

Answer 29

Merlin (schwannomin) protein, is a tumor supressor gene. FA 236