Genetic disorders Flashcards
Burkitt lympoma characterized by what genetic mutation
t(8:14) MC; translocation of c-myc gene from cr 8 to Ig heavy chain locus on cr 14 poma 62, FA400
child presents with extranodal mass of neoplastic intermediate-sized B-cells on jaw what oncogene is being overexpressed
c-myc oncogene which was translocated to cr 14 promotes cell growth poma62, FA400
dysgenesis of seminiferous tubules (hyalinized) and abnormal leydig cell function causes what hormonal change what genetic defect is this
increased FSH due to decreased inhibin decreased testosterone, increased LH, and hence increased estrogen Klinefelter syndrome, 47 XXY FA 578
47 XXY what physical features
Klinefelter syndrome gynecomastia, female hair distribution, testicular atrophy, long extremities FA 578
pt has short stature, streak ovary (ovarian dysgenesis), and webbed neck what is genetic sex karyotype
XO Turner syndrome FA 578
pt presents with post-pubertal macroorchidism (enlarged testes), autism, long face with large jaw, mitral valve prolapse what gene is affected
trinucleotide repeat disorder (CGG)n X-linked defect affecting methylation and expression of FMR1 gene Fragile X-syndrome FA 85, RRP 135
lower segment of body greater than upper segment eunuchoid body shape
klinefelter syndrome 47 XXY FA 578
child presents with hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia what is the gene deletion
paternal chromosome 15 PW gene is lost (uniparental disomy of maternal cr 15 or just a microdeletion) Prader-Willi syndrome FA 81, RRP 146
why is patient with prader-willi syndrome obese
insatiable appetite by increased levels of ghrelin produced by stomach and arcuate nucleus in hypothalamus RRP 146
clinical findings of paternal chromosome 15 deletion
hyperphagia, hypotonia, intellectual disability, genital hypoplasia FA 81, RRP 146
clinical findings maternal chromosome 15 deletion (udp15 or microdeletion)
mental retardation, jerky wide-based gait with hand flapping, outbursts of inappropriate laughter (happy puppet syndrome) Angelman syndrome FA 81, RRP 146
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
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
treatment for chronic myelogenous leukemia
RRP 328, FA 402
Imatinib mesylate - oral tyrosine kinase inhibitor RRP 328, FA 402
neurofibromatosis 1 is a neurocutaneous disorder associated with what findings
FA 491
cafe au lait-colored macules Lische nodules, which is pigmented hamartoma of the iris
FA 491
Skin tumors of neurofibromatosis 1 are derived from
FA 491
neural crest cells
FA 491
neurofibromatosis 2 (central) is associated with
RRP 697
cafe au lait spots
bilateral acoustic neuromas (schannomas) which results in sensorineural hearing loss, tinnitus
what heart defect is associated with 46 XO
FA 578
preductal coartaction
this results in a strong brachial pulse and weak femoral pulse
Turner’s syndrome
Trinucleotide repeat of CGG
FA 85
Fragile X syndrome
Trinucleotide repeat of CAG
FA 85
Huntington’s disease
also shows genetic anticipiation
possible karyotypes of a partial mole
FA 580
69 XXX; 69 XXY; 69XYY
these are from 2 sperm + 1 egg
hyatidiform mole with no fetal parts
what are the possible karyotypes
FA 580
46XX; 46XY
complete mole
infant with cleft lip/palate, microcephaly
holoprosencephaly, polydactyly, cutis aplasia
what is genetic defect
FA 626
trisomy 13
patau syndrome
infant with microcephaly, rocker-bottom feet, clenched hands, and structural heart defect
FA 626
trisomy 18
edwards syndrome
Genetic anticipation is characterized by what?
What is an example?
FA 80
Increased severity or earlier onset of disease in succeeding generations.
E.g. Trinucleotide repeat diseases, e.g. Huntington dz
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
Autosomal dominant CAG repeat expansion.
Huntington disease. Shows genetic anticipation.
Cr 4 (87)
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?
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)
Child pt presents with cafe-au-lait spots, cutaneous neurofibromas, pigmented iris hamartomas.
What is the inheritance pattern of this dz?
What chromosome?
Autosomal dominant, 100% penetrance with variable expression. (FA 83)
Chromosome 17.
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?
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)
What is the gene product of NF-2?
Merlin (schwannomin) protein, is a tumor supressor gene. FA 236
