genetics Flashcards
list X linked dominant dz
fragile X, Rett syndrome, hypophosphatemic ricketts, charcot marie tooth syndrome
List X linked recessive dz
glucose-6-phosphate dehydrogenase deficiency, duchenne muscular dystrophy, Lesch-Nyhan syndrome, hemophilia A and B
environmental factors in xeroderma pigmentosum
degree of exposure to UV light
allelic heterogeneity
nonsense vs missense mutation in factor VIII gene and Beta thalassemia- different mutations in same locus produce same phenotype
locus heterogeneity
mutations at different loci produce similar phenotype- ie. albinism
disease with incomplete penetrance
retinoblastoma and BRCA1 mutations- not everybody with mutated genotype will show phenotype
disease with variable expression
hemochromatosis and neurofibromatosis type 1- varying degrees of severity
dz with pleiotropy
marfan syndrome, cystic fibrosis, PKU- one gene contributes to multiple phenotypic effects
dz with locus heterogeneity
osteogenesis imperfecta
prader willi
loss of paternal allele from 15q at an imprinted locus, or inheriting both 15q from mom (25% uniparental disomy). Hyperphagia and obesity, neonatal hypotonia, hypogonadism
Angelman syndrome
loss of maternal allele from 15q at an imprinted locus, or inheriting both 15q from dad (5% uniparental disomy). Seizures, ataxia, happy disposition, inappropriate laughter
What kind of translocation is philadelphia chromosome
reciprocal
Cri Du Chat
microdeletion in p arm of chrom 5
hypophosphatemic rickets inheritance pattern and presentation
X-linked dominant disorder resutling in increased phosphate wasting at proximal tubule and results in rickets like presentation. Not responsive to vit D
Mitochondrial myopathies inheritance and presentation
mitochondrial mutation- ragged red fibers on muscle biopsy, myopathy, lactic acidosis and CNS diseases. Secondary to failure in oxidative phosphorylation
Achondroplasia
Autosomal dominant. Missense mutation in fibroblast growth factor receptor 3 (FGFR3) on chromosome
4 leads to inhibition of cartilage synthesis at
epiphysial growth plate. Dwarfism: long bones are short and thick, cranial and vertebral bones are spared. Autosomal dominant. Missense mutation in fibroblast growth factor receptor 3 (FGFR3) on chromosome
4 leads to inhibition of cartilage synthesis at
epiphysial growth plate. Dwarfism: long bones are short and thick, cranial and vertebral bones are spared. Autosomal dominant. Missense mutation in fibroblast growth factor receptor 3 (FGFR3) on chromosome
4 leads to inhibition of cartilage synthesis at
epiphysial growth plate. Dwarfism: long bones are short and thick, cranial and vertebral bones are spared. Autosomal dominant. Missense mutation in fibroblast growth factor receptor 3 (FGFR3) on chromosome
4 leads to inhibition of cartilage synthesis at
epiphysial growth plate. Dwarfism: long bones are short and thick, cranial and vertebral bones are spared.
Polycystic kidney disease
Autosomal dominant. Mutation of the PKD-1 gene on chromosome 16 (16 letters in PCK). Enlarged kidneys with tubular cysts bilaterally. Renal insufficiency, hematuria, HTN in middle age. Extra renal- liver cysts, berry aneurisms, mitral valve prolapse, colonic diverticulaAutosomal dominant. Mutation of the PKD-1 gene on chromosome 16 (16 letters in PCK). Enlarged kidneys with tubular cysts bilaterally. Renal insufficiency, hematuria, HTN in middle age. Extra renal- liver cysts, berry aneurisms, mitral valve prolapse, colonic diverticulaAutosomal dominant. Mutation of the PKD-1 gene on chromosome 16 (16 letters in PCK). Enlarged kidneys with tubular cysts bilaterally. Renal insufficiency, hematuria, HTN in middle age. Extra renal- liver cysts, berry aneurisms, mitral valve prolapse, colonic diverticula
Cystic fibrosis
AR. Mutation of CFTR chloride channel on chrom 7. Most common mutation is delta508. Abnormal protein folding. Diagnosis: sweat test. Treatment: N-acetylcysteine (cleaves mucus glycoproteins), infections
List the X linked recessive conditions
Be Wise, Fools GOLD Heeds Silly Hope: Bruton agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry disease, G6PD deficiency, Ocular albinism, Lesch-Nyhan, Duchenne MD, Hunter syndrome, Hemophilia A and B, Ornithine transcarbamylase deficiency.
Duchennes muscular dystrophy
X-linked recessive. Frameshift mutation of dystrophin gene- ineffective protein. Onset by 5 yrs. Calf pseudohypertrophy, proximal muscle weakness, Gowers maneuver, dilated cardiac myopathy, pulmonary infections, elevated CPK. Muscle biopsy shows necrosis, degeneration and regeneratio of fibers, fatty infiltration, decreased dystrophiin. Diagnosis by PCR
Becker muscular dystrophy
X lined recessive. Point mutation in dystrophin gene. Less severe than Duchenne.
Familial adenomatous polyposis
Autosomal dominant. Mutation of APC gene on chrom 5 (5 letters in polyp). Thousands of colonic polyps after puberty, adenocarcinoma by age 40. Increased risk for adenocarcinoma of duodenum, ampulla of vater
glycogen storage diseases
Autosomal recessive
Familial hypercholesterolemia
aka type II hyperlipidemia. Autosomal dominant. Mutation of LDL receptor on chrom 19. Elevated serum LDL, tendon xanthomas (lipid laden macrophages in skin), xanthelasmas around eyes, premature atherosclerosis, early MI
PKU
autosomal recessive
Sickle cell anemia
autosomal recessive
Fabrys disease
X linked recessive
hereditary hemorrhagic telangiectasia
Autosomal dominant. Telangiectasias of skin/mucus membranes of lips, tongue, fingertips. Recurrent epistaxis, arterio-venous malformation.
Hereditary spherocytosis
autosomal dominant. Defect in ankryin and spectrin (components of RBC cell membranes). RBCs contract to sphere shape and are removed by macrophages in spleen. Splenomegaly, hemolytic anemia, jaundice, pigmented gallstones. Treatment is splenectomy
Huntingtons disease
AD. Expansion of CAG trinucleotide repeat on chrom 4 (huntingtin protein). Degeneration of GABAergic neurons in caudate nucleus removes inhibitory input on extrapyramidal circuit- chorea. Manifests btw 20-40yrs. Personality changes, dementia
Lesch Nyhan syndrome
X linked recessive
Fragile X syndrome
X linked dominant. Trinucleotide repeat mutation in FMR-1 gene. CGG repeats. Autism/ADHD, elongated face with large jaw, large everted ears, maroorchidism (eXtra large testes, jaw, ears). Mitral valve prolapse. Diagnosed with PCR
Friedreichs ataxia
Autosomal recessive. GAA sequence expansion on chrom 9. Mitochondrial iron builds up causing free radical damage, degeneration of nerve tissue in spinal cord, gait ataxia (hammer toes), dysarthria, hand clumsiness, loss of sense of position, impaired vibratory sensation, areflexia in all limbs
Marfan syndrome
, hypermobile jointsAD. Mutation of fibrillin gene on chrom 15. pleotropy. Tall, thin body, pectus excavatum. Bilateral subluxation of lenses, cystic degeneration of media of elastic arteries resulting in dissecting aneurysms. Aortic and mitral valve insufficiency
MEN I
AD. Mutation of MEN I tumor suppressor gene. Hyperplasia and tumors of Parathyroid, Pituitary (prolactinomas), pancreas (insulinoma, zollinger ellison)
MEN IIA
AD. Mutation of RET proto-oncogene. Hyperplasia and tumors of parathyroid, pheochromocytoma, meduallary carcinoma of thyroid.
MEN IIB (III)
AD. Mutation of RET proto-oncogene. Pheochromocytoma, medullary carcinoma of thyroid, muco-cutaneous neuromas, marfanoid habitus
Myotonic dystrophy
Autosomal dominant. CTG repeat expansion. Muscle loss, myotonia, cardiac conduction defects, testicular atrophy, frontal baldness, cataracts
Neurofibromatosis type I
AD. Mutation of tumor suppressor gene NF-1 on
chromosome 17. Neurofibromas, café-au-lait spots, Lisch nodules, risk for meningiomas and pheochromocytomas.AD. Mutation of tumor suppressor gene NF-1 on
chromosome 17. Neurofibromas, café-au-lait spots, Lisch nodules, risk for meningiomas and pheochromocytomas.
Neurofibromatosis type II
AD. Mutation of tumor suppressor gene NF-2 on
chromosome 22. bilateral acoustic neuromas (schwannomas), neurofibromas, café-au-lait spots, risk for meningiomas and ependymomasAD. Mutation of tumor suppressor gene NF-2 on
chromosome 22. bilateral acoustic neuromas (schwannomas), neurofibromas, café-au-lait spots, risk for meningiomas and ependymomas
Causes of Down syndrome
95% are meiotic nondisjunctions of homologous chromosomes, 4% are robertsonian translocation, 1% are mosaicism from mitotic nondisjunction
Tuberous sclerosis
AD. Incomplete penetrance. Multiple cortical, retinal, and pulmonary hamartomas. Ash leaf spots, renal cysts, renal angiomyolipomas, cortical tubers, increased astrocytomas, seizures, mental retardation
von Hippel-Lindau disease
AD. Mutaiton of tumor suppressor gene VHL on chrom 3 (VHL is 3 words). Normal gene product tags proteins with ubiquitin for degradation. Elevated HIV leads to activation of angiogenic growth factors. Hemangioblastomas. Von Hippel tumor in retina. Lindau tumors in cerebellum, brainstem, spinal cord. cysts of liver, pancreas, kidneys. bilateral renal cell carcinomas
Down syndrome pre natal screening
decreased alpha-fetoprotein, increased B-HCG, decreased unconjugated estriol, increased inhibin A
Edwards syndrome
trisomy 18. Mental retardation, low set ears, micrognathia, overlapping flexed fingers, rocker bottom feet, congenital heart defects, renal malformations. Death within first year
edwards syndrome pre natal screening
Decreased alpha-fetoprotein, decreased beta-hCG, decreased estriol, normal inhibin A
Patau syndrome
Trisomy 13. Mental retardation, cleft lip/palate, cardiac defects, renal abnormalities, microcephaly/holoprosencephaly, polydactyly. Death within first year
Pataue syndrome pre-natal screening
normal alpha fetoprotein, beta-HCG, estriol and inhibin A
Cri Du Chat
Deletion of short arm of chrom 5. High pitch cat like cry. Mental retardation. Congenital heart disease (VSD), microcephaly
Williams syndrome
Microdeletion of long arm of chrom 7 including elastin gene. Mental retardation, elfin face, hypercalcemia (increased sensitivity to Vit D), cheerful demeanor and ease with strangers, developmental delay but strong language skills. Cardiovascular problems
DiGeorge syndrome
Microdeletion at 22q11. CATCH-22: cardiac defects, abnormal facies, thymic aplasia, cleft palate, hypocalcemia/hypoparathyroidism, 22 chrom.
List the trinucleotide repeat expansion diseases
Huntingtons, myotonic dystrophy, Friedreich ataxia, Fragile X
albinism
AR, mutation in tyrosinase, pale color urine.
PKU
AR, mutation in phenylalanine hydroxylase, musty odor of urine
Tay Sachs
AR, mutation in hexosaminidase A, Cherry red spot in macula
G6PD deficiency
XR, mutation in G6PD resulting in Heinz bodies.
Hemophilia A
XR, mutation in Factor VIII, increased coag time
Hemophilia B
XR, mutation in Factor IX, increased coag time
Lesch Nyhan syndrome
XR, mutation in HGPRT, severe hyperuricemia
