path 5

  1. Point mutation/deletion in 15q12 chromosome on maternal allele with paternal imprinting
    Angelman Syndrome
  2. Uniparental disomy of paternal chromosome 15 which was imprinted (silenced)
    Angelman syndrome
  3. UBE3A affected in Angelmans syndrome is a
    ubiquitin ligase
  4. "happy puppet", inappropriate laughter, seizures, ataxic gait, mentally retarded
    Angelmans syndrome
  5. Silencing of maternal or paternal allele
    genomic imprinting(maternal/paternal)
  6. imprinting occurs before or after fertilization?
    before fertilization
  7. differential patterns of dna methylation at CG nucleotides, hisotone H4 deacetylayion and methylation is
  8. 15q12 gene imprinted(silenced) on maternal chromosome, and deletion of paternal 15q12
    prader willi syndrome
  9. uniparental disomy of maternal chromosome 15q12 which has been imprinted(silenced)
    prader-willi syndrome
  10. genes in 15q11.2-q13(imprinted on maternal and expressed on paternal chromosome) encodes
    small nuclear riboprotein N
  11. protein that controls gene splicing and expressed highly in brain and heart
    small nuclear riboprotein N
  12. prader willi syndrome is caused by a loss of the protein function of
    small nuclear riboprotein N
  13. mental retardation, short stature, hypotonia, profound hyperphagia, obesity, small hands and feet, hypogonadism, decreased fetal and neonatal activity, mild intrauterine growth retardation, facial dysmorphism, behavioral disturbances - self injurious behavior, skin picking most common
    Prader-Willi syndrome
  14. height< 152 cm(< 3rd%tile)
    weight>95 kg(>97th%)
    BMI 41
    Head Circumference 52 cm(3-10%)
    normal bifrontal diamter, almond shaped eyes, thin upper lip, downturned corners of mouth and small mandible, truncal obesity with abdominal striae, hand and feet small (16 cma nd 20 cm < 3rd %tile) with tapering fingers, multiple lesions from scratching present on arms legs and face
    prader willi syndrome
  15. Long repeating sequence of three nucleotides guanine(G) and cytosine(C)
    Fragile X syndrome
  16. second most common genetic cause of mental retardation, 1 in 1550 for affected males, 1 in 1 in 8000 for affected females
    fragile x syndrome
  17. x-linked, mutation within familial mental retardation-1 (FMR-1) gene
    fragile x syndrome
  18. constriction in long arm of x chromosome when cells cultured in folate deficient medium, appears chromosome is broken referred to as a fragile site
    fragile x syndrome
  19. carrier males aka normal transmitting males (carry fragile x mutation but are clinically and cytogenetically normal) 20 % transmit trait through all daughters (phenotypically normal) to affected grandchildren, what percent of carrier females are affected i.e. mentally retarded)
  20. risk of phenotypic effect depends on position of individual in pedigree, clinical features of fragile x syndrome worsen with each succesive generation , this is called
  21. 6 - 55 CGG repeats on FMR-1 is
  22. in premutations of fragile x syndrome how many CGG repeats are on FMR-1 gene (in normal transmitting males and carrier females) ?
    55-200 CGG repeats
  23. Full mutations of FMR-1 (in affected individuals seen) is how many CGG repeats?
    200-4000 CGG repeats
  24. Dramatic amplification of CGG repeats occurs when premutation is transmited by (premutation -> amplification of CGG repeats -> full mutations)
    A carrier female
  25. 50 % of females with full fragile x syndrome mutation are clinically affected because of
    unfavorable lyonization(x inactivation) so more cells where chromosome with mutation is active
  26. premature ovarian failure (females)
    fragile x syndrome
  27. intention tremors, cerebellar ataxia, MAY PROGRESS TO PARKINSONISM, STARTS IN 6TH DECADE in MALES
    fragile x syndrome (premutation abnormalities milder and occur later in life)
  28. fragile x syndrome occurs when the dna of the 5' region of the fmr1 gene due to > 200 repeats of CGG becomes
    abnormally methylated ( then extends upstream to promoter region of gene, transcriptional suppression of FMR1 occurs and absence of FMRP familial mental retardation protein results in a Loss of Function of it)
  29. affects males, mentally retarded (iq from 20-60 range), long face with large mandible, large everted ears, large testicles MACRO-ORCHIDISM) in 90% of post pubertal males, hyperextensible joints high arched plate mitral valve prolaps in some pt's so mimics conecctive tissue disorder
    Fragile X syndrome
  30. method of choice for fragile x diagnosis is
  31. in fragile x syndrome to make distinction between pre mutations and mutations both prenatally as well as post natally for which the information is used for genetic counseling we use
    Southern blot analysis
  32. most common sex chromosome abnormality in females, 1 in 2000 live born females, complete or partial monosomy of x chromosome, hypogonadism in phenotypic females
    turner syndrome
  33. 45 x karyotype 57 %, structural abnormalities ( e.g.partial monosomy of x chromosome ) 14% such as isochrome of q arm -> loss of p arm, deletion of parts of both arms -> ring chromosome, deletetion of parts of either arm, mosaics is 29 %
    turner syndrome
  34. fetal ovaries develop normally early in embryogenesis but then accelerated loss of oocytes by 2 years
    turner syndrome
  35. haploinsufficiency of SHOX -> short stature
    Turner Syndrome
  36. presents in infancy: edema of dorsum of hand and foot (b/c lymph stasis), swelling of nape of neck b/c distended lymphatic channels, cystic hygroma (bilateral neck webbing, congenital heart disease 25-50% of pt's, left sided cardiovascular abnormalities such as preductal coarctation of aorta which is seen most frequently and bicuspid aortic valve which are the most important causes of increased mortality in
    turner syndrome
  37. at puberty failure to develop normal secondary sex characteristics, infantile genitalia, inadequate breast development, sparse pubic hair
    turner syndrome
  38. normal mental status, impaired nonverbal visual spatial information processing, short stature, primary amenorrhea
    turners syndrome
  39. 50% of pt's autoantibodies that react with thyroid gland, half of these develop clinically manifested hypothyriodism via glucose intolerance obesity, insulin resistance (therapy with Growth Hormone used commonly in these patients worsens insulin resistance)
    turners syndrome
Card Set
path 5
path 5