path 5

Point mutation/deletion in 15q12 chromosome on maternal allele with paternal imprinting

Uniparental disomy of paternal chromosome 15 which was imprinted (silenced)

UBE3A affected in Angelmans syndrome is a

"happy puppet", inappropriate laughter, seizures, ataxic gait, mentally retarded

Silencing of maternal or paternal allele

imprinting occurs before or after fertilization?

differential patterns of dna methylation at CG nucleotides, hisotone H4 deacetylayion and methylation is

15q12 gene imprinted(silenced) on maternal chromosome, and deletion of paternal 15q12

uniparental disomy of maternal chromosome 15q12 which has been imprinted(silenced)

genes in 15q11.2-q13(imprinted on maternal and expressed on paternal chromosome) encodes

protein that controls gene splicing and expressed highly in brain and heart

prader willi syndrome is caused by a loss of the protein function of

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

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

Long repeating sequence of three nucleotides guanine(G) and cytosine(C)

second most common genetic cause of mental retardation, 1 in 1550 for affected males, 1 in 1 in 8000 for affected females

x-linked, mutation within familial mental retardation-1 (FMR-1) gene

constriction in long arm of x chromosome when cells cultured in folate deficient medium, appears chromosome is broken referred to as a fragile site

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)

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

6 - 55 CGG repeats on FMR-1 is

in premutations of fragile x syndrome how many CGG repeats are on FMR-1 gene (in normal transmitting males and carrier females) ?

Full mutations of FMR-1 (in affected individuals seen) is how many CGG repeats?

Dramatic amplification of CGG repeats occurs when premutation is transmited by (premutation -> amplification of CGG repeats -> full mutations)

50 % of females with full fragile x syndrome mutation are clinically affected because of

premature ovarian failure (females)

intention tremors, cerebellar ataxia, MAY PROGRESS TO PARKINSONISM, STARTS IN 6TH DECADE in MALES

fragile x syndrome occurs when the dna of the 5' region of the fmr1 gene due to > 200 repeats of CGG becomes

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

method of choice for fragile x diagnosis is

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

most common sex chromosome abnormality in females, 1 in 2000 live born females, complete or partial monosomy of x chromosome, hypogonadism in phenotypic females

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 %

fetal ovaries develop normally early in embryogenesis but then accelerated loss of oocytes by 2 years

haploinsufficiency of SHOX -> short stature

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

at puberty failure to develop normal secondary sex characteristics, infantile genitalia, inadequate breast development, sparse pubic hair

normal mental status, impaired nonverbal visual spatial information processing, short stature, primary amenorrhea

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)