Cytogenetics Ii

Front 1

Using fetal blood sampling to confirm a mosaic trisomy placenta would not be useful for which chromosome?

Back 1

20

Front 2

What is the most common Robertsonian translocation associated with Down syndrome?

Back 2

14;21

Front 3

Major features of trisomy 13

Back 3

holoprosencephaly, apnea, seizures, deafness, microphthalmia, microcephaly, cleft palate, coloboma, low set ears, hypotelorism, polydacttyly, club foot, flexion deformity of fingers

Front 4

Most common Robertsonin translocation seen, and incidence

Back 4

13;14
1/1,100

Front 5

Risk for serious congenital abnormality in de novo reciprocal translocation

Back 5

6.1%

Front 6

Risk for serious congenital abnormality in de novo Robertsonian translocation

Back 6

3.7%

Front 7

Risk for serious congenital abnormality in de novo inversions

Back 7

9.4%

Front 8

Name 4 things that could cause a clinical anomaly in a person with a de novo BALANCED rearrangement

Back 8

submicroscopic deletions and duplications, interruption of a critical gene, position effect (like X-autosome translocation), UPD

Front 9

What is the most common type of structural rearrangement seen in humans? Frequency?

Back 9

Robertsonian
1/1000

Front 10

Carriers of Robertsonian translocation sare at increased risk for what 3 things?

Back 10

infertility, unbalanced offspring, offspring with UPD

Front 11

When does the ACMG recommend testing for UPD when a Robertsonian translocation is identified?

Back 11

Any Robertsonin involving chromosome 14 or 15

Front 12

Percent of human genes which are imprinted

Back 12

less than 5%

Front 13

Neurologic abnormalities of Angelman syndrome

Back 13

Hypotonia of trunk, hypertonia of extremities
stiff-legged walking
broad gait with arms flexed
poor balance and ataxia
seizure disorder with EEG abnormalities
severe MR

Front 14

Clinical findings of Prader-Willi

Back 14

hypotonia
hypogonadism
hyperphagia and obesity
dysmorphic features
short stature
DD/MR
behavioral problems

Front 15

Male gonadal features of Prader-Willi

Back 15

cryptorchidism
scrotal hypoplasia
small penis

Front 16

Puberty in males with Prader-Willi

Back 16

no voice change
no male body habitus
no facial or body hair
infertility

Front 17

Puberty in females with Prader-Willi

Back 17

normal breast development
no or sparse periods
infertility

Front 18

Desccribe the IQ strengths and weaknesses in Prader-Willi

Back 18

strengths--reading, visual-spatial, word search, jigsaws, long-term memory
weaknesses-math, sequential processing, short-term memory

Front 19

What % of adults with Prader-Willi have true pschosis?

Back 19

5-10%

Front 20

Imprinting center mutations cause what % of Angelman? Prader-Willi?

Back 20

3-5% of Angelman
1-3% of Prader-Willi

Front 21

Recurrence risk of Angelman if mom has a UBE3A mutation

Back 21

1%-50%--depends on whether sporadic or not

Front 22

If you do methylation studies on an Angelman patient, what types of mutations WILL and WON'T be picked up?

Back 22

Yes: maternal deletion will show different pattern, paternal UPD will show different pattern, imprinting center mut will show different pattern. NO-maternal UBE3A gene mutation--will look normal

Front 23

possible ways to get Angelman, and percentage of each

Back 23

maternal deletion=70-75%
paternal UPD=3-5%
maternal imprinting center mutation=7-9%
maternal UBE3A mutation=10%

Front 24

Describe the process of diagnostic testig for Angelman or PW

Back 24

1. chromosome analyis (pick up translocation or deletion)
2. methylation study (picks up deletion/UPD.imprinting center mut)
3. If negative, sequence UBE3A in Angelman, obesity gene SIM1 in PW
If positive, do FISH for deletion, UPD studies, IC defect studies

Front 25

If PW is suspected and methylation and chromosomes appear normal, what other locus/gene could be investigated?

Back 25

obesity gene SIM1 at 6q16.2

Front 26

Features of Russell-Silver

Back 26

head-preserving growth delay, pre and post-natal.
Trianglar face, prominent forehead, micrognathia, downturned mouth, blue sclera.
cafe au-lait spots
leg lenght discrepancy,. 2-3 syndactyly, clinodactyly
hypospaidas
usually normal intelligence

Front 27

Chroomosome 11 genes assoiated with Russell-Silver

Back 27

IGF2 (normally paternally expressed)
H19 (normally maternally expressed)

Front 28

abdominal defects associated with Beckwith-Weideman

Back 28

omphalocele
visceromegaly
embryonal tumor
adrenocortical cytomegaly
rena. abnormalities

Front 29

Describe monitoring for neoplasms in Beckwith-Wiedeman.

Back 29

Blood AFP every 6 weekks until 4 years old--for hepatoblastoma.
Abdominal u/s every 3-4 months tuntil 7-8-for Wilms.

Front 30

In the Beckwith-Wiedemann region, which genes are NORMALLY maternally expressed? paternally espressed?

Back 30

maternal =H19, CDKN1C
paternal =IGF2

Front 31

Features of Albright's Hereditary Osteodystrophy

Back 31

AD
short, obesity
MR
Brachydactyly
cataract, nystagmus
hypocalcemia
ectopic ossification
basal ganglia and choroid plexus calcification
seizures

Front 32

Name some disorders associated with imprinting problems of GNAS

Back 32

Albright hereditary osteodystrophy
Pseudohypoparathyroidism (PHP)
Pseudopseudohypoparathyroidism (PPHP)
Progressive Osseous Heteroplasia (POH)

Front 33

Features of paternal UPD 14

Back 33

polyhydramnios
DD/MR
short stature
small thorax=resp. distress
short broad neck
omphalocele/diastasis recti
depressed nasal bridge
hirsute forehead
protruding philtrum
small palpebral fissures'blepharophimosis
camptodactyly

Front 34

Features of maternal UPD 14

Back 34

IUGR
short stature
precocious puberty
hypotonia
scoliosis
truncal obesity
motor delay
may have normal cognitive
nasal speech
recurrent ear infections
hydrocephalus

Front 35

Features of Wolf-Hirschornh

Back 35

hypertelorism
pronounced glabella
simple ear
cleft lip/palate
growh retardation
heart defects
hypospadias/cryptorchidism
MR/seizures

Front 36

Percent of cri du chat that is de novo

Back 36

85%

Front 37

De novo cri du chat comes from which parent's chromosome 80% of the time?

Back 37

paternal

Front 38

Features of Williams syndrome

Back 38

periorbital fullness
medial eyebrow flare
long philtrum
heart defect (supravalvular aortic stenosis)
short stature
progressive dysplasia of joints
narrowed renal arteries
MR
riendly personality
hyperacusis (sensitive to loud noises)

Front 39

Features of Miller-Dieker

Back 39

lissencephaly
MR, seizures
prominent forehead with vertical grooves
small nose and mandible
protuberant upper lip

Front 40

Features of Smith-Magenis

Back 40

Flat midface, thick lips, arched eyebrows, pronounced philtrum, renal defects, myopia/strabismus/retinal dysplasia, hearing loss, heart defects, behavior issues

Front 41

A BAC array consists of peobes of what length? What is the smallest deletion detectable?

Back 41

~171 kb
~85 kb

Front 42

An oligo array consists of probes of what size?

Back 42

about 60 bp

Front 43

Best cells to use for chromosome analyssis

Back 43

white blood cells, T lymphocytes

Front 44

Clinical indications for chromosome analysis

Back 44

Growth and dev problems
Stillbirth
Infertility
Family history
Neoplasia
AMA

Front 45

Recurrence risk for Prader-Willi

Back 45

The risk to sibs is less than 1% if the affected child has a deletion or uniparental disomy, up to 50% if the affected child has a mutation of the imprinting control center, and up to 25% if a parental chromosomal translocation is present.

Front 46

Location and cause of NF1

Back 46

del 17q11.2

Front 47

Location and cause of Phelan-McDermid

Back 47

del 22q13.3

Front 48

Most common microdeletion syndrome, and frequency

Back 48

DiGeorge
1/2000-4000

Front 49

Percent of 22q del patients with heart defect

Back 49

74%

Front 50

What % of 22q deletions are de novo?

Back 50

94%