Genetics Lecture Flashcards by Cara stasz

inheritance of Huntington Disease

Autosomal Dominant

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inheritance of myotonic dystrophy

autosomal dominant

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Trinucleotide repeat, what concept leads to expansion in the next generation

Anticipation

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What trinucleotide expansion condition has higher risk if maternally inherited?

Mytonic dystrophy and fragile X

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What trinucleotide expansion condition has higher risk expansion if paternally inherited?

Huntington

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Myotonic Dystrophy

AD
CTG repeat
DMPK gene
3’ end
Less than 37 normal
40-90 mild >50s
90-1000 moderate, 20s-30s
>1000s congenital
affected 80-2000

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what is most common form of inherited intellectual deficiency

Fragile X

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Inheritance of Fragile X?

X linked dominant with reduced penetrance
(females can have it but a carrier MAY not have symptoms due to X inactivation)

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Fragile X

CGG repeats (ribosomal protein)
mild phenotype females
FMR1 gene
premutation carriers- 50/50 chance of transmission expanding allele
MALE PREMUTATION CARRIERS WILL PASS PREMUTATION TO AL DAUGHTERS BUT LESS LIKELY TO EXPAND
AGG repeats- stability!
FULL MUTATION is >200

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FXTAS

late onset progressive cerebellar ataxia, memory loss, cognitive decline, lower lim proximal muscle weakness.
PREMUTATION CARRIER FEMALES (age)

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how many repeats will lead to full mutation of fragile X

> 200

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how many repeats will lead to full mutation of huntington disease

> 40 CAG
more repeats, younger age of onset
neurodegenerative disease

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If a dad wants to know if a child is at risk but does not want to know if he has gene change what do you do?

Exclusion testing (linkage analysis- way to look at different alleles)

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how do you test for trinucleotide expansion repeats?

PCR OR SOUTHERN BLOT FOR SIZE OF REPEAT
if too big, methylation testing

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what do you test for methylation testing for fetus?

Amniotic fluid
CANNOT do methylation testing on placenta

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Ddx for increased NT (>99th %tile or >3mm)

aneuploidy
CHD
Skeletal Dysplasia
Genetic Syndromes (NOONAN, SLO)

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NT > 3.5 with normal genetic testing and anatomy, what is likihood of normal baby?

95%

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what is the most likely diagnosis with cystic hygroma

trisomy 21

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quad screen analytes

afp, hcg, inhibin, estriol

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what serum screening results with T21

“HI!”
HIGH HCG AND INHIBIN
LOW ESTRIOL AND AFP

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WHAT SERUM screening results for T18?

ALL LOW

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what is associated with extremely low estriol?

x linked ichythiosis
SLO

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what can cause a low fetal fraction?

obesity
aneuploidy
Mosaicism
drawn too early
maternal condition (autoimmune)
medication exposure (lovenox)

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what can cause false positive CFDNA results?

maternal malignancy
demise of co twin
maternal karyotype abnormality
placental mosaicism

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inheritance of spinal muscular atrophy?

autosomal recessive

what is a silent carrier for SMA?

2 normal copies of SMN on 1 allele then partner status must be determined

how do we screen for hemoglobinopathies?

all patients should have a CBC, Hb electrophoresis OR molecular genetic testing if concerned

most likely tested ashkenazi jewish conditions (ACOG)

CF, Tay Sachs, Canavans disease, familial dysautonomia

heteroplasmy vs variable expressivity

specific for mitochondrial conditions

risk of loss from CVS?

1 in 300

mosaics with wHAT chromosomes do you have to worry about uniparental disomy/trisomy rescue?

6,7,11,14,15 (lets say you do CVS and get mosaic trisomy 14. Follow up Amnio is normal. CONSIDER METHYLATION STUDIES TO RULE OUT UPD)

SIZE OF DEFECT TO SEE ON KARYOTYPE?

4-5 MB

WHAT IS CYTOGENETICS

STUDY OF STRUCTURE OF CHROM AND THEIR INHERITANCE- NEED LIVE RAPIDLY DIVIDING CELLS (AMINOCYTES!)

what is the most common mechanism for aneuploidy?

nondisjunction in meiosis I

benefit of karyotype over microarray?

both detect large aberrations Karyotype alone can see balanced translocations

what are some limitations of chromosomal microarray

cannot detect truly balanced translocations, does not detect all cases of mosaicism, no point mutations or intragenic mutations, risk of CNV uncertain significance

microarray result with abnormality (such as VUS) what is the next step?

test the parents

Spina bifida

bony defect with neural content/exposure. 99% have chiari II (banana sign, cerebellum protruding into foramen magnum) lemon sign- scalloping of frontal bones

Dddx of etiology of neural tube defect

mostly sporadic rare cases trisomy 13 or 18

what are clinical considerations of NTD?

Possibility of in utero vs postnatal repair- MOMS TRIAL route of delivery (Vaginal versus CD) Folic acid supplementation prognosis (worse if higher) 1-2% recurrence seizures, shunt, bladder/bowel dysfunction, walking TOP

MOMS TRIAL inclusion criteria

GA 19-25w6d Normal karyotype S1 lesion or higher confirmed chiari II on US and MRI

MOMS trial exclusion

obesity T2DM history of PTD uterine anomaly

Embryological development of anencephaly

failure of neuropore to close anteriorally

embryological development of spina bifida

failure of neuropore to close posteriorally

ddx for anencephaly

no calvarium with absence of neural tissue above orbits ddx: anencephaly, amniotic band syndrome, severe microcephaly, encephalocele, atelecephaly (small fluid-filled calviarum without intracranial structrures) LETHAL

risk factors for neural tube defect

folic acid deficiency, obesity, methotrexate, valproic acid, carbamezapine (folic acid antagonists)

nexty pregnancy management of NTD

supplement Folic acid 4 mg decreases recurrence by 70%

alobar holoprosencephaly genetics?

25-50% trisomy 13 SLO, Meckel Gruber, aicardi/fryns, velocardofacial syndrome

ALOBAR VERSUS LOBAR VERSUS SEMILOBAR

ALOBAR fused thalami with monoventricle LOBAR absent CSP, fused fornices, thalami separate SEMILOBAR - fused frontal lobes, thalami partially fused

what is a sacrococcygeal teratoma?

mass coming off sacrum, neoplasm derived from all 3 cell layers, mixed cystic/solid, color doppler for vascularity

what genetic syndromes have Cleft lip/palate

trisomy 13 trisomy 18 treacher collins 22q11.2 deletion

classic meckel gruber triad

renal cystic dysplasia encephalocele post axial polydactyly

HIGH YIELD AUTOSOMAL DOMINANT CONDITIONS

marfan, neurofibroomatosis, achondroplasia, ADPCKD, Ectrodactyly (split hand syndrome), tuberus sclerosis, 22q11.2 deletion

rule out x linked condition?

MALE TO MALE transmission

male passing to all females in pedigree Female passing to half of females half of males

could be X LINKED DOM

more males than females, skips... clue for

x linked recessive

imprinting pattern

males can pass on allele but they wont show the disease, but if female has the allele and passes it will be affected

different severity of condition where all have the same condition

variable expressivity

what is an x linked dominant condition, lethal in males- skin/hair/teeth related

incontinentia pigmenti

Genetics Lecture Flashcards

(60 cards)