Pregnancy and Early Childhood 🗸

Question 1

silent mutation

Answer 1

mutated codon codes for the same amino acid

Question 2

triplet expansion

Answer 2

a triplet is repeated

Question 3

recessive autosomal inheritance is more common in which types of families

Answer 3

consanguineous (same ancestor)

Question 4

de-novo dominant inheritance

Answer 4

occurs when a de-novo variant in one copy of a gene is sufficient to result in a clinical phenotype

Question 5

de-novo

Answer 5

from neither parent, a new mutation

Question 6

Array-CGH

Answer 6

allows you to look for sub-microscopic deletions or duplications of chromosomal material across the whole genome
only detects chromosome imbalance

Question 7

next generation sequencing (NGS)

Answer 7

finds small sequence changes

Question 8

Non-invasive prenatal testing (NIPT)

Answer 8

uses free foetal DNA in maternal circulation
currently used for sex determination and trisomy testing
if there is more of chromosome 21, the pregnancy is high risk (99%) of trisomy 21, if not then it is low risk

Question 9

advantages of NIPT

Answer 9

allows for fewer tests
non-invasive so no risk of miscarriage

Question 10

disadvantages of NIPT

Answer 10

can give false negatives due to inadequate foetal fraction, only 10% of the DNA comes from the foetus
can give false positives due to confined placental mosaicism or maternal malignancies

Question 11

Invasive testing

Answer 11

uses aCGH
sample taken from placenta (chorionic villus sampling) or from amniotic fluid (amniocentesis)

Question 12

what can invasive testing indicate?

Answer 12

when scanning you can see foetal abnormalities like small size, symmetrical growth failure, increased nuchal thickness or structural failures (brain/heart etc)
you can also see if the parent has a balanced chromosomal rearrangement

Question 13

advantages of invasive testing

Answer 13

higher resolution
technically easier
rapid

Question 14

disadvantages of invasive testing

Answer 14

also finds polymorphisms (SNPs or CNVs) so may make incidental findings
1/100 risk of miscarriage for invasive tests

Question 15

termination of pregnancy (TOP)

Answer 15

surgical TOP before 13 weeks, must be induced after that
no time limit on TOP if there is a serious abnormality or health concern of the mother

Question 16

when would NGS be used on an infants genome?

Answer 16

when the infant presents with a phenotype indicative of a genetic disorder, after other testing has taken place, conformation of sorts

Question 17

filtering mutations

Answer 17

3 million variants = exclude variants know to be polymorphisms
1000s of variants = keep variants known to affect gene function
100s of variants = does the gene explain the phenotype?
should leave one mutation, which is causative

Question 18

trio exome sequencing

Answer 18

NGS used to sequence the exome of the mum, dad and kid
used as a first line test for unwell children with a likely monogenic disorder
20-40% diagnostic rate with no environmental cause and up to 70% for a kid with abnormal neurological presentation

Question 19

pre-implantation testing

Answer 19

perform a genetic test on an embryo before re-implanting one with the ‘correct’ genotype
can be considered in parental chromosome abnormality or single gene conditions

Question 20

genetic testing in kids

Answer 20

identify phenotype, dysmorphology database and other resources can help
use aCGH to look for chromosomal imbalance
use UGS to look for smaller mutation, requires filtering