Trigger 9: DDs examples

Question 1

schizophrenia has a lifetime prevalence of

Answer 1

1%

Question 2

schizophrenia is …..% heritable

Answer 2

80%

Question 3

thought to be caused by high burden of

Answer 3

de novo mutations

Question 4

autism spectrum disorder prevalence

Answer 4

1.5%

Question 5

autism is ….% heritable

Answer 5

50-90%

Question 6

autism spectrum disorder have a comple

Answer 6

genetic architecture

Question 7

ASD can be

Answer 7

monogenic and syndromic forms

- complex multifactorial causes

Question 8

ASD caused by

Answer 8

high burden of de novo mutations and large CNVs

Question 9

ASD is caused by an interplay between

Answer 9

familial background and high risk events (e.g. de novo mutation), explaining varying clinical manifestations

Question 10

prevalence of intellectual disability

Answer 10

1-2%

Question 11

heritability of intellectual disability

Answer 11

50-90%

Question 12

intellectual disability is defined as having and IQ below

Answer 12

70

Question 13

intellectual disability is

Answer 13

very heterogenous

Question 14

intellectual disability like ASD has

Answer 14

monogenic and syndromic forms

Question 15

intellectual disability can be caused by

Answer 15

environmental factors (e.g. mother drinking whilst pregnant)

Question 16

intellectual disability caused by a

Answer 16

ugh burden of de novo mutations and large CNVs

Question 17

many disorders are overlapping

Answer 17

conditions

e. g. ASD overlapping with SCZ
e. g. ASD overlapping with ID

Question 18

de novo heterozygous mutations are a common

Answer 18

cause of dominant DD

Question 19

inherited variants are a

Answer 19

common cause of recessive DD

Question 20

homozygous

Answer 20

two copies of the same variant, one from each parent

Question 21

compound heterozygous

Answer 21

The presence of two different mutant alleles at a particular gene locus, one on each chromosome of a pair.

Question 22

halpoinsufficnecy

Answer 22

only having a single functioning copy of a gene is not enough for normal function mutations caused by a dominant phenotype

Question 23

severe HI means that

Answer 23

genes are intolerant to loss of one functioning copy

Question 24

better explanation of HI

Answer 24

when the normal phenotype requires the protein product of both alleles and reduction of 50% (e.g. loss of function of one allele) of gene function results in an abnormal phontype

Question 25

a situation in which the total level of gene product (protein) produced by a cell is

Answer 25

about half of the normal level and not sufficient enough to permit normal cell functioning

Question 26

causes of HI

Answer 26

• inherited loss of function mutations in one allele

- de novo loss of function mutations in one allele

Question 27

although the wild-type allele still produces the standard amount products..

Answer 27

the total product is insufficient to produce standard phenotype

Question 28

NGLY1 is an

Answer 28

autosomal recessive disease which leads to N-glycanase 1 deficiency

Question 29

N-glycanase 1 deficiency

Answer 29

o Impaired ability to deglycosylate protein cells accumulate misfolded glycoproteins

Question 30

physical and neurological symptoms of NGLY1

Answer 30

o Lack of tears, developmental delay, movement disorder, elevated enzymes

Question 31

coffin-siris syndrome occurs due a mutation in

Answer 31

ARID1B

Question 32

what sort of mutation occurs in ARID1B to cause Coffin-Siris

Answer 32

de novo loss of function

Question 33

ARID1B is a

Answer 33

o Chromatin remodeller (changes DNA accessibility for gene expression)

Question 34

ARID1b is the

Answer 34

top diagnostic gene in DD-0.7%

Question 35

phenotype of Cofin-Siris (ARID1B)

Answer 35

♣ Developmental delay, speech delay, abnormalities in pinky finger or toes, short sighted, feeding difficulties
♣ Overlaps with other disorders

Question 36

treatment for coffin-siris

Answer 36

no treatment- genetic counselling

Question 37

16p11.2 microdeletion/ duplication

Answer 37

• Copy number variants (deletion or duplication)

- Usually new ‘de novo’ dominant mutation

Question 38

16p11.2 microdeletion/ duplication phenotypes

Answer 38

• intellectual disability, autism, developmental delay
  o duplication- risk of being underweight
  o deletion- risk of obesity

Question 39

16p11.2 microdeletion/ duplication within

Answer 39

7-8 MB of DNA (over 60 genes)

Question 40

Bardet-biedl syndrome (BBS)

Answer 40

and autosomal recessive disease, caused by SNVs and indells in one of 20 genes

Question 41

phenotypes of BBS (primary)

Answer 41

Rod cone dystrophy, polydactyly
obesity
genital anomalies
renal anomalies
learning difficulties

Question 42

phenotypes of BBS (Secondary)

Answer 42

speech delay
developmental delay
DM