Genetics Flashcards
Gene mutation causing CHARGE syndrome
CHD7 gene
Features of Prader Willi syndrome?
Hyperphagia
Obesity
Short stature
Hypotonia
Hypogonadism
Mental retardation
Features of Angelman syndrome
Mental retardation
Seizures
Frequent smiling and laughing
Growth retardation
Genetic cause of Angelman syndrome?
15q12 is usually paternally imprinted (silence)
Disease when maternal copy of 15q12 is deleted (70%) paternal uniparental disomy (2%) or point mutation in the functional copy of UBE3A gene
Genetic cause of Prader Willi Syndrome
Maternal imprinting (silencing)
70% have deletion of the paternally derived 15q11-12
25% have maternal uniparental disomy
Pedigree rules for imprinting?
- Sex of the transmitting parent will always be the same across the pedigree (eg always a transmitting male)
Examples of triplet repeat expansion disorders?
Fragile X: CGG
Myotonic dystrophy: CTG
Friedreichs Ataxia: GAA (the only recessive one)
Huntingtons: CAG
What is the concept of ‘anticipation’ in genetics?
Applies to triplet repeat expansion disorders: earlier onset in subsequent generations
Features of Freidreich’s Ataxia
Early loss of vibration sense and proprioception
Ataxia of all 4 limbs
Hypo/arreflexia
Weakness (LL then UL)
Cerebellar dysarthria
What 3 features may be seen with fragile X pre mutation (50-200 CGG repeats)?
- Premature ovarian failure
- Fragile X tremor-ataxia syndrome
- Neurocognitive defects later in life
Risk of recurrence with gonadal mosaicism?
Usually low risk e.g. 1-2-3%
Which conditions increase with consanguinity?
Autosomal recessive
Examples of X-linked dominant conditions?
Incontinentia pigmenti
Rett syndrome
X-linked hypophosphatemic ricks (PHEX gene)
Difference between incomplete penetrance and expressivity?
incomplete penetrance = absent phenotype (even though mutation may be present)
Variable expressivity = disorder manifesting in different ways for those affected eg tuberous sclerosis
rules for mitochondrial disease inheritence?
Both sexes affected
Transmission only by females
What is ‘heteroplasmy’?
The presence of both normal and mutation-carrying mitochondrial DNA in a cell
What is a non-sense mutation
Replacement of codon with a stop codon
What is a mis-sense mutation
Mutation that results in an amino acid substitution (eg REPLACEMENT of a single nucleotide)
What is a frameshift mutation?
Abnormal amino acid sequence due to insertion or deletion which causes a shift in the reading frame
Which chromosomes are acrocentric (centromere off centre) and at risk of translocation?
Chromosomes 13, 14, 15, 21, 22
What does microarray not detect?
Inversions
Balanced chromosome configurations and insertions
How often does translocation occur to result in Down syndrome?
5% of cases are due to translocation, commonly between chromosomes 21 and 14
- problems arise at gametogenesis (not affected by maternal age) - risk of recurrence
Most common genetic mutations in CF?
delF508 (~80%)
G551D (2.6%)
G542X (1.5%)
G85E (1.5%)
Syndrome caused by Imprinting defect at 11p15/
Paternal uniparental disomy at 11p15
Beckwith Wiedemann
Syndrome caused by imprinting defect at 11p15, maternal uniparental disomy at 11p15 or 7q?
Russell Silver Syndrome
Features of Russel-Silver syndrome?
IUGR, short status, macrocephaly with triangular facies
Cafe au lait spots
clinodactytyl
Features of stickler syndrome?
Cleft palate/ PRS
Myopia, cataracts, retinal holes and detachments
SNHL
Joint hypermobilitya and MSK issues
Mitral valve prolapse
3 common features of congenital rubella syndrome?
Cataracts
PDA
Microcephaly
Examples of histone acetylation defects?
Cornelia de lange syndrome, Kabuki Syndrome, Rubinstein-Taybi syndrome
Examples of ribosomal trafficking defects?
Diamond blackfan anaemia, Schwachmann Diamond Syndrome, cartilage hair hypoplasia
Example of telomere maintenance defect?
Dyskeratosis congenita
Differences between Marfan syndrome and Loeys-Dietz syndrome?
In Loeys-Dietz:
- Bifid or broad uvula
- Hypertelorism
- Twisted arteries
- Aneurysms more common
Features of 16p13.11 microduplication?
- Autism
- Behavioural issues
- risk factor for neuropsychiatric diagnoses
- includes MYH11 gene which is associated with increased risk of aortopathy (aneurysms, dilatation)
Most common gene mutation in Alagille syndrome?
JAG 1 (89%)
NOTCH2 second most common
Macroglossia, exomphalos, lateralised overgrowth, hyperinsulinism, risk of Wilms, ears creases and/or pits, umbilical hernia
Beckwith Wiedeman syndrome
Features of Kabuki syndrome
CHD (70%) - usually L sided obstructive defects
Cleft lip/palate (30%)
ID/GDD
Genitourinary issues (25%)
Dysmorphism: arched eyebrows with eversion of lateral 1/2, depressed nasal tip, large cupped ears, long palpebral fissures
Joint hyper mobility
There is risk of sudden cardiac death with anaesthesia in which condition?
Williams Syndrome
Fibrillin-1 mutation (FBN1) is seen in which condition?
Marfan syndrome
Most common genetic cause for trisomy 21?
95% are due to non-disjunction during meiosis (failure of separation of chromosome homologues)
3-4% are due to translocation (commonly 14;21)
1-2% mosaicism
Recurrence risk for trisomy 21 caused by translocation?
12% if mother is carrier
1% if father is carrier
100% if 21;21 translocation
What is the risk of leukaemia in T21?
1 in 300 risk of ALL or AML for children with T21 (10-20 times increased RR)
