Genetic Modes Of Inheritance Flashcards
Who do x linked disorder occur most severe in
Males
What type of disorder is duchenne muscular dystrophy? Why type of abnormality is it?
X linked, out of frame deletion so dystrophin is not functional
What type of disorder is Becker muscular dystrophy? Why type of abnormality is it?
X linked, in frame deletion
What is an out of a frame mutation
Deleted message does not fit together
What is an in frame mutation
Deleted message fits together
What type of disorder is hemophilia?
X linked
What happens in hemophilia
Clotting doesn’t happen as it should. Missing factor eight? A missing factor nine? B
What is Becker muscular dystrophy
Allelic form, less severe, occurs later in life
Clinical manifestations of duchenne muscular dystrophy
Passed away from heart and lung complications, need wheelchair by age 13, males show weakness early on, difficulty getting off the floor, calf hypertrophy
What type of disorder is menkes syndrome/ kinky hair syndrome
X linked
Clinical features of menkes syndrome/kinky hair syndrome
Abnormal/sparse kinky hair, hypotonic, seizures, failure to thrive, motor loss, usually die by age 3 but those who survive are disabled
Mike menkes?
Some function of the protein still there so clinical manifestations are not as severe
What happens to males in menkes syndrome/kinky hair syndrome
They do not reproduce
What is haldanes syndrome in kinky hair syndrome?
Affected males do not reproduce but disease incidence stays the same every year. This means that 1/3 of cases each year are new mutations
In what disorder is there a copper transport ATPase error leading to low copper and ceruloplasmin
Menkes disorder
Who is most affected in X-linked recessive disorders where the mother is the carrier
Males because they only have one copy of the X. Daughters can only be carriers
How are daughters affected in excellent recessive disorder’s where the father is affected? Sons?
all daughters are carriers and all sons are unaffected
Is there male to male transmission in X-linked recessive disorders?
No
As is there make to make transmission in x linked dominant disorders
No
Where is there vertical transmission?
X linked dominant disorders
What happens if males are affected in x linked dominant disorders
Males are not affected bc you get a miscarriage
What type of disorder is hypophosphatemic rickets
X linked dominant male lethal
Clinical manifestations of hypophosphatemic rickets
Bowing of lower extremities
Clinical manifestations of aicardi syndrome
agenesis of corpus callosum, distinctive chorioretinal lacunae (lakes in retina)
Type of disorder of aicardi syndrome
X linked dominant male lethal
Clinical manifestations of incontinentia pigmenti
Affects hair skin nails teeth (ectoderm) , seizures, cognitive delay, retinal detachment
Type of disorder of incontinentia pigmenti
X linked dominant male lethal
What disorder has 4 stages
Incontinentia pigmenti
4 stages of incontinentia pigmenti
Blistering
Wart like rashes
Swirling, macular, hyperpigmentation
Lines of lashko, linear hypopigmentation, mimic Christmas tree
Type of disorder of rett syndrome
X linked dominant male lethal
Clinical manifestations of Rett syndrome
Microencephalopathy, regression, seizures, hand wringing
What happens with the transmission in y linked disorders
Male fathers pass to all sons
What are sex limited disorders
Disorders where it will only affect one sex such as breast cancer
What are sex influence disorders
Disorders where both sexes can have the disorder but will express it in different ways such as pattern baldness
Who passes mitochondrial inheritance on
Females only
is there a high mutation rate in mitochondrial inheritance
Yes because there is no repair mechanism
What is heteroplasmy
Some mitochondria I have mutations in some don’t. May not reach threshold so some people are asymptomatic
What is Homoplasmy
Mutations in all mitochondria so high likelihood of symptoms
What does MELAS stand for
Mitochondrial encephalopathy, lactic acidosis, stroke like episode
Symptoms of MELAS?
Seizures, headaches, vomiting, 2 to 10 years old
What type of disorder is MELAS
Mitochondrial inheritance
What type of disorder is MERRF
Mitochondrial inheritance that is heteroplasmy
What does MERRF stand for
Myoclonic epilepsy with ragged red fibers
What type of mutation is MERRF?
Point mutation
Clinical manifestations of MERRF
Ataxia, dementia
What type of disorder is LHON
Mitochondrial inheritance
What does LHON stand for
Leber hereditary optic neuropathy
Clinical manifestations of LHON
Sudden blurred vision in adulthood beginning with one eye
What type of mutation is LHON
3 Point mutations all with different penetrancd
Are more males or females affected in LHON
Males
What is penetrance
Either have the symptoms or don’t; 100% means you have all the symptoms
What is variable expressitivity
Severity of symptoms
What is vertical transmission
Inheritance is in every generation
If there is vertical transmission what type of disorder is it? What if there is no vertical transmission?
Yes- dominant
No- recessive
If there is only male to male transmission what type of disorder is it? What if it’s not?
Yes- y linked
No- not y linked
What type of disorder is it if only one sex is affected? What if not?
Yes- x linked
No- autosomal
What if affected mothers have unaffected kids?
Yes- not mitochondria
No- mitochondrial
Epigenetic factors?
methylation; some genes on at certain times and some off
Are there mutations at the nucleotide level in epigenetic factors
No
What type of disorder is Prader willi syndrome PWS
Genomic imprinting; deletion of paternal 15 q
What disorder has early feeding problems then hyperphagia
PWS
Clinical manifestations of PWS
Short, intellectual disability, behavioral problems, hypogonadism
MC genetic causes obesity?
PWS
What disorder is also called happy puppet
Angelman syndrome (AS)
Clinical manifestations of AS
Small head, arm flapping, ataxia, inappropriate laughter, no speech, intellectual disability
What type of disorder is Angelman syndrome
Genomic imprinting 15 q deletion of maternal
What is the chromosome difference in Beckwith Weidman syndrome (BWS)
P 11 methylation defect
Clinical manifestations of beckwith Weidman syndrome (BWS)
Overgrowth, enlarged tongue, body, and organs , body asymmetry, abdominal wall defects, hemangiomas, earlobe crease
What are the clinical manifestations of Russell silver syndrome (RSS)
Undergrowth, intrauterine growth, retardation, triangular faces, finger clinidactyly, abnormal sweating, body asymmetry
Dynamic mutations?
Repeat become unstable after certain number of repeats
Anticipations?
Larger repeats so symptoms are early onset and more severe
Premutations?
Repeat size length are more than normal but they have less than the disease state
What type of disorder is myotonic dystrophy
Autosomal dominant, triplet repeat disorder
What type of disorder is congenital myotonic dystrophy
Autosomal dominant, triplet repeat disorder with more expansions than myotonic alone
What type of disorder is Huntington disease
Autosomal dominant, Triple repeat of CAG
Clinical manifestations of myotonic dystrophy
Myotonia, Face muscle atrophy and weakness, cataracts, heart condition, low IQ
What is myotonia
Can’t release grip
Clinical manifestations of congenital myotonic dystrophy
Severe hypotonia, failure to thrive, intellectual disability
Clinical manifestations of Huntington disease
Decreased motor control, drunk movements, changing mood, memory trouble
What type of disorder is fragile X syndrome
X linked, trinucleotide repeat of FMR1 gene
What do the symptoms vary based on in fragile X syndrome
Number of repeats like pre-mutation or full mutation
Who is fragile X more common in males or females?
Females
What is the most common inherited form of intellectual disability
Fragile X syndrome
Clinical manifestations of fragile X syndrome
Long face, protruding ears, autistic behavior, intellectual disability
What causes Russell silver syndrome (RSS)
Most ppl have 11P15.5 methylation defects, others have a maternal uniparental disomy of chromosome 7, the rest is unknown
