Shared Flashcard Set

Details

Medical Genetics part II
8.25 at 8:30 by Dr. McGoey
105
Pathology
Professional
08/25/2011

Additional Pathology Flashcards

 


 

Cards

Term
What percent of single gene disorders manifest before puberty?
Definition
90%
Term
What is the percent incidence in the pediatric population?
Definition
.4%
Term
What are the five main categories of nontraditional inheritance?
Definition
1)imprinting 2) uniparental disomy 3) heritable unstable repeats 3) mitochondrial 4) mosaicism
Term
T/F Autosomal single gene disorders are more common than x linked single gene disorders.
Definition
true (90% autosomal, 10% xlinked)
Term
Adult-onset genetic disorders generally have what inheritance pattern?
Definition
autosomal dominant
Term
What do you call it when the same gene mutation can give you a very mild or very severe phenotype?
Definition
variable expressivity of the gene
Term
What do you call it when the mutation may or may not show up as on the phenotype?
Definition
incomplete penetrance of a genotype
Term
If parents have a child with a de novo mutation, their chances of having another child with denovo mutation is ___%.
Definition
<1%
Term
What do you call it when >1 gene can cause similar phenotype or the same syndrome?
Definition
genetic heterogeneity
Term
What are the different mutations that can cause polycystic kidney disease?
Definition
polycystin 1 (PKD1 on chrom 16) and polycystin 2 (PKD2 chrom 4)
Term
What do you look for in a pedigree to determine autosomal dominant inheritance?
Definition
vertical disease, males=females, male to male transmission possible, no carrier state
Term
What is the inheritance pattern of Marfan's syndrome?
Definition
autosomal dominant
Term
What are the skeletal signs of marfan's?
Definition
disproportionate tall stature, arachnodactyly, pectus excavatum, scoliosis, wrist/thumb sign
Term
What are the ocular signs of Marfan's?
Definition
myopia, upward lens dislocation
Term
What are the CV signs of Marfan's?
Definition
MVP (can present as anxiety), ascending aortic aneurysm/dissection due to cystic medical necrosis
Term
What mutation causes Marfan's? How do you get this mutation?
Definition
Fibrillin-1 (FBN1) gene on chromosome 15. 75% inherited; 25% de novo
Term
What is the prevalence of Marfan's?
Definition
1/5000
Term
What's another name for neurofibromatosis 1?
Definition
von Recklinghausens disease
Term
What are the signs of NF1?
Definition
cafe au laits, axillary freckles, neurofibromas, lisch nodules of iris, optic nerve glioma, learning disability (>50%), rarely: pheochromocytoma of adrenal medula
Term
What is the classic symptom of pheochromocytoma of the adrenal medula?
Definition
pheochromocytoma of adrenal medulla is usually benign but causes episodic hypertension
Term
What are the distinguishing characteristics of NF type 2? Where is the mutation?
Definition
bilateral acoustic neuromas and cateracts, less common, Merlin gene on chromosome 22
Term
What percent of polycystic kidney disease is due to PKD1 and which percent is due to PKD2?
Definition
PKD1 is 85% and PKD2 is <15%
Term
At what age do pts with ADPKD get chronic renal failure?
Definition
<60yoa
Term
What are the signs of ADPKD?
Definition
bilateral renal cysts, liver and pancreas problems, and circle of Willis verry aneurysms (causes death in 10% of patients)
Term
What are the signs of tuberous sclerosis?
Definition
skin: hypopigmented patches (ashleaf spots), subungual or nasolabial fibromas (adenoma sebaceum)
learning disability (>50%), seizures, autism
rarely: tumors of kidney (angiomyolipoma), heart (rhabdomyoma), brain (astrocytoma), lung (lymphangiomyoma)
Term
What genetic mutations cause tuberous sclerosis?
Definition
short answer: lots of different ones some we don't even know about
long answer: 60% tuberin (TSC2) gene, 20% hamartin, 20% TSC patients have no identifiable mutation.
2/3rds of cases are denovo
Term
What is the number 1 cause of genetic dwarfism?
Definition
achondroplasia
Term
What is the genetic mutation associated with achondroplasia?
Definition
fibroblast growth factor (FGFR3 gene) 4p, 80% de novo associated with advanced paternal age
Term
What is the mutation associated with sickle cell?
Definition
beta globin gene (chromosome 11). Single point mutation of a glutamic acid to valine causes abnormal beta subunit of hemoglobin and changes HbA to HbS (which is insoluble and deformed)
Term
What are the signs of sickle cell?
Definition
stroke, splenic infarct, dactylitis, priaprism, infections with encapsulated organisms, osteomyelitis, impotence, acute respiratory distress (acute chest syndrome), pulmonary HTN, pain crisis
Term
What's the rate of carriers for sickle cell in american blacks? african blacks?
Definition
1/12
1/4
Term
What are two classic presentations of cystic fibrosis?
Definition
recurrent sinopulmonary infections and failure to thrive
Male infertility due to absent vas deferens
Term
Where/what is the gene defect that causes cystic fibrosis?
Definition
CFTR gene on chromosome 7.
Term
What is the number 1 lethal genetic disease of caucasians?
Definition
CF
Term
What is the incidence of caucasians affected by cystic fibrosis?
Definition
1/3200
Term
What is the incidence of cystic fibrosis carriers among caucasians?
Definition
1/22
Term
What is the incidence rate of all of the inborn errors of metabolism combined?
Definition
1/5000
Term
Hunter's and Hurler's syndrome are examples of what kind of storage disease?
Definition
mucopolysaccharidoses, which is a lysosomal storage disorder
Term
Neimann-Pick, Tay-Sacchs, Gaucher, and Leukodystrophies are all types of what storage disease?
Definition
sphingolipidosis, a lysosomal storage disorder
Term
PKU, Homocystinuria, and MSUD are all due to what type of inborn error of metabolism?
Definition
amino/organic acidoses, of intermediary pathway defects
Term
Ornithine transcarbamylase is an inborn error of metabolism involving what biological process?
Definition
urea cycle
Term
LHON, MERRF, and MELAS are all types of what disorders?
Definition
mitochondrial disorders
Term
What molecules build up in mucopolysaccharide LSDs?
Definition
dermatan and heparan sulfate
Term
Describe symptoms/mutation/inheritance pattern of MPSI: Hurler syndrome.
Definition
autosomal recessive (alpha-iduronidase on chrom 4)
coarse, faces, mental and growth retardation, corneal clouding and death < 15 years due to "coronary artery disease"
Term
What is the missing enzyme of Hunter's syndrome? What is the inheritance pattern? How is it distinguishable from Hurler's?
Definition
iduronate sulfatase
XLR
milder disease with no corneal clouding
Term
What are the symptoms of Tay Sachs?
Definition
progressive MR, seizures, and blindness by 6 months; dealth before 4 yoa
Term
Where is the mutation/what is the enzyme of Tay Sachs? What is the product that builds up?
Definition
hexosaminidase A (HEXA) gene on chromosome 15
buildup of GM2 ganglioside
Term
Which populations are at risk for Tay Sachs?
Definition
1/27 Ashkenazi jews and 1/30 LA cajuns are carriers
Term
What is the prevalence of carriers in the jewish population for Gaucher? neimann pick?
Definition
gaucher= 1/18 jews
neimann pick= 1/90 jews
Term
What is the gene, enzyme, buildup product and symptoms of gaucher disease?
Definition
beta-glucocerebrosidase gene on chromosome 1
glucocerebroside buildup
HSM, bone necrosis and pancytopenia
Term
What is the gene, enzyme, buildup product, and signs of Neimann Pick
Definition
sphingomyelinase gene on chromosome 11
sphyingomyelin buildup
progressive neurologic decline, HSM, cherry red spot, death by 4 yoa
Term
Patients who present with a fair complection and a mousy/musty odor are typical of what genetic disorder?
Definition
Phenylketonuria
Term
People with PKU can't convert what?
Definition
phe into tyr
Term
What is the population prevalence of PKU in caucasians?
Definition
1/10,000 have the disease 1/50 are carriers
Term
What are the symptoms of an untreated person with PKU?
Definition
MR by 6 mo of age, microcephaly and seizures
Term
T/F X linked dominant disorders are a relatively common form of genetic disorders.
Definition
False, they are very rare
Term
What is the "decreased fertility phenomenon" associated with females affected by x linked dominant disorders?
Definition
affected females will have multiple stillbirths/miscarriages due to male fetuses incompatible with life
Term
Men with X linked dominant disorders are severely affected by x linked dominanat disorders due to male _______.
Definition
x-hemizygosity
Term
T/F Affected females with X linked dominant disorders are more common that affected males.
Definition
true! due to male deaths and no male to male transmission
Term
Vitamin D resistant rickets is due to a defect in which gene? What is the inheritance pattern? What is the mechanism of the disease?
Definition
phosphate endopeptidase (PHEX) gene which causes PO4 wasting from the proximal renal tubule
X linked dominant!
Term
What is the incidence of vitamin D resistant rickets?
Definition
1/20,000
Term
Males are affected by X linked recessive disorders due to ____.
Definition
x chromosome hemizygosity
Term
When/why do children with DMD die?
Definition
cardiomyopathy and respiratory failure in 20s
Term
What is the inheritance pattern of DMD?
Definition
x linked recessive
Term
What gene is mutated in DMD?
Definition
dystrophin gene
Term
What is the prevalence of DMD?
Definition
1/6000
Term
Hemophilia A is due to a deficiency in _____.
Definition
Factor VIII gene
Term
What is the inheritance pattern of hemophilia A?
Definition
x linked recessive
Term
Trinucleotide expansions below disease threshold are termed _____ while trinucleotide sequences above disease threshold are termed _____.
Definition
premutations
full mutations
Term
What is the trinucleotide repeat in huntington's?
Definition
CAG
Term
What is the trinucleotide repeat in spinocerebellar ataxia?
Definition
CAG
Term
What is the trinucleotide repeat with fragile X?
Definition
CGG
Term
What is the trinucleotide repeat with Friedrich's Ataxia?
Definition
GAA
Term
Most diseases due to heritable unstable repeats are due to what repeating trinucleotide?
Definition
CAG which codes glutamine so these are called polyglutamine diseases (8 of the 14 disorders of HUR are due to CAG repeats)
Term
What specific genetic abnormality causes Huntington's?
Definition
CAG expansion of more than 36 in the huntingtin (HTT) gene on chromosome 4
Term
Huntington's diseases is associated with what type of anticipation?
Definition
paternal
Term
What is the number 1 familial form of MR?
Definition
fragile x
Term
What are the signs/symptoms of fragile X?
Definition
MR, elongated face/ears, macroorchidism, autism, MVP
Term
What mutation causes fragile X disease?
Definition
more than 200 CGGs on the X chromosome
Term
Fragile X disease exhibits _______ anticipation.
Definition
maternal
Term
Describe the structure of mitochondrial genome.
Definition
single circular chromosome
Term
What three organs/tissues to mitochondrial diseases affect?
Definition
eyes, brain, and muscle
Term
What is heteroplasmy in the context of mitochondrial disease?
Definition
a mix of abnormal and normal mitochondrial DNA
Term
What do you look for in a pedigree to diagnose a mitochondrial disease?
Definition
M=F, mutligenerational, no male to male trnasmission
Term
What does MERRF stand for?
Definition
myoclonic epilepsy with ragged red fibers
Term
What does LHON stand for?
Definition
Leber's hereditary optic neuropathy
Term
What does MELAS stand for?
Definition
mitochondrial encephalopathy with lactic acidosis and stroke like episodes
Term
What does NARP stand for?
Definition
neuropathy, ataxia, retinitis pigmentosa
Term
What are the symptoms of Kearns Sayre Syndrome?
Definition
mitochondrial disease with ptosis, retinitis pigmentosis, and cardiomyopathy
Term
Do carrier females show symptoms for hemophilia A?
Definition
yes, they have mild bleeding tendencies
Term
What is mosaicism?
Definition
the presence of two, genetically different, cell lines in the same individual
Term
What do you call mosaicism when the mosaic line may be found in all types of tissues?
Definition
generalized
Term
What do you mosaicism that is only found in one organ system?
Definition
confined mosaicism (e.g. confied placental mosaicism)
Term
How is osteogenesis imperfecta inherited?
Definition
AD inheritance that is 95% de novo and 5% parental gonadal mosaicism
Term
Which type of OI is the perinatal lethal form?
Definition
type II
Term
What are the signs/symptoms of OI?
Definition
bony fractures, abnormal teeth, hearing loss, blue sclerae
Term
What is the most common type of modification responsible for genomic imprinting?
Definition
DNA methylation of a cytosine base
Term
When does genomic imprinting occur?
Definition
gametogenesis
Term
What are the signs/symptoms of Prader-Willi syndrome?
Definition
neonatal poor feeding and hypotonia with childhood hyperphagia, mental disability, hypogonadism, and small hands/feet. 10% are due to inherited paternal imprinting defect
Term
What characterizes Angelman's syndrome?
Definition
seizures, severe mental retardation, ataxia ("happy puppet"), spontaneous laugh
Term
What is uniparental Disomy?
Definition
when both chromosomes in a pair are inherited from one parent, and none is inherited from the other parent
Term
Beckwith-Wiedemann syndrome is characterized by...
Definition
LGA, macroglossia, omphalocele, hemihypertrophy, renal tumors
Term
What causes Beckwith-Wiedemann Syndrome?
Definition
20% by paternal UPD of chromosome 11
Term
What causes Prader-Willi?
Definition
10% paternal imprinting defect, 20% maternal UPD, 70% deletion in paternal chromosome (on chromosome 15)
Term
What causes Angelman's syndrome?
Definition
5% maternal imprinting defect, 20% paternal UPD, and 70% deletion in maternal chromosome (chromosome 15)
Supporting users have an ad free experience!