Term
| What percent of single gene disorders manifest before puberty? |
|
Definition
|
|
Term
| What is the percent incidence in the pediatric population? |
|
Definition
|
|
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
|
|
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
|
|
Term
| What do you call it when >1 gene can cause similar phenotype or the same syndrome? |
|
Definition
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
Term
| What is the incidence of caucasians affected by cystic fibrosis? |
|
Definition
|
|
Term
| What is the incidence of cystic fibrosis carriers among caucasians? |
|
Definition
|
|
Term
| What is the incidence rate of all of the inborn errors of metabolism combined? |
|
Definition
|
|
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
|
|
Term
| LHON, MERRF, and MELAS are all types of what disorders? |
|
Definition
|
|
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
|
|
Term
| People with PKU can't convert what? |
|
Definition
|
|
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
|
|
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
|
|
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
|
|
Term
| What gene is mutated in DMD? |
|
Definition
|
|
Term
| What is the prevalence of DMD? |
|
Definition
|
|
Term
| Hemophilia A is due to a deficiency in _____. |
|
Definition
|
|
Term
| What is the inheritance pattern of hemophilia A? |
|
Definition
|
|
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
|
|
Term
| What is the trinucleotide repeat in spinocerebellar ataxia? |
|
Definition
|
|
Term
| What is the trinucleotide repeat with fragile X? |
|
Definition
|
|
Term
| What is the trinucleotide repeat with Friedrich's Ataxia? |
|
Definition
|
|
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
|
|
Term
| What is the number 1 familial form of MR? |
|
Definition
|
|
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
|
|
Term
| Describe the structure of mitochondrial genome. |
|
Definition
| single circular chromosome |
|
|
Term
| What three organs/tissues to mitochondrial diseases affect? |
|
Definition
|
|
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
|
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
|
|
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
|
|
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
|
|
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) |
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