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Path - Chapter 5
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| Question | Answer |
|---|---|
| Loss of key structural protiens such as those seen in osteogenesis imperfecta are typically inhereted how? | Autosomal dominant (dominant negative effect seen here) |
| Gain of function mutations which can result in abnormal proteins that are toxic to tissues such as seen in Huntingtons is inherited how? | Autosomal Dominant |
| This is the largest category of mendelian disorders (autosomal dom, autosomal recessive, x-linked recessive)? | Autosomal recessive |
| Complete penetrance is common in Autosomal Dominant genes (T/F)? | False; seen more in autosomal recessive |
| A new mutation which is autosomal recessive will result in an asymptomatic or symptomatic child? | Asymptomatic |
| Von willebrand disease and spherocytosis is passed down in which pattern? | Autosomal dominant |
| What mendelian fashion is polycystic kidney disease passed down? | Autosomal Dominant |
| How is achondroplasia inherited? | Autosomal dominant |
| How are myotonic dystrophy and tuberous sclerosis inherited? | Autosmal dominant |
| lysosomal storage disease and wilsons are inherited how? | Autosomal recessive |
| hemochromatosis and congenital adrenal hyperplasia are inherited how? | Autosomal recessive |
| friedreich ataxia is inherited how? | Autosomal recessive |
| G6PD is typically inherited how? | X-linked recessive |
| Females heterozygotes of G6PD are predisposed to what under certain drugs such as malaria? | anemia |
| Vitamin D rickets is an example of what kind of inheritance? | X-linked dominant |
| Duchenne muscular dystrophy is inherited how? | X-linked recessive |
| Chronic granulomatous disease is inherited how? | X-linked recessive |
| Agammaglobulinemia and Wiskott-Aldrich are inherited how? | X-linked recessive |
| Lesch-Nyhan and fragile X are inherited how? | X-linked recessive |
| What are the 4 mechanisms for single gene mendelian disorders? | enzyme defects and consequences; defects in membrane receptors and transport systmes; alteration in structure and function and quantity of non-enzyme proteins; mutations involving unusual reactions to drugs |
| This is an autosomal dominant condition marked by disorders of connective tissues, manifested principally by changes in the skeleton, eyes, and cardiovascular system; an extracellular glycoprotein prevents proper deposition of tropoelastin. | Marfan Syndrome (Fibrillin-1_FBN1) |
| In marfan syndrome, what cytokine is upregulated due to loss of normal microfibril sequesteration. This can have deleterious effects on vascular smooth muscle development? | TGF-B (may lead to aortic dissection) |
| This patient is unusually tall with long fingers and toes; double jointed. His face has prominent supraorbital ridges and has a history of scoliosis. His chest has mild pectum excavatum, and eye exam reveals ectopia lentis. What is this? | Marfan Syndrome |
| What is the most life-threatening feature of patients with marfan syndrome? | Cardiovascular lesions (mitral valve prolapse and dilation of aorta) |
| This group of disorders result from some defect in the synthesis or structure of fibrillar collagen? | Ehler-Danos (both autosomal dominant and Autosomal recessive) |
| Contortionist typically have hyperextensibel skin and their joints are hypermobile as well as vulnerable to trauma, what conditions do they normally have? | Ehlers-Danos |
| Which Ehlers Danos display Autosomal Recessive inheretibility and why? | Kyphoscoliosis type 6 (lysyl hydroxylase deficiency) and Dermatosporaxsis type 7b (due to procollagen N-peptidase) |
| This ehlers-danos syndrome results due to improper cross-linking of the collagen fibers? | Kyphoscoliosis type 6(lysyl hyrdoxylase) |
| This type of Ehlers Danos results in abnormalities in type 3 collagen (a structural protein) and may result in arterial and uterine rupture | Type 3 vascular |
| Which two ehlers-danos result from poor conversion of procollagen to collagen? | Both type 7 (arthrochalasia and dermatosporaxis) |
| This Ehlers Danos type results from Collagen 5 gene defect and results in easy bruising, skin and joint hypermobility, and bruising | |
| This Autosomal Dominant disease is a result of a defect in the LDL receptor, which is involved in transport and metabolism of cholesterol? | Familial Hypercholesterolemia |
| T/F homozygotes of familial hypercholesterolemia are more severly effected than heterozygotes? | TRUE (more LDL receptors are affected) |
| What is the immediate and major precursor of LDL? | IDL |
| What are two ways of removal of LDL from the plasma? | LDL receptor and Scavenger receptor (macrophages) |
| What three processes are affected by intracellular cholesterol? | Cholesterol inhibits HMG Coa reductase (rate-limiting step in cholesterol synthesis); Activates acyl-coenzyme A:cholesterol acyltransferase; suppresses synthesis of LDL receptors |
| Breifly describe the 5 classes of mutations affecting Familial Hypercholesterolemia? | Synthethsis (uncommon); transport (fairly common- cant make it to the golgi); binding (@ cell surface but can't bind LDL); clustering (bind normally but can't localize in coated pits); recycling (trapped in endosome, cant get back to the surface) |
| What is the basic pathogenesis of lysosomal storage diseases? | lysosomal enzyme defects; cant break down certain molecules; lysosomes get enlarged and interfere with cellular functions |
| What are three strategies of lysosomal storage diseases? | enzyme replacement; substrate reduction; molecular chaperone therapy (as in Gaucher_ try and help the unfolded protein) |
| What is the locational difference between defects in gangliosidases and mucopolysacharridases? | Gangliosidases are only in the CNS while the other is found everywhere |
| A mutation of the alpha subunit locus on chromosome 15 results in a sever deficiency of hexoaminidase A in this disease? | Tay-Sachs (build up of GM2) |
| Involvement of which parts of the body dominate the clinical picture of Tay Sachs Disease? | Neurons in central and autonomic nervous systems and the retina |
| A patient diplays cytoplasmic inclusions which look like onion-skin layers within neuronal lysosomes, what is a likely diagnosis? | Tay Sachs Disease |
| What is a characteristic optical finding in tay sach disease and some other nueronal lysosomal storgae diseases? | Cherry red spot in the macula |
| Describe the clinical course of Tay Sachs? | manifests at age 6 months, deterioration and vegetattion @ age 1-2yrs, and then death @ 2-3 yrs |
| An inherited defieciency of sphingomyelinase is typicall of these two diseases? | Niemann Pick Disease type A and B |
| Which Niemann Pick disease has a worse prognosis (A or B) | Type A (early death within the first 3 years) |
| What is the pathophysiology Niemann Pick type A? | build up of sphyngomyelin in the mononuclear phagocyte lysosomes causes foaminess and enlargement, cells are widely distributed but spleen: enlarged, brain: gyri are shrunken and sulci are widened, leading to cell death and loss of brain substance |
| The most frequent form of this lysosomal storage disease presents at childhood and is marked by ataxia, vertical supranuclear gaze palsy, dystonia, dysarthria, and psychomotor regression; it is caused by a primary defect in lipid transport | NPC (nieman pick disease C) |
| Deficiencies in glucocerebrosidase encompass this group of autosomal recessive disorders? | Gaucher Disease (most common LSD) |
| These cells result from a build up of glucocerebrosides and display a fibrillary type of cytoplasm likened to crumpled tissue paper? | Gaucher cells (distended phagocytic cells) |
| What is the most common form of Gauchers? | Type 1 (chronic non-neuronopathic) limited to mononuclear phagocytes throughout the body but not the brain |
| T/F Presentation of Gauchers first starts in adults and are related to splenomegaly and bone involvement | TRUE; type is compatible with long -life |
| All Mucopolysaccharidoses are inherited as Autosomal recessive except for one, which one? | Hunters Syndrome (X-linked recessive) |
| This lysosomal storage disease is a progressive disease characterized by coarse facial features, clouding of the cornea, joint stiffness, and mental retardation? | Mucopolysaccharidoses |
| Which cells of the body display accumulated mucchopolysaccharides in MPS? | mononuclear phagocytes, endothelial cells, intimal smooth muscle cells, fibroblasts |
| Acid-schiff positive material accumulates in the lysosome producing an apparent clearing of the cytoplasm leading to formation of balloon cells? | Mucopolysaccharidoses |
| Lamellated zebra bodies are seen in replaced lysosomes within neurons of these two disease? | Nieman Pick and Mucopolysaccharidoses |
| What are the COMMON threads that run through all of the MPS? | hepatosplenomegaly, skeletal deformities, valvular lesions, subendothelial arterial deposits (coronary arteries), lesions in the brain |
| What are the important causes of death in MPS | myocardial infarction and cardiac decompensation |
| How do hurler (MPS1) syndrome and hunter syndrome (MPS2) differ? | Hunters has no corneal clouding, is X-linked, and is milder clinically |
| What are the three major subgroups of glycogen storage diseases? | hepatic forms (Von Gierkse glucose-6-phosphatase, deficient degradation of glycogen); Myopathic (McArdles muscle phsophorylase_ muscle cramps and elevated lactate levels post-workout); Acid Maltase and lack of branching enzyme (POMPE_cardiomegaly) |
| A lack of homogentisic oxidase characterizes this disease, where there is a build up of homogentisic acid which is excreted and imparts a black color to the urine? | Alkaptonuria |
| Ochronosis is found in Alkaptonuria, what is it? | dark pigmentation caused by binding of homogentisic acid to collagen of connective tissues, tendons, and cartilage |
| What is the most serious consequence of ochronosis in alkaptonuria? | Deposits within the articular cartilage of joints leading to loss of resiliency and becoming brittle and fibrillated |
| Deficiency with Glucose 6 phosphatase is characteristic of this disease? | Von Gierke Disease |
| Deficiency of muscle phosphorylase is found in this disease? | McArdle Syndrome |
| A deficiency in lysosomal acid maltase leads to this disease? | Pompe Disease |
| In these patients with a glycogenoses, there is hypoglycemia, hyperlipidemia, bleeding defieciency, and hepatomegaly and renomegaly? | Von Gierkes |
| Patients with this disease have painful cramps associated with strenous exercise, elevated lactate and creatine kinase, and myoglobinuria in 50% of cases? | McArdle Syndrome |
| Patients with this glycogenosis present with massive cardiomegaly, muscle hypotonia, and cardiorespiratory failure? | Pompes Disease |
| What are the two usual causes for aneuploidy? | non-disjunction and anaphase lag |
| What is the result of nondisjuntion? | one trisomic cell and one monosomic cell |
| What is the result of anaphase lag? | One normal cell and one monosomic cell |
| This is the MOST common of the chromosomal disorders and is the major cause of mental retardation? | Trisomy 21 (1/700) |
| What is the most common cause of trisomy 21? | Meitoic non-disjunction |
| Which parent is the extra chromosom in trisomy 21 usually from? | Maternal (non-disjunction occurs in the ovum of elderly women) |
| What results if there is a mitotic non-disjunction of chromosome 21 during early stages of embryogenisis (as it applies to Down Syndrome)? | Mosaicism (maternal age is of no importance) |
| What are the classic diagnostic clinical features of trisomy 21? | flat facial profile, oblique palpebral fissures, epicanthic folds |
| What is responsible for the majority of deaths in infancy and early childhood in patients with trisomy 21? | Congenital heart disease (ASD, AVD) |
| What do trisomy 21 children have a 10-20 increased risk of developing? | Acute leukemia (acute megakaryoblastic leukemia) |
| Trisome 21 patients older than 40 develop what? | Neurological disorders characteristic of Alzheimer disease |
| This baby has low set ears, micrognathia, and rocker bottom feet, he will develop mental retardation, what is a possible diagnosis? | Edwards (trisomy 18) |
| This baby is born with a cleft lip and palate, microphthalmia, polydactyly, and microcephaly? | Patau Syndrome (trisomy 13) |
| These two syndromes are a result of deletion of 22q11.2 gene? | DiGeorges Syndrome and Velocardiofacial syndrome |
| A patient with thymic hypoplasia and hypocalcemia comes in, genetic testing reveals a deletion of 22q11.2? | DiGeorges Syndrome |
| This disease is characterized by facial dysmorphism (prominent nose and retrognathia), cleft palate, cardiovascular anomalies and learning disabilities? | Velocardiofacial syndrome |
| Patients with velocardiofacial syndrome and DiGeorge are at a particular high risk of developing what other problems? | Psychotic illness (schizo and bipolar + ADHD) |
| What does XIST do? | A gene producing a noncoding RNA which coats the X-chromosome inactivating it |
| T/F the higher the number of X xhromosomes, the greater the likelihood of mental retardation? | TRUE; |
| This condition results in male hypogonadism when there are two or more X chromosomes, males have an elongated body, lack secondary sexual features, and are predisposed to type 2 diabetes and metabolic syndrome? | Klinefelter Syndrome XXY |
| What is the molecular reason for hypogonadism in Klinefelter if There is Y and X? | Non-random inactivation of the X with the shorter CAG repeat on the gene with the androgen receptor |
| This disorder is a result of monosomy of the X chromosome, and results in hypogonadism of the phenotypic female, short stature, coarctation of the aorta, and webbing of the neck, as well as failure of developing normal secondary characteristics? | Turner Syndrome |
| Streak ovaries, short stature (loss of SHOX gene), coarctation of the aorta? | Turners |
| What is the single most important cause of primary amenorrhea? | Turners |
| What are some of the concurrent debilitating processes that some turners patients possess or aquire? | hypothyroidism (autoantibodies); glucose intolerance; obesity; insulin resistance (worsened by growth hormone therapy) |
| Congenital adrenal hyperplasia can lead to what sex related disorder in females? | psuedohermaphroditism (early exposure of androgens virilizes external genitalia) |
| What is the most common cause of male pseudohermaphroditism? | complete androgen insensitivity syndrome (x-linked recessive) |
| What are the two distinct types of trinucleotide repeat disorders? | Coding (polyglutamine diseaseas) and Non coding |
| Trinucleotide repeats disorders which involve a gain of function, toxic metabolite production, or protein misfolding and aggregation leading to intranuclear inclusions are seen in the (coding/non-coding) types? | Coding |
| Fragile X syndrome, friedrich ataxia and myotonic dystrophy are part of which class of trinucleotide disorders (coding or non-coding)? | Non coding (loss of function; wide systemic effects) |
| This disorder is the 2nd most common cause of mental retardation; more prevalent in males; defected FMR1; Long face with large mandible, large everted ears, large testicles, hyperextensible joints, and mitral valve prolapse also seen? | Fragile X |
| This feature is found in 90% of males with Fragile X? | Macro-orchidism |
| Fragile X displays anticipation, what is this? | disease worsens with each successive generation |
| What causes expansion of repeats in fragile X (spermatogenesis or oogenesis)? | Oogenesis (female progeny have a greater chance of getting) |
| What is the molecular basis of Fragile X? | FMRP defect (brain and testis) a reduction of FMRP results in INCREASED translation of the bound mRNA at synaptic junctions |
| What kind of inheritence does Leber hereditary optic neuropathy display? | Maternal (mitochondrial) |
| Mental retardation, short stature, hypotonia, small hands and feet, and a deletion of a small area of the paternal chromosome 15? | Prader Willi |
| This patient has had history of seizure, walks in with an ataxic gait, and laughs inappropriatly. Where is his genetic abnormality found? | Chromosome 15 (maternal)__Angelman |
| If a person inherits both copies of chromosome 15 from the mother, they will have what syndrome? | Prader Willi |
| If a person inherits both copies of chromosome 15 from the father, what are some likely symptoms? | mental retardation, ataxic gait, and innapropriate laughter (AngelMan) |
| What gene is affected in Angelman syndrome? | Ubiquitin Ligase |
| What is a possible explanation of a phenotypically normal parent (couple) to have more than one affected child (assuming autosomal dominance)? | Gonadal Mosaicim (a new mutation only affecting the germ line will be passed on but will not affect the carriers) |
| If the disease-associated gene is known, what is the method of choice for detection of the causative mutation? | Direct sequencing (if you don't know, use linkage analysis with markers such as SNP) |
| Describe a typical GWAS study? | take HAPMAP and select SNPs > make SNP chip > compare DNA from individuals With and Without trait > ID over-repressented SNPS > find candidate gene and do secondary study |
| This technique involves looking at DNA and although rarely used still is useful for Fragile X like diseases? | Southern Blotting |
| What technique hybridizes flourescently labeled probes to entire metaphase fixed chromosomes? | Chromosome painting (FISH) |
| The study of certain modification of DNA such as methylation and acetylation is termed? | Epigenetics |
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