Genetics - Final - Diseases and Conditions - Part 2

davidwurbel7's version from 2015-04-22 05:14


Question Answer
Deficiency in the enzyme cystathionine β-synthaseHomocystinuria
Inframedial Dislocation of the lens, Mental retardation, Osteoporosis, Long bones, tight bones, Thromboembolism of the veins and arteries.Homocystinuria
Disease that can be due to a deficiency of methionine synthase, and cofactor deficiencies.Homocystinuria
Some disorders directly affect methyl-B12 formation. Cobalamin intestinal absorption is abnormal in some patients. Other patients have abnormalities in the major extracellular transport protein, transcobalamin II. Homocystinuria
Vitamin B6 (pyridoxal phosphate, Vitamin B12 & Folate deficiencies can lead toHomocystinuria
What TWO diseases results from deficiency in Iduronosulfate SulfataseHunter Syndrome (MPS 2 ) & Scheie Syndrome
Skeletal changes, hepatosplenomegaly, coarse facies, hearing loss, clear eyesHunter Syndrome
Corneal clouding, skeletal changes, hepatosplenomegaly, coarse facies, hearing loss, profound mental retardation, linear growth stops at 3 years old and death before the age of 10 years due to cardiorespiratory failureHurler Syndrome
Deficiency in Alpha-L IduronidaseHurler Syndrome (MPS 1 H)
In some cases, mutations in PAH result in a phenotypically mild form of PKU calledHyperphenylalanemia
Unusual facial features, Skeletal changes, Severe growth retardation, Mental retardation, Many of the acid hydrolases are found in excess in body fluids, Affected children typically survive for only 5 to 7 years I-Cell Disease
Mannose 6-phosphate deficiencyI-Cell Disease
Loss of Glycosylation is seen in what diseaseI-Cell Disease
Golgi-specific N-acetylglucosamine-1- phosphotransferase deficiency leads to a defect in protein traffickingI-Cell Disease
Defect in the enzymes that end up in the lysosome, that are targeted by the addition of mannose subunits that get phosphorylated.I-Cell Disease
Results from mother failing to adhere to a diet with no phenylalanine. Microcephaly, mental retardation, growth impairment, and heart malformations.Maternal Phenylketonuria
What kind of anemia can be seen in homocystinuriaMegaloblastic Anemia
Loss of of this enzyme results in mental retardation, organ damage, unusual posture, and in cases of maternal PKU, can severely compromise pregnancy. Phenylalanine Hydroxylase (PAH)
What converts phenylalanine to tyrosine by hydroxylating the phenolic ringPhenylalanine Hydroxylase (PAH)
Is due to the absence of phenylalanine hydroxylase (PAH) activity in the liver (LIVER is NOT damage), but the brain is damaged by the high blood levels of phenylalaninePhenylketonuria (PKU)
Damages the developing central nervous system in early childhood and interferes with the functioning of the mature brain. Developmental delay apparent in infancy, microcephaly, seizures, hyperactivity, and behavioral disturbances.Phenylketonuria (PKU)
Caused by mutations in both alleles of the PAH gene on chromosome 12Phenylketonuria (PKU)
In PKU, some phenylalanine is metabolized to ________ which is excreted in the urine causing a musky smell in the diaperPhenylpyruvic acid (a keto acid)
Mutation of the HexB gene, and production of a defective β- subunit, leads to inactivation of both hexosaminidase A and B activity. This disease is indistinguishable from Tay-Sachs diseaseSandhoff Disease
Deficiency in Hexosaminidase-Alpha SubunitTay-Sachs Disease (GM2 Gangliosidosis)
A prominent red fovea centralis surrounded by a pale macula is found inTay-Sachs disease (Cherry-red spot in the retina)
The effects of neuronal cell death can be seen directly in the form of the so-called cherry-red spot in the retina.Tay-Sachs Disease
Lower motor neuron dysfunction and ataxia due to spinocerebellar degeneration, but unlike the infantile disease, vision and intelligence usually remain normal, psychosis develops in one third of these patientsTay-Sachs Disease (Later Onset Variants)
Caused by mutations in the gene encoding porphobilinogen (PBG) deaminase (PBGD) on chromosome 11. Acute Intermittent Porphyria
Mental disturbance, Confusion, Emotional upset, Hallucinations and psychosisAcute Intermittent Porphyria
Characterized by elevated levels of plasma lipids (cholesterol, triglycerides, or both) and specific plasma lipoproteins. Clinical significance because of their role in atherosclerosis, often leading to myocardial infarction, a major cause of death and disability.Familial Hypercholesterolemia (FH)
Mutation in the Low-density lipoprotein (LDL) receptorFamilial Hypercholesterolemia (FH)
Mutation in LDL Receptor, Apoprotein B-100, PCSK9 Protease, ARH Adaptor ProteinFamilial Hypercholesterolemia (FH)
Xanthomas (cholesterol deposits in skin and tendons) are associated with Familial Hypercholesterolemia (FH)
Premature heart disease as a result of atheromas (deposits of LDL-derived cholesterol in the coronary arteries). Arcus corneae (deposits of cholesterol around the periphery of the cornea). The homozygous condition is more severe than the heterozygous condition.Familial Hypercholesterolemia (FH)
The most common inherited spinocerebellar ataxia and is an autosomal recessive disease also characterized by cardiomyopathy and type 2 diabetesFriedreich Ataxia
Defect is in expression of the frataxin gene due to expansion of GAA in intron 1, the GAA repeats result in the inhibition of transcriptional elongationFriedreich Ataxia
Frataxin gene mutation, Normal GAA repeats <34, uninterrupted 36 -100, affected >100Friedreich Ataxia
Normal CAG (Glutamine) repeats <35, unstable repeats 36-39, affected individuals have >40 repeatsHuntington Disease
The CAG repeat expansion results in an elongated polyglutamine tract in the protein. The expansion confers a novel function on the protein encoded by the huntingtin geneHuntington Disease
Presence of insoluble aggregates of the mutant protein in nuclear inclusions.These inclusions may actually be protective as it is the soluble nonaggregated form of the mutant protein that promotes abnormal interactions between the polyglutamine tract and a number of transcriptional regulators to alter the transcription of many genesHuntington Disease
Neurofibrillary tangles composed of hyperphosphorylated tau protein are locatedIntracellularly in Alzheimer Disease neurons
Some forms of heteroplasmy sporadically occur in certain mitochondrial syndromes _____ , _______ and these deletions ARE NOT typically maternally inheritedKearns-Sayre Syndrome and Pearson Syndrome
Large Deletions. Progressive myopathy, progressive external ophthalmoplegia of early onset, cardiomyopathy, heart block, ptosis, retinal pigmentation, ataxia, diabetesKearns-Sayre Syndrome (KSS)
Early onset progressive neurodegeneration with hypotonia, developmental delay, optic atrophy, and respiratory abnormalities. Mutations in the complex 5 ATP synthase 6 gene of the mitochondria.Leigh Syndrome
Mitochondrial disorders that are HomoplasmyLeber Hereditary Optic Neuropathy & Deafness
Substitution Mutation in the ND1 (more severe) & ND4 subunit of Complex 1 of the electron transport chainLeber Hereditary Optic Neuropathy
Rapid, painless bilateral loss of central vision due to optic nerve atrophy in young adults. Some recovery of vision depending on the mutation. This mtDNA Diseases is MultifactorialLeber Hereditary Optic Neuropathy (LHON)
Mutation in the Complex 5 genes of the mitochondrial DNALeigh Syndrome Mutation
Which sex is shown to have a higher penetrance for Leber’s Hereditary Optic NeuropathyMales (50%) vs females (10%)
Point mutations in tRNAleu(UUR) @ Position 3243 of mtDNAMELAS
Myopathy, Mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes; may present only as diabetes mellitus and deafness. loss of intellectual function (dementia)MELAS
Childhood symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, abdominal pain, and seizures. Most affected individuals experience stroke-like episodes beginning before age 40. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines.MELAS
Multisystem disorder characterized by myoclonus, which is often the first symptom, followed by generalized epilepsy, ataxia, weakness, and dementia.MERRF
Onset is usually in childhood, occurring after normal early development. Common findings are hearing loss, short stature, optic atrophy, and cardio-myopathy with Wolff-Parkinson-White (WPW) syndrome. Occasionally pigmentary retinopathy and lipomatosis are observed.MERRF
The following four "canonical“ features: myoclonus, generalized epilepsy, ataxia, and ragged red fibers in the muscle biopsy.MERRF
DMPK gene mutation. CTG (3’ UTR) repeatsMyotonic Dystrophy 1
CTG normal repeats <30, mildly affected 50-80 and affected 80-2000Myotonic Dystrophy 1
Expansion of CTG is located in the 3’ UTR. Cardiac conduction defects, Testicular atrophy, Insulin resistance, Cataracts, Also a congenital form with mental retardationMyotonic Dystrophy 1
The most common mutation in over 80% of affected individuals, is an A-to-G transition at nucleotide 8344. The mtDNA gene encoding the tRNALys is the gene most commonly associated with this disorderMERRF (Myoclonic epilepsy with ragged red fibers)
Management. Treatment of manifestations: conventional antiepileptic drugs for seizures; physical therapy to improve any impaired motor function; aerobic exercise; standard pharmacologic therapy for cardiac symptoms. Other: Coenzyme Q10 and L-carnitine supplements are often used in hopes of improving mitochondrial function. This treatment is used for which disorderMERRF (Myoclonic epilepsy with ragged red fibers)
Point mutation in tRNAlys @ Position 8344 of mtDNAMERRF
LHON-Leber’s hereditary optic neuropathy; MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes); MERRF (Myoclonic epilepsy with ragged red muscle fibers). NARP; Leigh Syndrome. They are characterized by ragged red muscle fibers. These are examples ofMitochondrial Diseases
A close genocopy of myotonic dystrophy 1 results from an expansion of the tetranucleotide CCTG in the the first intron of the zinc finger protein 9 geneMyotonic Dystrophy 2

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