Flashcards in 6. Genetic Disorder Deck (80):
What is a Robertsonian translocation?
Defined as translocation involving two acrocentric chromosomes with the break points occuring close to the centromers. This results in an extremely large chromosome and a tiny one, which is typically lost.
What disease is the most common of the chromosomal disorders?
What is the most frequent cause of Down syndrome?
Meiotic nondisjunction (95%).
What are Brushfield spots?
Speckled appearance of the iris that is associated with Down syndrome; not always present.
What is the karyotype of Edward syndrome?
Trisomy 18. 47XX or XY +18.
What is the cause of Edward syndrome and what are five clinical signs?
Nondisjunction; I. Mental Retardation. II. Low set earts and micrognathia. III. Congenital heart defects. IV. Overlapping flexed fingers. V. Rocker-bottom feet.
What is the karyotype of Patau syndrome?
Trisomy 13. 47XX or XY+13.
What is the cause of Patau syndrome and what are six clinical signs?
Nondisjunction; I. Mental Retardation. II. Cleft lip and/or palate. III Cardiac defects. IV. Renal abnormalities. V. Microcephaly. VI. Polydactyly.
What is the karyotype of Cri du Chat syndrome?
46XX or Xy, 5p-.
What is the cause of Cri du Chat syndrome and what are four clinical signs?
Deletion of the short arm of chromosome 5; I. characteristic high pitched cat-like cry. II. Mental retardation. III. Congenital heart diseae. IV. Microcephaly.
What is the cause of retinoblastoma?
Microdeletion of 13q14.
What is the cause of Wilm tumor?
Microdeletion of 11p13.
What is the karyotype of Klinefelter syndrome and what is the cause?
47 XXY; meiotic nondisjunction.
What is the karyotype of Turner syndrome?
What is a true hermaphordite?
Presence of both ovarian and testicular tissue within an individual.
What are Mendelian disorders?
Disorders characterized by single gene mutation.
What are point mutations?
Single nucleotide base substitution.
What are synonymous mutations?
AKA silent mutations: a base substitution resulting in a codon that codes for the same amino acid.
What is a Missense mutaiton?
A base substitution resulting in a new codon and a change in amino acids.
What is a nonsense mutation?
A base substitution producing a stop codon and therefore producing a truncated protein.
What is a frameshift mutation?
Insertion or deletion of bases leading to a shift in the reading frame of the DNA.
What is Cystic fibrosis?
AKA Mucoviscidosis, mutation of the chloride channel protein , cystic fibrosis transmembrane conductance regulator (CFTR), leads to abnormally thick viscous mucous, which obstructs the ducts of exocrine organs.
Where is the CFTR gene located?
What enzyme converts phenylalanine into tyrosine?
What causes phenylketonuria (PKU)?
Deficiency of phenylalanine hydroxylase, resulting in toxic levels of phenylalanine.
What causes alkaptonuria (ochronosis)?
Deficiency of homogentisic oxidase resulting in the acumulation of homogentisic acid. Homogentisic acid has an affinity for connective tissue (especially cartilage) resulting in a black discoloration (ochronosis).
What is Type I glycogen storage disease and what are its symptoms?
von Gierke disease; caused by the deficiency of glucose-6-phosphate. Causes hepatomegaly and hypoglycemia.
What is Type II glycogen storage disease and what are its symptoms?
Pompe disease; caused by deficiency of Lysosomal glucosidase (acid maltase). Causes hepatomegaly, skeletal muscle hypotonia, cardiomegaly, and death from cardiac failure by age two.
What is Type IV glycogen storage disease and what are its symptoms?
McArdle syndrome; caused by deficiency of muscle phosphorylase. Causes exercise-induced muscle cramps.
What causes Tay-Sachs disease?
A type pf lysosomal storage disease, it is caused b a deficiency of hexosaminidase A; leads to the accumulation of GM2 ganglioside in the lysosomes of the CNS and retina.
What are the symptoms of Cystic Fibrosis?
I. Lungs: Recurrent pulmonary infection, chronic bronchitis, bronchiectasis. II. Pancreas: Insufficiency, fat malabsorption, deficiency of fat-soluble vitamins. III. Male reproductive system: Obstruction of vas deferens and epididymis - may lead to infertility. IV. Liver: Plugging of the biliary canaliculi may result in biliary cirrhosis. V. GI tract: samll intestinal obstruction (meconium ileus).
How is Cystic Fibrosis diagnosed?
I. Sweat test (elevated NaCl). II. DNA probes.
What are the symptoms of Phenylketonuria?
I. Normal at birth but profound mental retardation by 6th month. II. Lack of tyrosine: light-colored skin and hair. III. May have a mousy or musty odor to the sweat and urine (secondary to metabilite [phenylacetate] accumulation).
What is the treatment for Phenylketonuria?
Dietary restriction of phenylalanine.
What are the symptoms of Alkaptonuria?
Black urine, black cartilage, discoloration of the nose and ears, early onset of degenerative arthritis.
What is the cause of albanism?
Deficiency of tyrosinase.
What are the symptoms of Tay-Sachs?
Normal at birth, onset by 6th month. Progressive mental deterioration and motor incoordination; death by age 2-3. Common in Ashkenazi Jews.
What is the cause of Niemann-Pick?
A lysosomal storage disease, it is caused by the deficiency of sphingomyelinase, leading to the accumulation of sphingomyelin within the lysosomes of the CNS and reticuloendothelial system.
What are the symptoms of Niemman-Pick?
Normal at birth, onset by 6th month. Progressive mental deterioration and motor incoordination; death by age 2. Common in Ashkenazi Jews. Massive splenomegaly and lymphadenopathy. Cherry-red spot on retina, distended neurons with foamy cytoplasmic vacuolization. There may be bone marrow involvement.
What are zebra bodies?
Distended lysosomes containing lamellated figures, seen in Niemman-Pick.
What causes Gaucher disease?
A lysosomal storage disease, it is caused by the deficiency of glucocerebrosidase, leading to the accumulation of glucocerebroside predminately in the lysosomes of the reticuloendothelial system.
What are the symptoms of Gaucher disease?
Type I is 99% of cases and presents in adulthood. Hepatosplenomegaly, hypersplenism that leads to thrombocytopenia/pancytopenia, lymphadenopathy, bone marrow involvement that may lead to bone pain, deformities, and fractures.
Which type of Gaucher disease affects CNS?
Types II and III.
What are Gaucher's cells?
Enlarged macrophages with a fibrillary (tissue-paper-like) cytoplasm.
What causes Mucopolysaccharidosis (MPS)?
Group of lysosomal storage disorders characterized by deficiencies in the lysosomal enzymes requied for the degredation of mucopolysaccharides (glycosaminoglycans).
What are symptoms of Mucopolysaccharidosis?
I. Mental retardation. II. Cloudy cornea. III. Hepatosplenomegaly. IV. Skeletal deformities and coarse facial features. V. Joint abnormalities. VI. Cardiac lesions.
What is Mucopolysaccharidosis (MPS) type I and what causes it?
AKA Hurler syndrome, it is the severe form of MPS, caused by the deficiency of alpha-1-Iduronidase, leading to an accumulation of dermatan sulfate and heparin sulfate.
What is Mucopolysaccharidosis (MPS) type II and what causes it?
AKA Hunter syndrome, it is the mild form of MPS and is the one linked to chromosome X, caused by the deficiency of L-iduronosulfate sulfatase, leading to an accumulation of dermatan sulfate and heparin sulfate.
Which lysosomal storage disease is the most common?
What is the cause of Familial hypercholesterolemia?
An autosomal storage disease, it is caused by low density lipoprotein (LDL) receptor gene on chromosome 19.
What is the specific cause of Class I Familial hypercholesterolemia?
No LDL receptor synthesis.
What is the specific cause of Class II Familial hypercholesterolemia?
Defect in transportation out of the endoplasmic reticulum.
What is the specific cause of Class III Familial hypercholesterolemia?
Defect in LDL receptor binding.
What is the specific cause of Class IV Familial hypercholesterolemia?
Defect in ability to internalize bound LDL.
What is the specific cause of Class V Familial hypercholesterolemia?
Defect in the recycling of the LDL receptor.
What are the elevation levels of serum cholesterol in heterozygotes with familial hypercholesterolemia compared to normal people?
2 to 3 times normal level.
What are the elevation levels of serum cholesterol in homozygotes with familial hypercholesterolemia compared to normal people?
5 to 6 times normal level.
What are skin xanthomas?
Collections of lipid-laden macrophages.
What is the cause of Marfan syndrome?
Mutation of the fibrillin gene (FBN1) on chromosome 15q21. Fribrillin is a glycoprotein that functions as a scaffold for the ligament of elasic fibers.
What are the symptos of Marfan syndrome?
Tall, thin build with long extremeties, hypersensible joints, pectus excavatum, pectus carinatum, bilateral subluxation of the lens (ectopia lentis), cystic medial necrosis that leads to dissecting aortic aneurism, dilation of the aortic ring, and mitral valve prolapse.
What is Ehlers-Danlos syndrome (EDS)?
A group of inherited connective tissue disease that have in common a defect in collagen structure or synthesis.
What are the clinical symptoms of Ehlers-Danlos syndrome?
Hyperextensible skin, which is easily traumatized and hyperextensible joints.
What is the cause of Ehlers-Danlos syndrome (EDS) type 4?
Autosomal Dominant, defect in type III collagen.
What is the cause of Ehlers-Danlos syndrome (EDS) type 6?
Autosomal Recessive, it is in a defect in lysyl hydroxylase (enzyme responsible for hydroxylation of lysine residues [a recessive disease]).
What is the cause of Ehlers-Danlos syndrome (EDS) type 9?
X-linked recessive, it is caused by a defect in copper metabolism.
In which type of Ehlers-Danlos do we see diaphragmatic hernias?
EDS type 1.
In which type of Ehlers-Danlos do we see retinal detachment and kyphoscoliosis?
EDS type 6.
In which type of Ehlers-Danlos do we see arterial or colonic rupture?
EDS type 4.
Which type of Neurofibromatosis is the most common?
Type I (von Recklinghausen diease). Accounts for 90% of neurofibromatosis.
What is Type I neurofibromatosis and what gene is responsible?
Tumor suppressor gene: NF-1, chromosome 17 (17q11.2). Normal gene product (neurofibromin) inhibits p21 ras oncoprotein.
What are the symptoms of Type I neurofibromastosis?
Type 1: von Recklinghausem (17 letters for chrosome 17): Multiple neurofibromas, Pigmented skin lesions (cafe-au-lait spots), pigmented iris hamartomas (Lisch nodule), increased risk of meningiomas and pheochromocytoma.
What is Type II neurofibromatosis and what gene is responsible?
Type II: bilateral acoustic neurofibromatosis. Tumor suppressor gene: NF-2, Chromosome 22, normal gene product (merlin) has unknow function.
What are the symptoms of Type II neurofibromastosis?
Bilateral acoustic neuromas, neurofibromas and cafe-au-lait spots, increased risk of meningiomas and ependymomas.
What is von Hippel-Lindau disease?
AD disease by a tumor suppressor gene in chromosome 3, it causes retinal hemangioblastoma (von Hippel tumor), hemangioblastoma of cerebellum, brain stem, and spinal cord (Lindau tumor), cysts of the liver, pancreas, and kidneys, and mutiple bilateral renal cell carcinomas.
What is fragile X syndrome?
The second most common cause of familial mental retardation, caused by trinucleotide repeat of CGG in the X chromosome (Xq27.3). Causes mental retardation, elongated face with a large jaw, large everted ears, macro-orchidism.
What is Huntington's disease?
Trinucleotide repeat expansion of (CAG) of the huntington gene produces an abnormal protein (Huntington), which is neurotoxic. Causes atrophy of caudate nucleus, pregressive dementia and choreiform movements.
What is genomic imprinting?
Differential expression of genes based on chromosomal inheritance from maternal versus paternal origin.
What is Prader-Willi syndrome?
An example of genomic imprinting, cuased by the deletion on paternal chromosome 15 [del(15)(q11;q13)]. Causes mental retardation, obesity, hypogonadism, and hypotonia.
What is Angelman syndrome?
AKA happy puppet syndrome, another example of genomic imprinting, caused by the deletion on maternal chromosome 15 15[del(15)q11;q13)]. Causes mental retardation, seizures, ataxia, inappropriate laughter.