Bold is Beautiful, exam 1 Flashcards
(81 cards)
1
Q
cystic fibrosis
A
- multisystem disease
- affecting digestive system, pulmonary, sweat glands and reproductive tract
2
Q
major cause of morbidity and mortality in CF
A
-the progression of lung disease
3
Q
the CF mutation
A
- single large gene on chromosome 7
- cystic fibrosis transmembrane conductance regulator (CFTR) protein
4
Q
CFTR protein
A
-regulates volumes and composition of exocrine secretion
5
Q
CF gene type
A
- autosomal recessive exocrinopathy, affects multiple epithelial tissues
- one recessive allele from father and mother “ee”
6
Q
how many CFTR genes with potential to cause disease
A
1900 different mutations
7
Q
most common mutation in CF
A
- delta F508
- deletion of three DNA bases
- 70% of Caucasian patients
- founder effects: certain mutations are found at higher frequency
8
Q
CFTR gene classification
A
- 5 different classes
- class I to III cause more severe disease (tRNA/mRNA involvement)
9
Q
CF class I mutations:
A
- defective protein production
- cause by nonsense, frameshift, splice-site mutation
- leads to premature termination of the mRNA
- complete absence of the CFTR protein
- 60% of Ashkenazi jews carry the nonsense mutation (founder effect)
10
Q
CF class II mutation:
A
- defective protein processing
- prevents the protein from trafficking to the correct cellular location
- delta F508
- 70% of disease causing alleles in the U.S.
- 50% are homozygous for F508 deletion
- 90% will carry at least one copy of this mutation
11
Q
CF class III mutation:
A
-diminished channel active in response to ATP
12
Q
CF class IV mutation:
A
- protein is produced correctly and on cell surface
- the rate of ion flow and the duration of channel opening are reduced compared to normal CFTR function
- known as gating defect
13
Q
CF class V mutation:
A
- reduced amounts of functional CFTR protein
- alter the stability of the mature CFTR protein
14
Q
CF gene modifiers
A
- inconsistent association between CF genotypes and phenotypes
- not directly related to the CFTR gene but affects the severity of clinical manifestations
- 20% of patients exacerbates the pulmonary disease
15
Q
CFTR gene classifications
A
- combination of mutations are often unclear
- due to the influence of gene modifiers
- specific mutations should not be used to make assumptions
- truly variable
16
Q
Mannose-binding lectin (MBL)
A
- important in the complement system
- increased risk for pyogenic infections
- reduced lung function
- burkholderia cepacia complex
- early death
17
Q
TGF-beta 1 in CF
A
- transforming growth factor-beta
- suppressor of T cell activation
- associated with more severe CF lung disease
18
Q
CF time course
A
- highly variable time course from months to decades
- develop chronic infections of the respiratory tract
19
Q
CF: incomplete phenotype
A
-10% of patients have unusually mild manifestations or limited to one organ
20
Q
immunoreactive trypsinogen test (IRT)
A
- chemical made by the pancreas
- when a pancreas is stressed before a baby is born, more IRT is released into the baby’s blood
- higher for a premature or stressful delivery
21
Q
chloride sweat test
A
- stimulate localized sweating
- uses chemical pilocarpine
- collected on Gibson-cooke (gauze)
- > 60 mmol/L indicative of cystic fibrosis
- demonstrates clinical disease in one or more organs
- 20% of children with intermediate sweat chloride results will have DNA evidence of CF on expanded analysis
22
Q
non-classic CF
A
- 2% of patients
- full diagnostic criteria but have normal/intermediate sweat chloride result
- who were diagnosed as adults
- lower frequency of delta F508 mutations
23
Q
survival for CF
A
-median: 36.8 years
24
Q
CF presenting symptom and signs
A
- persistent pulmonary infection
- pancreatic insufficiency
- elevated sweat chloride levels
25
CF respiratory flora
- complex bacterial flora that includes staphylococcus aureus, haemophilus influenza and pseudomonas aeruginosa
- burkholderia cepacia: less favorable pulmonary outlook
26
CF pancreatic secretions
- tenacious exocrine secretions obstruct pancreatic ducts and impair production and flow of digestive enzymes to the duodenum
- loss of pancreatic islet cell mass
- CF-related diabetes mellitus in over 30% of adults
27
CF hepatic
- obstruction of intrahepatic bile ducts
| - multilobular cirrhosis in 4-15% of patients
28
intestinal CF
- 10-20% of newborns with CF
| - contents of intestinal lumen are difficult to excrete
29
CF presentation in infants and children
- meconium ileus: 2 weeks in diagnosing
| - other symptoms: 14.5 months diagnosing
30
reproductive CF
- represent a developmental abnormality secondary to secretory obstruction of the vas
- nearly half of all men with congenital bilateral absence of the vas deferens and normal lung function have two CFTR mutations
31
CFTR-related metabolic syndrome (CRMS)
- asymptomatic infants with equivocal (ambiguous) results
| - sweat chloride tests may change with age
32
DNA testing with CF
- intermediate results of sweat testing should be clarified by DNA analysis using a CFTR multimutation method
- most labs in the U.S. screen for 23 of the common mutations
- California has a panel of 40 mutations
- 2 CF-causing mutations are detected, sweat test is intermediate/positive, diagnosis is confirmed
- nasal potential difference measurements
33
CF pathogens
- pseudomonas aeruginosa
- airway particularly susceptible to pseudo. aeruginosa within the first year of life
- staphylococcus aureus- in respiratory secretions of CF infants and children
- burkholderia cepacia complex- accelerated decline in pulmonary function and shortened durvival
- B. cenocepacia is contraindication to transplant
34
mRNA
- transcription
- nucleus to cytoplasm to manufacture proteins (translocation)
- determines the phenotype
35
chromosomes
- by which genes are transmitted from generation to generation
- humans have 46 chromosomes is 23 pairs
- one pair is the sex pair, XX, XY
- autosomes: other 22 pairs
- mitochondria contain multiple copies of a small chromosome
36
mitochondria chromosomes
- encodes a few proteins for oxidative metabolism
| - all of the transfer ribonucleic acids (tRNA) used in translation of proteins in the organelle
37
locus
-exact location of a gene on a chromosome
38
alleles
- homologous copies of a gene (similar but not identical)
| - each carries the same genes in the same order but the alleles for each trait may not be the same
39
homozygous
-pair of matching alleles
40
heterozygous
-a pair of genes where one is dominate and one is recessive
41
alkaptonuria (AKU)
- rare disease
| - causes severe, early onset osteoarthritis
42
mutation
-and change in DNA that may adversely affect the host
43
germinal mutations
- caused by radiation/chemical mutagens
- may affect a single gene or an entire chromosome
- affects the progeny(descendants) where the mutation arose
44
somatic mutation
-genetic alteration acquires by a cell that can be passed to the progeny of the mutated cell in the course of cell division
45
chromosomal aberrations
- morphological: mutations that affect the appearance or shape of an organism's parts
lethal: results in death of an organism
46
impact of genetic disease
- spontaneous miscarriages: 40-50% of all recognized first-trimester pregnancy losses have a chromosomal anomaly
- >50% of adults will be affected by something that is genetically determined
- response of treatment is also likely affected by genes
47
heterozygous reciprocal translocation
-which two non-homologous chromosomes have interchanged terminal segments
48
homozygous reciprocal translocation
-on homozygous translocation both pairs interchange
49
aneuploidy
-condition where extra or fewer copies of a particular genes or chromosomal regions are present
50
monosomy
-one member of a pair of chromosomes is missing from a diploid pair
51
trisomy
-one extra chromosome is present with the diploid pair
52
polysomy
-more than 3 copies of a chromosome are present
53
polygenic
-most human diseases results from a combined action of alleles of more than one gene
54
monogenic
-disease/condition that results from the action of alleles at one gene
55
"mendelian"
- phenotypes due to alterations at a single gene
| - showed some traits were dominant relative to other traits
56
autosomal dominant inheritance
- males and females equally affected
| - only one parent must be affected for an offspring to be at risk for developing the phenotype
57
autosomal recessive inheritance
-matings between individuals with the same recessive phenotype, all offspring will be affected
58
sex linked traits
-X-linked traits more prominent
59
neurofibromatosis 1
- heterozygous mutation
- chromosome 17q11
- autosomal dominant
- peripheral neurofibromatosis
- most common type
- normal life expectancy
60
neurofibromatosis 2
- mutation in the gene encoding merlin
- chromosome 22q12
- central neurofibromatosis
- rare, affects 1 in 25,000
- 50% of affected people inherit the disorder
61
NF 1 phenotype
- café-au-lait spots
- lisch nodules in the eye
- fibromatous tumors of the skin
- freckling arm pits or groin
- dystrophic scoliosis: less common
62
NF 2 phenotype
- hallmark finding: presence of slow-growing tumors on the eight cranial nerve
- acoustic branch: hearing
- vestibular: balance
- vestibular schwannomas
63
NF 2 criteria
- tumor on the optic nerve or
- abnormal development of the spine, temple bone of skull or tibia
- a parent/sibling/child with NF 2
- bilateral vestibular scbwannomas
64
NF 2 early symptoms
- 18 and 22 years of age
- most frequent: hearing loss or ringing in the ears (tinnitus)
- less often: disturbances in balance, visual impairment (cataracts)
65
NF treatment
- surgery (tumor size and impairment)
- radiation
- chemotherapy
- NF1: controlling or relieving symptoms
66
NF 2 outcome
- varies greatly among individuals
| - an earlier age of onset and the presence of meningiomas are associated with greater mortality risk
67
downs syndrome
- meiotic nondisjunction
- 88% coming from nondisjunction in the maternal gamete
- varies greatly from individual to individual
68
downs syndrome translocation
- translocation keryotype (14/21 there is an extra copy of the 21 chromosome on the short arm of 14- robertsonian)
- familial down syndrome
- not distinguishable clinically
69
down syndrome marker
- the same biochemical marker used for detecting trisomy 18, Edwards syndrome
- 2nd most common autosomal trisomy among live births
70
downs syndrome screening
- approach should be nondirective
- risk-benefit conversation
- raising a child with a chromosomal abnormality vs termination
- patient needs to decide
- before 20 weeks of gestation
- assessment of maternal serum levels or specific ultrasound markers (most used) 11-13 weeks
- Materni21- blood test (cell-free fetal DNA screening)
71
downs syndrome quadruple test
- second trimester
- 15 to 18 weeks but late as 22 weeks
- measures 4 biochemical markers: alpha-fetoprotein (AFP), unconjugated estriol, human chorionic gonadotropin (hCG) and inhibin A
72
down syndrome findings
-head and neck: flat facial profile/nasal bridge, small ears, brachycephaly, protruding tongue, short neck, brushfield spots
73
DS cognitive deficits
- primarily in morphosyntax, verbal short term and explicit long term memory
- syntax: average sentence length and structure
- language comprehension is equal to mental age
74
DS internal issues
- complete AV canal:37%
- VSD: 31%
- ASD: 15%
- duodenal atresia: 5%
- tracheoesophageal fistula/ esophageal atresia
- Hirschsprung disease: lack of movement in part of bowel
- celiac disease
- refractive errors: 35-76%
- diabetes
75
DS atlantoaxial instability
- excessive mobility of the atlas (C1) and axis (C2), may lead to subluxation
- 13% have asymptomatic AAI
- important ER evaluation
76
Huntington's disease
- autosomal dominant disorder
- degeneration of nerve cells
- mutation found on chromosome 4p16
- unstable trinucleotide repeats (36-120)
77
HD presentation
- chorea in adults
| - cerebral cortex cognitive process, memory and perception
78
HD prevalence
- white people of northwestern European ancestry
- most causes are inherited
- sex of parent has strong influence on the expression of HD
- father expresses earlier findings
- onset: 30-50 years
- juvenile onset has faster progression (10-15 years)
- death from extrinsic accident/disease
79
earliest changes in behavior with HD
- irritability
- moodiness
- antisocial behavior
- psychiatric disturbance
- mild dyskinesia
80
chorea
-the incessant, quick, jerky, involuntary movements that are characteristic of HD
81
HD treatment
- symptomatic relief
| - drugs that block dopamine receptors may control dyskinesia
