Diseases Flashcards
Achondroplasia (Mutation)
FGFR3
Gly380Arg -> Gain Of Function
Nonsyndromic Deafness (Mut)
GJB2
Loss of Function
Retinitis Pigmentosum with Deafness
Usher Synd (AR)
Thyroid Goiter with Deafness
Pendred Synd (AR)
Sudden Death, Arrhythmia with Deafness
Jervell & Lange-Nielson Synd (AR)
White Forlock with Deafness
Waardenburg Synd (AD)
8th Nerve Schwannomas with Deafness
Neurofibromitosis Type 8
Nonsyndromic Deafness, congenital
Auto Recessive
Nonsyndromic Deafness, progressive
Auto Dominant
Fragile X Synd
FMR1 Gene, CGG repeat
X-linked, Mild retardation
Alpha 1 - Antitrypsin Therapy
Protein replacement, Replace extracellular protein
Alpha 1 AT is Auto Recessive
Hemophilia therapy
Protein replacement, Factor VIII, Extracellular protein
Gaucher Disease/Fabry Disease Therapy
Target intracellular protein
Pyridoxine-responsive homocystinuria Therapy
Cofactor Administration
Biotinidase Defeciency
Cofactor administration
Enzyme activity (test)
tests for metabolic diseases, Gaucher’s
Biochemical (amino acids) test
tests for PKU
Lipid panel test
familial hypercholesterolemia
X-ray
= Achondroplasia
Sweat Chloride test
= cystic fibrosis
Protein electrophoresis test
sickle cell anemia
Ultrasound test
polycystic kidney disease, hypertropic cardiomyopathy
Klinefelter Synd
47, XXY..
Tall male (long limb with narrow shoulder and chest)
Infertile (hypogonadism, small genetilia)
Learning dificulties, may have poor psychosocial adjustment
XYY Synd
Tall Male, Normal sexual development
Normal inmteligence, Frequent Bahavioral issues
Trisomy
47, XXX
Female, Usually tall. Normal Sex development,
Learning Difficulties
Occasional behavioral issues
Turner Synd
45, XO,
Short Female, Gonadal Dysgenesis, webbed neck, Low posterior hairline, Broad chest with widely spaced nipples, High frequency of cardio and renal issues. Edema of dorsal hands and feet in Newborns.
infertile,
Slightly reduced inteligence
DAX1
Excess of DAX1 (from duplication) can suppress normal male-determining function of SRY, leading to ovarian development.
SOX9
Deletion of SOX9 the testis fail to form. and the ovarian pathway is the default
G6PD Deficiency (Avoid)
Anti-malarial drugs
Acute intermittent porphyria (avoid)
barbiturates
PKU (diet)
reduce phenylanaline
Glactosemia
Reduce glactose
Congenital Hypothyroidism (replacement)
Thyroxine
Biotinidase (replacement
Biotin
Retroviral Gene therapy
Use RNA virus,
ADVANTAGE: integrate into cell genome, Minimal host immune rxn.
DISADVANTAGES: Insert size limited to 7-8kb. Infect only dividing cells. Germ line insertion = BAD
Only one that can be passed to Daughter cells
Adenoviral
DNA virus,
ADVANTAGE: Wide variety of cell types con be infected, Insert size 35-36kb, Stable and easy to get high titers
DISADVANTAGE: Does not integrate into cell genome, Expression can be transient, Some risk of malignant formation. Immune rxn can be severe
Non-viral
Liposome, Direct DNA
ADVANTAGE: Inster size can be very large, Minimal host cell immune response, Could deliver mini-chromosomes.
DISADVANTAGE: Low effeciency, Transient expression
Chromosome Analysis (Good, bad, ugly)
YES: Aneuploidy (Abnormal Chr number), Deletions, Duplications and Insertions of moderate to large size 3500kb-3Mb
NO: Single Nucleotide Deletions. Point Mutation, Small Deletion. Balanced rearangements
USE: Downs Synd,
FISH (good, bad, ugly)
YES: Recognize microdeletion synd, Chromosome rearrangements, Gene copy numbers
NO: Rearangements and deletions that are not specifically tested for, You must know what to look for. POint mutation and small deletions do not work
USE: Cri-du-chat, Smith-Magenis, DiGeorge (22qdel), Williams syndrome, Wolf-Hirschhorn, Prader-Willi syndrome, Angelman syndrome
Microarray Analysis (Good,bad, Ugly) Chromosomal Micro Array
YES: Compare to Control, Look at whole genome. Good for aneuploidy, deletions and duplicaitions, and unbalanced translocations.
NO: Deletions and duplications below the resolution of the CMA,
DNA sequencing (good, bad, ugly)
YES: Mutations in Known genes (Known or novel mutations) small deletions or insertions (specific sequence)
NO: Very specific, only part of a gene. Clinical sensitivity is often below 100%. Not good for large deletions, mutatins, duplications, etc
Paternal Age effect
Achondroplasia, Hemophilia B, Neurofibromitosis
maternal Age effect
Trisomy 21
