Genetic Disorders
a single gene variant that alters protein or decreases protein/enzyme productions
what is single-gene disorder?
one copy of a gene causes disease. it's a mutation of extracellular matrix protein abundant in connective tissue. Clinical manifestations include skeletal abnormalities (long arms & fingers + hyper-extensible joints), vision problems, and cardiovascular complications (floppy valves)
what is Marfan Syndrome ?
contain DNA that is distant from DNA in nucleus
what is mitochondria DNA (mtDNA)?
homozygous (both Xs have trait) to show phenotype. If heterozygous for trait, will RARELY have phenotype
what are XX persons with recessive disorders ?
structural abnormalities where chromosome breaks into pieces then rearranges of parts are deleted.
what is chromosomal disorder?
Tay-Sachs, Cystic Fibrosis, & Sickle Cell Anemia
genetic defect in tumor suppressor gene and causes tumors to develop in the nervous system. There are 2 types: von Recklinghausen disease (in peripheral nerves) & bilteral acoustic (Shwann cell tumors; less common; symptoms headache, hearing loss, tinnitus)
what is neurofibromatosis?
these disorders are not common and often cuase problems in tissues with high metabolic needs (i.e. muscle & nervous)
what are mitochondrial DNA disorders (mtDNA) disorders?
Only has one X chromosome, so all XY people affected. Also occurs in X0 persons
what is numeric autosomal chromosomal disorder?
cutaneous + subcutaneous neurofibromas that develop late in childhood or adolescence as well as cafe au lait spots (large, flat pigmentations)
what are clinical manifestations of Neurofibromatosis?
Diabetes, cardiovascular disease, cancer.
what are disorders that manifest due to environmental influences?
XX offspring have 50% chance of being carrier. XY offspring has 50% chance of having disease. An affected XY person will give X gene to ALL XX offspring.
what is parent is a XX carrier?
Error in meiotic cell division. This is the most common chromosomal disorder. Manifestations include: intellectual disability, physical characteristics, & congenital heart defects. Increased risk of lymphoblastic leukemia & GI malformations.
what is Trisomy 21/Down Syndrome?
metabolic disorder where elevated phenylalanine levels are toxic to the brain. Deficiency in liver enzyme (PAH) that converts phenylalanine to tyrosine. Source is protein rich foods and we only use a little and convert the rest. Fasting, starvation triggers muscle catabolism = increased levels. This is screened in birth and if left untreated = will cause intellectual impairment & impaired neurologic development
mutant X* chromosome is dominant to normal X. Will be affected. Affected heterozygous persons (X*X) has a 50 % chance to transmit the mutant X* chromosome to offspring. X*Y persons will have 100% affected XX offspring (all will be affected) and 100% unaffected X*Y offspring (if other parent doesn't have mutated X chromosome).
what is X-linked dominant disorders?
Absence if all (45 chromosomes, X0) or part of X chromosome. Clinical features include: short stature, ovarian dysgenesis, cardiac abnormalities. Can be treated with growth hormone and estrogen therapy.
what is Turner Syndrome?
Lysosomal storage disorder due to lack of hydrolytic enzyme leading to increases sphingolipids in nervous tissue (brain). This leads to destruction of neurons which leads to gradual deterioration of motor & mental function. This is fatal at 4-5 years of age.
what is Tay-Sachs?
This is the most common form of inherited intellectual disability X-linked dominant disorder. Affected males (X*Y) are more severe than affected females (X*X)
what is Fragile X syndrome?