Genetics (stein)- Diseases in general

Question 1

Albinism- mechanism of disease, Sx

Answer 1

Mutation in tyrosine oxidase. No pigment in skin or eyes (red irises)

Question 2

Phenylketonuria- mechanism, things you would detect on labs, Tx

Answer 2

Mutation in phenylalanine hydroxylase. Build up of Phe in blood and phenylpyruvic acid in urine. Restricted diet.

Question 3

Non-PKU hyperphenylalaninemia- how does it differ from PKU?

Answer 3

Less severe. May not need restricted diet as Tx

Question 4

Variant PKU- how does it differ from PKU?

Answer 4

Severity is less than PKU, greater than that of non-PKU hyperphenylalaninemia. Requires somewhat restrictive diet

Question 5

BH4 metabolic deficiency- clinical signs, Tx

Answer 5

Hyperphenylalaninemia (example of locus heterogeneity). Supplement with oral BH4 and NT precursors (i.e. L-dopa and OH-trp)

Question 6

Tay Sachs disease- mech of inheritance, mechanism of disease, clinical presentation, Tx

Answer 6

autosomal recessive. Mutation in hexosaminidase A leads to build up of GM2 gangliosides in lysosomes. Pt regresses in devel milestones beginning at 3-6 mo, dies by 2-4 yrs. Common in Ashkenazi Jewish pop. No Tx.

Question 7

Osteogenesis Imperfecta- mech of disease, mech of inheritance, Sx

Answer 7

Mutations in type 1 collagen. Autosomal dominant. Brittle bones, skeletal deformities.

Question 8

Ehler-danlos syndrome- mech of disease, Sx

Answer 8

Error in post-translational collagen modification. Fragile skin, hyper mobile joints, hyper extensible skin

Question 9

Marfan syndrome- mech of disease, Sx

Answer 9

Mutation in fibrillin gene (assoc with elastin). Tall, thin pt with long, thin fingers. Possible pneumothorax, dislocation of lens, aortic dilatation and dissection

Question 10

Down syndrome- karyotype appearance, Sx,

Answer 10

Trisomy 21. Mental retardation, short stature, characteristic flat face with protruding tongue, usually infertile (but if reproduce, don’t usually transmit extra chrome 21)

Question 11

Patau syndrome- karyotype, Sx

Answer 11

Trisomy 13. Failure to thrive, bilateral cleft lip and palate, rocker-bottom feet with a prominent heel, polydactyly, “punched-out” scalp (bald spot)

Question 12

Edwards syndrome- karyotype, Sx

Answer 12

Trisomy 18. Receding chin and sloping forehead, hypotonia, hand sign (thumb crossed over palm with 1st 3 fingers over thumb and pinky across the 3 fingers). Pts often die within the first month of life

Question 13

XXX female- Sx

Answer 13

Seems normal. May be tall. May have learning deficits and/or fertility problems

Question 14

XYY male- Sx

Answer 14

May be tall. Normal intelligence and fertility. Clinically indistinguishable from 46XY male

Question 15

Klinefelter syndrome- karyotype, Sx

Answer 15

XXY. Tall, infertile, possible learning deficits, female characteristics (breast development, extra fat on hips)

Question 16

Turner Syndrome- karyotype, Sx, Tx

Answer 16

45X. Short, webbed neck (from edema in utero), short hands and fingers, infertility likely. Growth horome and possible surgical removal of gonads if pt is 45X/46XY mosaic with female phenotype (risk of gonadoblastoma)

Question 17

XY female- mechanism of disease, Sx

Answer 17

Defect in androgen receptor gene. No Mullerian duct or Wolffian duct development. Normal female external genitalia with testes in abdomen. Infertile

Question 18

21-a-hydroxylase deficiency- karyotype, mech of disease

Answer 18

XX male. Autosomal recessive. Mom or child has deficiency causing overproduction of androgens-> virilization of female fetus. Ovaries and internal genitalia are normal but external genitalia are ambiguous

Question 19

XX male- mech of disease

Answer 19

XY recombination near pseudoautosomal region. SRY moved to X chromosome (unbalanced translocation). Male is usually normal. His children could have a Klinefelter phenotype if male and a Turner phenotype if female.

Question 20

Wolff-Hirschorn syndrome- mechanism of disease, Sx

Answer 20

4p deletion. Greek warrior’s helmet face (surprised expression, arched brows, long nose with squared off end), short stature, developmental delay

Question 21

Williams Syndrome- mech of disease, Sx

Answer 21

7q deletion, including elastin gene. Supravalvular aortic stenosis, thickening of skin, coarse hair, skeletal and joint limitations. Low IQ but excellent musical skills. Very outgoing and friendly. Blue sclera and stellate iris.

Question 22

Velocardiofacial syndrome- mech of disease, Sx

Answer 22

3 MB del on chrom 22 (long arm), possibly due to unequal crossing over. May be inherited. Learning disabilities, hypotonia at birth, short stature, typical facial anomalies, cardiac anomalies, feeding difficulty at birth

Question 23

Prader-Willi syndrome- mech of disease, Sx

Answer 23

15q del on paternal chromosome or maternal disomy of 15 or imprinting error so it seems like pt has 2 maternal chrom 15s. Hypotonia at birth, obesity later in life, small hands and fed, hypogonadism, “devilish,” devel delay

Question 24

Angelman syndrome- mech of disease, Sx

Answer 24

15q del on maternal chromosome or paternal disomy of 15 or imprinting error so it seems like pt has 2 paternal chrom 15s or UBE3A mutation. Severe mental retardation, friendly, hyperactive, short, ataxic

Question 25

Rett syndrome- mech of disease, Sx

Answer 25

Mutation in MECP2 on X chromosome. Typically in females. Normal development arrests, then regresses. Problems controlling hands and feet, intellectual disability, loss of speech, seizures. Phenotype is variable due to X-inactivation

Question 26

MERRF (myoclonic epilepsy with ragged red fiber disease)- mech of inheritance, some symptoms

Answer 26

``` Mitochondrial inheritance (many different phenotypes seen) Seizures, hearing loss, ataxia, unsteadiness, dementia/cognitive delay ```

Question 27

Chronic myelogenous leukemia (CML): mech of disease, type of gene product,

Answer 27

translocation of chromosomes 9 and 22 (unbalanced), chimeric oncogene (bcr-abl, gain of function of abl tyrosine kinase)

Question 28

Acute promyelocytic leukemia (APL): mech of disease, diagnosis of disease

Answer 28

t(15;17) involving a proto-oncogene (PML). Detection of translocated chromosome is Dx of the disease

Question 29

Retinoblastoma: Sx, mech of disease, age of onset

Answer 29

Tumor in the eye. Can grow forward or backwards (into the brain, lethal). Mutation in Rb1 gene (tumor suppressor) on chrom 13 0-5 yrs- when pt has retinoblasts still and no retinal cells yet

Question 30

Li fraumeni syndrome: pedigree description, mech of disease

Answer 30

Familial cancer syndrome (no one specific type), p53 (tumor suppressor) mutation

Question 31

Breast cancer- mech of disease in familial form

Answer 31

Mut in BRCA1 or BRCA2 genes (involved in DNA repair) in addition to other mutations

Question 32

Chromosomal breakage syndromes (i.e. fanconi anemia, bloom syndrome, ataxia telangiectasia, xeroderma pigmentosa, cockayne syndrome): mech of inheritance, mech of disease, Sx, karyotype appearance

Answer 32

Autosomal recessive Mutations in DNA repair genes (i.e. DNA ligase 1 or helicase in Bloom syndrome; excision repair genes in Xeroderma pigmentosa and cockayne syndrome) Increased susceptibility to cancer Multiple sister chromatid exchanges, triradial chromosomes, excessive breakage or gapping in chromosomes

Question 33

Hereditary non polyposis colon cancer: mech of disease, genetic aspect of Dx

Answer 33

Mutation in a DNA mismatch repair gene (tumor supressor gene). 1 mutated copy inherited-> 70-90% chance pt will develop colon cancer in lifetime Microsatellite analysis used to confirm clinical Dx (multiple bands present due to amplification or deletion of repeat regions)

Question 34

Acute myelocytic leukemia (AML-M4): chromosomal finding diagnostic for disease

Answer 34

inversion of chromosome 16

Question 35

Gaucher disease: mech of disease, Tx

Answer 35

Deficiency of glucocerebrosidase lysosomal enzyme. Glucocerebrosides build up in lysosomes. Replacement therapy for the enzyme (targeted so macrophages pick it up from the bloodstream)