Genetics Flashcards
Mode of inheritance of Duchenne’s muscular dystrophy and what is it
Duchenne’s muscular dystrophy predominantly affects males; it is an X-linked Recessive Disease
-due to frameshift (deletions, duplications, or nonsense) mutations truncated dystrophin protein inhibited muscle regeneration. Weakness begins in pelvic girdle muscles and progresses superiorly. Pseudohypertrophy of calf
muscles due to fibrofatty replacement of muscle A . Gower maneuver—patients use upper extremities to help them stand
Dx lab: elevated CK and aldolase
All lysosomal storage diseases are ____ except these two which are
all are Autosomal Recessive except Hunter and Fabry which are X-linked Recessive
Four examples of trinucleotide repeat disorders are:
- Fragile X (CGG repeats in the FMR1 gene on the X chromosome.) X-linked dominant inheritance
- Huntington disease ( >35 CAG repeats on chromosome 4) Huntington disease is autosomal dominant. Symptoms develop at20 to 50 years of age.
- Friedreich’s ataxia (expanded trinucleotide (GAA) repeat within the gene that encodes frataxin on chromosome 9). Autosomal recessive
- Myotonic dystrophy (>50 CTG repeats of the gene for myotonic dystrophy protein kinase (DMPK gene) on chromosome 19. Autosomal dominant
types of collagen and where they are found
Type I: Bone, tendon, skin, fascia, late scar tissue, cornea. Type I is the most common type of collagen in the body (~90%). “Type ONE → bONE”
Type II: Cartilage, vitreous humor, nucleus pulposus. “Type TWO → carTWOlage”
Type III: Reticular fibers in skin, blood vessels, fetal tissue, uterus, and granulation tissue. “Type THREE → ReTHREEculate fibers”
Type IV: Basement membrane, lens of the eye, and basal lamina. “Type FOUR is found under the FLOOR (basement membrane)
phases of cell cycle and way to remember
Go Sally Go! Make Children!
Patients with Down Syndrome are likely to have these specific defects
- cardiac
- Upper GI
- Lower GI
- Neuro
- Leukemia
- cardiac: AV septal defect (a form of endocardial cushion defect), VSD, ASD
- Upper GI: duodenal atresia
- Lower GI: Hirschsprung disease and imperforate anus (both have failure to pass menconium)
- Alzheimer (virtually 100% in 40’s)
- Leukemia: ALL (acute lymphoblastic leukemia) and AML (acute myeloid leukemia)
kwashiorkor presentation
The typical presentation of kwashiorkor is a child with a swollen belly due to ascites (accumulation of fluid in the peritoneal cavity) and an enlarged, fatty liver. Patients may also have normal or near normal height and weight, anasarca, pitting edema of the lower extremities, dry, atrophic, peeling skin, dry hair that falls out easily, and dilated intestinal loops.
X-linked Recessive Disorders
Bob’s Father Has GOLD Wagon
B- brutton’s agammaglobulinemia
F - fabry’s
H - hunter’s/ hemophilia A and B
G - G6PD deficiency
O - ocular albinism
L - lesch-nyhan
D - duchenne’s muscular dystrophy
W- wiskott-aldrich
Cri-du-chat syndrome
Congenital microdeletion of short arm of chromosome 5 (46,XX or XY, 5p−).
Findings: microcephaly, moderate to severe intellectual disability, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities (VSD).
Severe Combined Immunodeficiency (SCID)
Defective cell mediated and humoral immunity
3 main etiologies
- Defective IL-2 gamma chain (X-linked)
- Adenosine Deaminase deficiency (AD is AR)
- MHC Class II deficiency (necessary for CD4 helper T cell activation and cytokine production
Recurrent viral, bacterial, fungal, protozoal infections
If need to give them blood transfusion, better make it IRRADIATED BLOOD because they have no immune system to fight anything introduced
Absence of Thymic Shadow, no germinal centers in follicles of lymph nodes
X-linked (Bruton) agammaglobulinemia
Defect in BTK, a tyrosine kinase gene no B-cell maturation. X-linked recessive ( in Boys).
-complete lack of immunoglobulin due to disordered B cell maturation
Presents after 6 months of life (mother protection) with bacterial (no Ab), enterovirus, Giardia (no IgA)
*also see NO TONSILS*
Hyper IgM syndrome
Due to mutated CD40L or CD40 receptor.
- the second signal cannot be delivered to helper T cells during B-cell activation.
- cytokines IL-4 and IL-5 necessary for class switching cannot be produced.
LOW IgA, IgG and IgE and associated infections
anergy
State during which a cell cannot become activated by exposure to its antigen. T and B cells become anergic when exposed to their antigen without costimulatory signal (signal 2). Another mechanism of self-tolerance.
Regulatory T cells
Help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions. Identified by expression of CD3, CD4, CD25, and FOXP3.
-Activated regulatory T cells produce anti-in ammatory cytokines (e.g., IL-10, TGF-β).
Edwards syndrome (trisomy 18), 1:8000
severe intellectual disability, rocker- bottom feet, micrognathia (small jaw), low-set Ears, clenched hands with overlapping fingers, prominent occiput, congenital heart disease. Death usually occurs within 1 year of birth
-Election age (18).
