retinoblastoma
complicationsstrabismus, lack of red reflex→ leukocoria genetics HirotoShishido
what is the common pathophysiology between CDKN2A, Rb, TP53(gene)code the products which block cell-cycle progression past the G1/S checkpoint
CDKN2A→ melanoma, pancreatic cancer
mutation of chromosome 9q21 is associated with dysplastic nevus syndrome, (nests of nevomelanocytes with ☆hyperchromatic nuclei and bridging with nests in neighboring rete pegs) and patient with this mutation and greater than 3 first degree relatives with melanoma have 75% chance of melanoma in the lifetime geneticsdermatologyUWorld SIM2 HirotoShishido
variable expressivity
examplespatients with the same genotype have varying phenotypes
(⇔pleiotropy= one gene contributes to multiple phenotypic effects eg PKU)
neoplasm associated with BCL-2 overexpressionfollicular and diffuse large B Cell Lymphoma
BCL→antiapoptotic molecule
Bcl-2 keeps the mitochondrial membrane impermeable, thereby preventing ☆cytochrome C release from mitochondria. Bcl-2 overexpression (eg, follicular lymphoma t[14;18])→↓caspase activation→tumorigenesis. geneticshematologyUWorld HirotoShishido
the most common lysosomal strage disease
deficient enzyme, symptomsGaucher disease
glucocerebrosidase
(→treat with recombinant glucocerebrosidase)
☆hepatosplenomegaly, ☆pancytopenia,
+bone lesion(☆avascular necrosis of femur, osteoporosis, bone crisis)
Gaucher cell(lipid-laden cell) can be found throughout the bondy in sites such as liver, bone marrow, and lymphatic tissue biochemistrygeneticsUWorld HirotoShishido
neoplasms associated with overexpression of N-myc and c-MYC respectivelyon the long arm of chromosome 8
(both are ☆transcription factor)
during which of the steps of cell division does cause Down syndrome?95% of Down syndrome is due to anaphase Ⅰ or Ⅱ(分裂後期) nondisjunction
(prophase→metaphase→anaphase→telophase)
4% to Robertsonian translocation
1% to post-infertilization mitotic error(mosaic Down syndrome) genetics HirotoShishido
disease caused by missense mutationsickel cell anemia, ☆MCAD deficiency
usual acidic(negatively chrged) glutamic acid residue is replaced by a nonpolar(neutral charge) valine residue, forming HbS
this leads to the formation of a ☆hydrophobic pocket on the beta globin surface that interacts with a complementary nonpolar residue on another hemoglobin molecule→
this causes polymerization of HbS molecules and subsequent erythrocyte sickling
unilateral Cafe-au-lait spots
polyostotic fibrous dysplasia(多骨性線維性骨異形成症)
→ areas of ☆spindle cells and dysplastic bone most commonly in femur and tibia
(non-inflammatory)
