Biochem and Genetics Flashcards
Describe the important features of Dwarfism; receptor type and genetic inheritance
Fibroblast growth factor receptor 3 FGFR3
AD
How would someone with Laron syndrome respond to GH replacement? IGF-1 replacement? why?
They would not respond to GH replacement because the problem is with the GHR in the liver. This prevents the formation of IGF-1 despite high levels of GH. Thus IGF-1 replacement would help.
AR
A diabetic patient is recently discovered to have laron syndrome but it wasn’t detected for years. What feature of DM may have masked this syndrome?
high insulin levels, b/c insulin can bind to IGF-1 receptors with a low affinity.
What are the clinical features of laron syndrome?
small brain, protruding forehead, acromicria (small fingers and toes)
What is achondroplasia? What is paradoxical about the mutation at the FGFR3?
It means no cartilage growth. Legs are disproportionately short.
FGFR3 signals for production of chondrocytes in the growth plate, and is locked in the on position, but rather than growth, this signal maybe interpreted as cancer and apoptosis likely results.
What is Noonans syndrome and how can it be distinguished from Turner syndrome?
Caused by an AD mutation in the RAS/MAP pathway rather than a chromosomal abnormality as in the cased of Turners (XO).
Noonans aka PTPN or SHP2
PTPN 11-protein tyrosine phosphatase nonreceptor 11
SHP2-Sarc homology phosphatase 2
Dephosphorylates proteins that inhibit RAS therefore increasing its function and increasing cancer risk.
What is aneuploidy mosaicism?
Changes in chromosome number may not necessarily be present in all cells in an individual. When aneuploidy is detected in a fraction of cells in an individual, it is called chromosomal mosaicism. In general, individuals who are mosaic for a chromosomal aneuploidy tend to have a less severe form of the syndrome compared to those with full trisomy
Lyonization inactivates an extra X chromosome leading to barr body formation, but this doesn’t affect the pseudoautosomal region. What is this region and why is it important?
This is the region of homology between the X and Y chromosome and contains genes not inactivated by lyonization such as the SHOX gene=shortness homeobox. This will alter gene dosage in aneuploidy individuals with an extra or deleted X chromosome: Turners XO or kleinfelters XXY leading to short stature or tall stature respectively.
How will deletion of the imprinted region (prader willi) of a maternal chromosome 15 affect someone with a normal paternal chromosome 15?
Deleted an imprinted/inactivated region will have no affect on an individual though it may affect their children.
Prader willi and Angleman have what types of inheritance?
Prader willi maternal chromosome 15
Angleman paternal chromosome 15
