Genetic Disorders Flashcards
What is the genetic basis of phenylketonuria (PKU)?
AR genetic mutation that leads to deficiency of phenylalanine hyroxylase
Causes an accumulation of phenylalanine and a deficiency of tyrosine
What are the physiological symptoms of phenylketonuria (PKU)?
Intellectual disability
Pale skin, fair hair and blue eyes (tyrosine/melanin deficiency)
Microcephaly
Skin rashes and musty odor
What are possible treatment options for phenylketonuria (PKU)?
Dietary supplementation of tyrosine and restriction of phenylalanine ingestion
Novel therapy: PAL injection, converts phe to harmless compounds which can be excreted via urine
Still requires tyrosine dietary supplementation
What is the genetic basis of Hurler Syndrome?
AR genetic mutation that leads to deficient alpha L-iduronidase (IDUA)
Leads to accumulation of heparin and dermatan sulfates
What are the physiological symptoms of Hurler Syndrome?
Dwarfism Kyphosis (hunchback) Intellectual disability Coarse face Reduced joint mobility Clouded corneas
What are possible treatment options for Hurler Syndrome?
Intravenous enzyme replacement therapy
does not cross the brain-barrier so intellectual disability will not be treated
Bone marrow stem cell transplantation
does not reverse pre-transplant complications
What is the genetic basis of neurofibromatosis type I (NF1)?
Heterozygous loss-of-function mutation in NF1 gene which prevents neurofibromin regulation of cAMP pathway and, consequently, cell proliferation
If, by some germline mutation (eg. small deletion), a cell loses its functional NF1 gene and then has no functioning NF1 gene, tumor formation will occur
Individual has one functional NF1, tumor has none (clonal loss)
For diagnosis of NF1, patients have 2 or more of the following characteristics…
6 or more "cafe-au-lait" spots on skin 2 or more neurofibromas optical nerve tumor freckling of armpits and/or groin abnormal development of spine, temple bone of skull, and/or tibia growths on iris first degree relative w/ NF1
What are treatment options for NF1?
Monitor optical nerves
Avoid unnecessary surgery
Treat malignancies
What is the genetic basis of Fragile X syndrome?
Loss-of-function mutation of the gene FMR1 on the X chromosome
Caused by repeat expansion of CGG repeats in 5’ untranslated region of FMR1
FRM1 protein critical in organization and formation of brain synapses
- NON MENDELLIAN
What are some symptoms of Fragile X syndrome?
Intellectual disability
Macrocephaly
Hypotonia (muscle weakness)
Macro-orchidism (large testicles)
How does genetic anticipation relate to Fragile X syndrome?
FXS caused by expanded non-coding CGG repeats in FRM1 gene
Repeat length is correlated with severity of disease
Repeat length increases with successive generations
What is the genetic basis of myotonic dystrophy?
Repeat expansion of CTG repeats in 3’ untranslated region of DMPK (Dominant/Dominant-negative)
- NON MENDELLIAN
What are some symptoms of myotonic dystrophy?
Myotonia (inability to relax muscles)
Intellectual disability
Cataracts
Arrhythmia
Turner Syndrome
45 X
Lack of an X chromosome
