L7 - Neurological Disease Flashcards
Two congenital disorders of axon pathfinding
CRASH Syndrome
Horizontal Gaze Plasy with Progressive Scoliosis (HGPPS)
What molecule is implicated with CRASH syndrome
L1CAM
A cell adhesion molecule
Descrube L1CAM
An adhesion molecule related to TAg-1 and NrCAM
Encoded by an X-linked gene
Mitations in L1 lead to …
BROAD SPECTRUM OF NEUROLOGICAL DISEASE including …
Hydrocephalus Mental Retardation (MASA) Spastic Paraplegia (SPG1)
Mutations in L1CAM affect….
1 in 30’000
Mutations in L1CAM charactersited by
Defects in axon pathfinding at the pyramidal decussation
What is the cause of spastic paraplegia
Failute of the corticospinal tract to project beyond cervical regions
What is the main symptom of spastic paraplegia
uncontrolled reflexes in the lower limbs
What gene is found mutated in HGPPS
Robo3 - this is rare
Describe what is seen to be abnormal in HGPPS
Several commissures not just the spinal cords
Crossed fibres tracts in the pons are reposnible for coordination of eye movmem
What is a disease causes by an indirect effect of axon pathfinding defects
Kallmann’s Syndrome
Symptoms of Kallmanns syndrome
Congenital anosmia and hypogonadism
Cause of Kallmanns syndrome
GnRH neurones fai to migrate to the hypothalamus
This is the cause of HYPOGONADISM
What mutations have been linked to Kallmanns syndrome
Adhesion - KAL1
FGFR1 and FGF8
Sema3A Sema7A
What is SEMA3a regiored for
Primary defect in Sema3A KO
Link Sema3A mutants to Kallmanns disease
Required for OLFACTORY EPITHELIAL AXON GUIDANCE
Primary ddefect is OE neuron axon guidance
Normally GnRH migrate along these Sema3A tracts to hypothalamus so these migrate abberantly in Sema3A mutants
