DLA 7 Flashcards
symptoms of achondroplasia
short arms and legs with a normal torso reduced height large head size, flat bridge of nose short fingers trident hand
what leads to achondroplasia
a gain of function mutation in the FGFR3 gene
FGFR3 is a tyrosine kinase receptor
function of FGFR3-R
A transmembrane tyrosine kinase
promotion of cartilage into bone
G380R mutation of this gene leads to unregulated activity
thus growth plate is converted into bone early
what kind of genetic disorder is achondroplasia
autosomal dominant
what do HOX genes encode?
transcription factors
may be homodimers or heterodimers
how are HOX genes arranged?
in clusters
disorder associated with HOX gene mutations?
extra cervical rib
polydactyly
increased risk of cancer
lots more
what is the role of sonic hedgehog (SHH)
induce cell proliferation and tissue patterning
expressed at different developmental points
signaling pathway of SHH
SHH is cleaved into an active N-terminal form and cholesterol is added
SHH binds to PTCH receptor which un-inhibits SMO
SMO activates GLI
GLI and CREBBP interact and activate gene expression
heterozygous mutation of SHH?
leads to haploinsufficency of SHH
thus holoprosencephaly may occur
loss of function mutation (AD)
mainly have facial abnormalities
what could lead to hypertelorism? SHH??
increasing SHH expression in the frontal nasal prominence, thus expansion of the face
increased space between eyes
preaxial polydactyly and SHH
overexpression of SHH in the limb bud
Smith-Lemi-Opitz Syndrome
Mutation in gene encoding 7-dehydrocholestrol reductase
Microcephaly, mental impairment, malformation of
mesodermal origin, syndactyly, and polydactyly
what is a malformation?
example?
due to an abnormal developmental process
ex: cleft lip/ palate, polydactyly
what is a sequence (malformation sequence)? example?
A cascade of effect resulting from a single primary malformation
Ex: Pierre robin sequence of head and face abnormalities
