Basic Developmental Biology Deck 4 Flashcards
What disease is characterized by dramatic forearm defects and what is the mechanism?
Holt Oram Syndrome - mutant Tbx5
What disease is characterized by limb deficiencies or duplications, apocrine/mammary gland hypoplasia and/or dysfunction, abnormal dentition, delayed puberty in males, and genital anomalies?
Ulnar-Mammary syndrome - mutant Tbx3
What disease is characterized by spike limbs?
Acheiropodia - deletion of SHH limb enhancer which is necessary for diversity of digits.
What disease is characterized by polydactyly?
Pre-axial polydactyly - activation of SHH limb enhancer on anterior side of limb, causes ectopic anterior SHH expression, same effect as transplanting ZPA.
What disease is characterized by dysplasia of the nails and absent or hypoplastic patellae as well as abnormality of the elbows interfering with pronation and supination, and in some cases nephropathy?
Nail-patella Syndrome - mutation of Lmx1b, a transcription factor activated by Wnt 7a on the dorsal surface of limbs, which ordinarily causes dorsal-ventral patterning.
What disease is characterized by axial skeletal disorders including multiple segmentation defects of the vertebrae (SDV), malalignment of the ribs with variable points of intercostal fusion, and often a reduction in rib number?
spondylocostal dysostosis - mutation in lunatic fringe (which is critical in oscillating clock of somite formation, normally inhibits Delta/Notch signaling).
What disease is characterized by abnormal vertebrae (‘butterfly’ vertebrae) and decrease in interpediculate distance in the lumbar spine, along with cardiac defects, ocular defects, bile duct defects and lots of other problems?
Alagille syndrome - defect in Jag1, a Notch ligand critical in oscillating clock of somite formation.
What disease is characterized by congenital bowing and angulation of long bones in newborns, together with other skeletal and extra skeletal defects?
Campomelic dysplasia - haplo-insufficiency of Sox9 transcription factor required for chondrogenesis.
What disease is characterized by short limbs, facial anomalies, increased bone density, and advanced skeletal maturation?
Bloomstrand chondrodysplasia - Mutations in PTHrP receptor causes chondrocytes to mature too quickly, premature ossification (no balancing of IHH signal).
What disease is characterized by open skull sutures with bulging calvaria, hypoplasia or aplasia of the clavicles permitting abnormal facility in apposing the shoulders, and often vertebral malformation?
Cleidocranial Dysplasia- haplo-insufficiency of Runx2, gene critical in most osteoblastic genes, critical in both endochondral ossification and intramembranous bone growth.
What disease is characterized by sparse hair (hypotrichosis), abnormal or missing teeth (anodontia or hypodontia), and inability to sweat (anhidrosis or hypohidrosis)?
hypohidrotic ectodermal dysplasia - EDA mutants which normally induce Wnt10b signaling which is critical for placode formation and hair follicle development.
What disease is characterized by a predisposition to basal-cell carcinoma?
Gorlin Syndrome - a mutant PTCH gene increases susceptibility to a hyperactive SHH signal. SHH ordinarily drives proliferation in the skin placode. Uncontrolled SHH signaling leads to uncontrolled cell growth.
What infectious disease causes massive dilation of the gut?
Chagas - infection of neural crest neurons, immune destruction of enteric ganglia can occur subsequent to infection.
What disease is characterized by congenital bowl obstruction?
Hirschsprung’s disease - due to inactivating mutation of Ret, a tyrosine kinase receptor that recognizes GDNF, a long range attractant of neural crest cells expressed in the cecum of the intestine.
What disease is characterized by yellow teeth and bone defects in children?
tetracycline fetal exposure.
