monogenic diseases - pathogenesis

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• mutation in FGFR3 → inhibition of chondroblast proliferation → limited ossification → dwarfism achondroplasia
• mutation in FRFG3 → overactive FGFR3 protein → dysfunctional ossification hypochondroplasia, thanatophoric dysplasia
• heterozygous K650M mutation in FGFR3 → increase in corresponding receptor kinase activity → strong activation of FGFR3 saddan
• allelic variant of LDLR → loss of function → no/decreased uptake of LDL into extrahepatic tissues → increased cholesterol concentration in blood → accumulation in skin or arteries familial hypercholesterolemia
• mutation of PPOX → changes in single aa in protoporphyrinogen oxidase → heme not synthesized → accumulation of porphyrin precursors →body requests more heme → cycle variegate porphyria
• allelic variant C282Y → degradation of HFE protein allelic variant C282Y → degradation of HFE protein → impaired control of iron uptake by intestines → too much iron absorbed → altered distribution throughout body → accumulation of iron → organ damage haemochromatosis
• malfunctioning CFTR encoding chloride channel → abnormal transport of Cl/Na → reduced secretion of fluid/salt → obstruction of exocrine outflow from pancreas, accumulation of thick, dehydrated mucous in airways/ducts cystic fibrosis
• deficiency in phenylalanine hydroxylase → AR, inborn error of metabolism phenylketonuria
• allelic variants in LAMP2 → no/minor production of LAMP2 protein → fusion between autophagosomes and lysosomes occurs slowly → accumulation of autophagosomes (if in muscle → muscle degradation → muscle weakness) danon disease
• deletion of AZF → no/decreased development of sperm cells azoospermia, oligozoospermia
• deletion of SHOX → disruption of normal bone development and growth leri weil syndrome
• malfunctioning OPN1LW → abnormal opsin (protein in cones in retina containing photopigment) → impaired red-green vision, altered dot structure daltonism
• factor VIII/IX is absent (not produced properly or produced in reduced amounts) → interuption of cascade → deficiency in coagulation activity → continuous bleeding haemophilia A and B

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