Lecture Notes: Genetic Disorders and Protein Structures (Pages 41-67)

Vocabulary flashcards covering key disorders, mutations, and protein-structure concepts from pages 41–67.

Cystinuria

A genetic disease caused by substitutions in the kidney rBAT transporter, leading to accumulation of cystine, arginine, and lysine in the kidneys and formation of cystine stones; incidence about 1 in 7,000. Common mutations include Q268K and T341A.

rBAT transporter

Renal amino acid transporter in which mutations cause cystinuria and poor reabsorption of certain amino acids.

Cystine stones

Urinary stones formed from cystine due to impaired reabsorption in cystinuria.

Osteogenesis imperfecta

Brittle bone disease caused by COL1A1/COL1A2 mutations leading to defective type I collagen, often presenting with blue sclera. It is usually autosomal dominant and ranges from mild to lethal due to issues like glycine substitutions in the collagen triple helix. Types are classified by severity (e.g., Type I mild, Type II lethal).

Type I collagen

The main collagen in bone formed by two \alpha1 and one \alpha2 chains (encoded by COL1A1 and COL1A2); mutations disrupt bone strength.

Blue sclera

A characteristic blue-tinged sclera seen in many cases of osteogenesis imperfecta due to thin connective tissue.

Ehlers-Danlos Syndrome (EDS)

Inherited connective tissue disorders, often autosomal dominant, characterized by hyperflexible joints and skin, easy bruising, and frequent dislocations. Mutations in genes like COL5A1 and COL5A2 (affecting type V collagen or type III procollagen) contribute to various subtypes through defects such as interhelical crosslinking avoidance.

Marfan syndrome

Connective tissue disorder due to FBN1 mutations (often missense or frameshift), inherited in an autosomal dominant pattern. It is characterized by tall stature, lens dislocation (ectopia lentis), and an increased risk of aortic problems, stemming from defective fibrillin-1 and upregulated TGF-\beta signaling. The FBN1 gene is located on Chromosome 15.

Fibrillin-1

Ca^{2+}-binding glycoprotein forming elastin-containing microfibrils; structural component of connective tissue, defects in which cause Marfan syndrome.

Charcot‑Marie‑Tooth disease (CMT)

Inherited group of peripheral neuropathies affecting myelin or axons, caused by mutations in over 40 implicated proteins (e.g., PMP22, HSP22, HSP27). It is mainly autosomal dominant.

Lesch–Nyhan syndrome

X-linked recessive disorder due to hypoxanthine-guanine phosphoribosyltransferase (HPRT1) deficiency, leading to disrupted purine salvage pathway and accumulation of uric acid. Symptoms include intellectual disability, self-mutilation, and movement disorders. Mutations can involve exon skipping or deletion (e.g., Type I exon 4 skipping, Type II exon 4 deletion).

Alzheimer’s disease

Neurodegenerative disease characterized by extracellular A\beta plaques (formed from amyloid precursor protein (APP)) and intracellular neurofibrillary tangles (aggregates of hyperphosphorylated Tau protein). Some familial forms are autosomal dominant and mutations in MAPT (encoding Tau) are linked to the disease.

Huntington’s disease

Autosomal dominant neurodegenerative disease caused by CAG repeat expansion (polyQ >36) in the Huntingtin (Htt) gene, leading to progressive motor and cognitive decline.