Flashcards: Genetic Mutations and Syndromes — 48 cards

What is a genetic mutation?

A permanent alteration of the DNA sequence.

Which mutations can be inherited?

Germ-cell mutations can be inherited.

Where do somatic-cell mutations arise?

In body cells.

What environmental factor can cause somatic-cell mutations?

Radiation can cause somatic-cell mutations.

In which processes do genetic mutations participate?

Evolution, immune-system development, and cancer.

Name a major complication of genetic mutations related to pregnancy.

Spontaneous abortion.

What severe organ defects can result from genetic mutations?

Tetralogy of Fallot and renal dysplasia.

List some functional impairments caused by genetic mutations.

Visual or hearing disturbances, growth deficiency, intellectual disability, and cancer.

What is a point mutation in DNA?

A substitution of one DNA base.

What distinguishes a silent mutation from others?

It encodes the same amino acid.

What effect do deletions have on DNA?

They remove DNA bases.

What causes Mendelian disorders?

A single gene mutation with large effects.

What is required for autosomal dominant inheritance?

One mutated gene copy.

What is a transition mutation?

A substitution between two purines or two pyrimidines.

What is a transversion mutation?

A substitution between a purine and a pyrimidine.

What is the effect of nonsense mutations?

They create an early stop codon producing a nonfunctional protein.

What type of disorder is Alagille syndrome?

An autosomal dominant disorder.

Which gene is involved in about 95% of Alagille syndrome cases?

The JAG1 gene on chromosome 20p12.

Which gene mutation in Alagille syndrome is linked to renal malformations?

NOTCH2 mutations on chromosome 1p13.

What causes chronic cholestasis in Alagille syndrome?

Loss of intrahepatic bile ducts.

Name a characteristic skeletal feature of Alagille syndrome.

Butterfly-shaped or hemivertebrae.

What cardiac defects are characteristic of Alagille syndrome?

Peripheral pulmonary artery stenosis or tetralogy of Fallot.

What ocular abnormality is seen in Alagille syndrome?

Embryotoxon.

What treatments are used for Alagille syndrome?

Ursodeoxycholic acid, cholestyramine, rifampin, naltrexone, nutritional support, biliary diversion, liver transplantation, and heart defect repair.

What are the three main features of McCune–Albright syndrome?

Fibrous dysplasia, hyperfunctioning endocrinopathy, and unilateral café-au-lait skin spots.

What genetic mutation causes McCune–Albright syndrome?

A postzygotic mutation in GNAS1 on chromosome 20q13.1–13.2.

What cellular signaling pathway is abnormal in McCune–Albright syndrome?

Gs alpha protein signaling through the G-protein, cyclic AMP, and adenylate cyclase pathway.

Which bones are commonly affected by fibrous dysplasia in McCune–Albright syndrome?

The skull base and proximal femur.

What radiographic features characterize fibrous dysplasia?

Expansile lytic lesions, cortical thinning, ground-glass appearance, and possible shepherd’s-crook deformity.

Name two endocrine manifestations of McCune–Albright syndrome.

Hyperthyroidism and Cushing’s syndrome.

What effect do bisphosphonates have on fibrous dysplasia?

They reduce pain but do not stop disease progression.

How are hormone excesses treated in McCune–Albright syndrome?

With endocrine medications targeting the hormone excesses.

What is primary ciliary dyskinesia?

A congenital autosomal recessive disease impairing ciliary motility.

Which genes affect axonemal outer dynein arms in primary ciliary dyskinesia?

DNAH5 and DNAI1 mutations affect outer dynein arms.

Which genes affect radial spokes in primary ciliary dyskinesia?

RSPH4A and RSPH9 mutations affect radial spokes.

What causes recurrent respiratory infections in primary ciliary dyskinesia?

Immotile or abnormally moving cilia cause recurrent infections.

What three conditions define Kartagener syndrome in primary ciliary dyskinesia?

Situs inversus, chronic sinusitis, and bronchiectasis define Kartagener syndrome.

Name one diagnostic method for primary ciliary dyskinesia.

Reduced or absent nasal nitric oxide can diagnose it.

What does spirometry show in primary ciliary dyskinesia diagnosis?

Spirometry shows airway obstruction.

List one treatment approach for primary ciliary dyskinesia.

Antibiotics are used in treatment.

What is Treacher Collins syndrome also called?

Mandibulofacial dysostosis or Franceschetti–Zwahlen–Klein syndrome.

What genetic mutation causes Treacher Collins syndrome?

A TCOF1 mutation on chromosome 5q32.

What cellular effects result from the TCOF1 mutation in Treacher Collins syndrome?

Treacle-protein insufficiency, impaired ribosome biogenesis, neuroepithelial apoptosis, and reduced neural crest cells.

What type of inheritance pattern does Treacher Collins syndrome have?

Autosomal dominant with variable penetrance.

What percentage of Treacher Collins syndrome cases are spontaneous?

Approximately 60%.

Name three typical craniofacial findings in Treacher Collins syndrome.

Mandibular and zygomatic hypoplasia, retrognathia, and downslanting eyelids.

What ear abnormalities are typical in Treacher Collins syndrome?

Malformed external and middle ears.

What treatments may be required for managing Treacher Collins syndrome?

Reconstructive surgery, tracheostomy, glossopexy, cleft palate correction, gastrostomy, hearing aids, and speech therapy.