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12 Cards in this Set
- Front
- Back
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Osteogenesis Imperfecta (OI)
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Type 1 = premature stop codon, reduce alpha1 chains by 1/2
(mild blue sclera, short, hearing loss) Type 2-4 = Gly substitution (2 = multiple fractures and lethal, 3 = thin ribs, short, 4 = mild/moderate bone deformity) |
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other collagen mutation diseases beside Osteogenesis Imperfecta
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Achondroplasia = FGFR3 substitution mutations resulting in constitutive activation. Causes inhibition of chondrocyte diff and prolif.
Short limbs, normal intelligence, fertility problems Craniosynostosis = various mutations in FGFR 1/2/3 resulting in premature closure of cranial sutures (fused digits, broad index finger, intracranial hypertension) |
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examples of clinical syndromes that involve aneuploidy or changes in chromosome structure
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Trisomy 16=spontaneous abortion
Trisomy 21=Down Trisomy 18 = Edwards (mortality) Trisomy 13 = Patau (mortality) Turner = 45X only viable monosomy Klinefelter = 47XXY male phenotype 47 XYY = male phenotype Triple X = female phenotype Aneuploidy of sex chromosomes are more common, Most autosomal aneuploidies are incompatible with life (monosomy of autosomes is lethal) |
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Explain the basic system of chromosome nomenclature
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45 XY,rob(14q,21q)
45 XY, -14, -21, +t(14q,21q) / mosaic r ring i isochromosome ter = terminal end of chromsome mar = marker unidentified chromo |
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Describe how abnormalities in chromosome number and structure occur
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Aneuploidy results from nondisjunction in M1, or M2 or mitosis
Turner 45X = Loss of Y or X during meiosis in father Klinefelter 47XXY Maternal non-disjunction / Paternal non-disjunction 47, XYY = paternal nondisjunction of Y's Triple X (47, XXX) = maternal nondisjunction |
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Chromsome abnormalities
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p arm (short) vs q arm (long)
metacentric, submetacentric, acrocentric (13,14,15,21,22) chromosome disorders more common than mendelian single gene disorders Types: numerical (aneuploidy, polyploidy), structure (translocation, inversion, insertion, deletion), autosome vs sex chromsome abnormalities euploidy = addition or loss of complete sets of chromosomes |
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Describe the difference between balanced and unbalanced chromosome rearrangement
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Balanced abnormalities do not change gene dosage (inversion, translocation)
Unbalanced abnormalities alter gene dosage (deletion, duplication, isochromosomes, ring chromosomes) |
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Inversions
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Inversions (pericentric includes centrometer, paracentric not)
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Translocations
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Reciprocal translocation (balanced aka no loss of genetic material but wrong combination forming der chromosome)
Nonreciprocal = unbalanced where parts are not swapped but instead part of one chromo move to another Robertsonian = acrocentric chromosomes (fusion of two chromsomes with loss of short arms). If occurs between 21 and 22 can cause trisomy 21. |
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Unbalanced rearrangements
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Deletions: Williams, DiGeorge, Angelman and Prader-Willi, loss of material at the end of the short arm of chromosome 5. It causes “Cri di Chat” syndrome.
Isochromosomes A chromosome can split "the wrong way" in mitosis (or meiosis II) so that both long arms remain attached and move to one pole, and both short arms do likewise moving to the other pole. Ring chromosomes A mutation event which removes both telomeres can be repaired by sealing the ends together forming a ring chromosome. |
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Explain the etiology of somatic and germline mosaicism
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??
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Explain how mutations affect several features of procollagen maturation and therefore influence the pathophysiology of Osteogenesis Imperfecta (OI)
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answer later
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