nur rohmah 12/338710/pmu/7375
DESCRIPTION
GENOTYPE–PHENOTYPE CORRELATIONS IN NONLETHAL OSTEOGENESIS IMPERFECTA CAUSED BY MUTATIONS IN THE HELICAL DOMAIN OF COLLAGEN TYPE I Frank Rauch, Liljana Lalic, Peter Roughley and Francis H Glorieux. Nur Rohmah 12/338710/PMU/7375. Introduction. Introduction. Introduction. Hearing loss. - PowerPoint PPT PresentationTRANSCRIPT
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GENOTYPE–PHENOTYPE CORRELATIONS IN NONLETHAL OSTEOGENESIS IMPERFECTA CAUSED BY MUTATIONS IN THE HELICAL
DOMAIN OF COLLAGEN TYPE I
Frank Rauch, Liljana Lalic, Peter Roughley and Francis H Glorieux
Nur Rohmah12/338710/PMU/7375
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Introduction
Osteogenesis Imperfecta
heritable connective
tissue disorder
mutation in COL1A1 or
COL1A2
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Introduction
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Introduction
Osteogenesis Imperfecta (OI)
Blue/grey sclera
Dentinogenesis imperfectabone fragility
Hearing loss
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Introduction
Type I < IV < III < II
Type Clinical severity Typical features
I Mild non-deforming OI Normal height or mild short stature; blue sclera; no dentinogenesis imperfecta
II Perinatal lethal Multiple rib and long-bone fractures at birth; pronounced deformities; broad long bones, low density of skull bones on radiographs; dark sclera
III Severely deforming Very short; triangular face; severe scoliosis; greyish sclera; dentinogenesis imperfecta
IV Moderately deforming Moderately short; mild to moderate scoliosis; greyish or white sclera; dentinogenesis imperfecta
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Objective
to investigated genotype–phenotype correlations in OI patients with glycine mutations in the triple helical domain of collagen type I.
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Subject and method
Sample Patient Clinical characteristics
Total genomic DNA was
isolated from peripheral blood
Amplified by PCR and
sequencing
aligned with the GenBank reference
sequences
Statistical analysis
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Subject and method
Sampel Patient
• 161 OI patients
DNA isolation
• Total genomic DNA was isolated from peripheral blood using the QIAamp DNA Blood Midi Kit
Collagen type I
mutation analysis
• All exons of the COL1A1 and COL1A2 genes amplified by PCR. The sequencing reactionusing a BigDye Terminator cycle sequencing kit . The nucleotide sequence was determined using an Applied Biosystems 3100 DNA sequencer.
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Subject and method
Sequence traces were aligned with the GenBank reference sequencesCOL1A1 genomic DNA (AF017178) COL1A2 genomic DNA (AF004877.1), then compared and analyzed using BLAST.
Alignment
Statistical analysis
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RESULTS AND DISCUSSION
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RESULTS AND DISCUSSION
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RESULTS AND DISCUSSION
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Figure 1 Relationship between the triple helical position of glycine mutations in collagen type I a chains and the presence (+) or absence () of deformities or fractures at birth (DFB), blue sclera (BS), and dentinogenesis imperfecta (DI).
RESULTS AND DISCUSSION
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Figure 2. Relationship between the positions of glycine substitutions in the triple helical domain of type I collagen and height z-scores
RESULTS AND DISCUSSION
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Conclusion
• genotype–phenotype correlations for 161 OI patients with 111 distinct triple helical mutations of collagen type I
• Height correlated with the location of the mutation in the α2 chain but not in the α1.
• Patients with mutations affecting the first 120 amino acids at the amino-terminal end of the collagen type I triple helix had blue sclera but did not have dentinogenesis imperfecta.
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Manual Rumus Z-score :Z= X-M SDDimana: Z = Nilai standar
X = Rata-rata distribusiM = Nilai mentah yang akan dicari
nilai standarnyaSD = Standar deviasi distribusi
Rumus Z-score :
SDM-X Z