1. 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

2. Introduction heritable connective tissue disorder
Osteogenesis Imperfecta
heritable connective tissue disorder
mutation in COL1A1 or COL1A2

3. Introduction

4. Introduction Hearing loss Osteogenesis Imperfecta (OI)
Blue/grey sclera
bone fragility
Dentinogenesis imperfecta

5. 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

6. Objective
to investigated genotype–phenotype correlations in OI patients with glycine mutations in the triple helical domain of collagen type I.

7. 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

8. Collagen type I mutation analysis
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 reactionusing a BigDye Terminator cycle sequencing kit . The nucleotide sequence was determined using an Applied Biosystems 3100 DNA sequencer.

9. Subject and method Alignment
Sequence traces were aligned with the GenBank reference sequencesCOL1A1 genomic DNA (AF017178) COL1A2 genomic DNA (AF ), then compared and analyzed using BLAST.
Statistical analysis

10. RESULTS AND DISCUSSION

11. RESULTS AND DISCUSSION

12. RESULTS AND DISCUSSION

13. RESULTS AND DISCUSSION
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).

14. RESULTS AND DISCUSSION
Figure 2. Relationship between the positions of glycine substitutions in the triple helical domain of type I collagen and height z-scores

15. 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.

17. Dimana: Z = Nilai standar X = Rata-rata distribusi
Rumus Z-score :
Manual Rumus Z-score :
Z= X-M SD
Dimana: Z = Nilai standar
X = Rata-rata distribusi
M = Nilai mentah yang akan dicari nilai standarnya
SD = Standar deviasi distribusi