Disease relevance of CCT3

• Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9 [1].

High impact information on CCT3

• We estimate the age of the founding haplotype and of the DM2 (CCTG) expansion mutation to be approximately 200-540 generations [2].
• The mutations are flanked by short direct repeats, and the breakpoints are within 5 nt of a CCTG (CAGG) sequence [3].
• The DNA sequence unit CCTG is repeated five times in exon 1 which is composed exclusively of untranslated sequence [4].
• A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy: CCTG 575 [5].
• The human TRiC-P5 gene (TRIC5) maps to human chromosome 1q23, a region known to be a preferential chromosomal breakpoint involved in leukemia [6].

Biological context of CCT3

• The first exon of the gene is highly GC rich and contains many short tandem di- and trinucleotide repeats, interrupted direct repeats, and CCTG (CAGG) motifs that have been identified as hotspots for DNA deletions [3].
• This procedure exploits the fact that an SfiI cleavage site, GGCCGCCT/CGGCC (the recognition sequences are underlined), is present at the SV40 replication origin and the cleaved ends, CCT-3' and AGG-3', are not rotationally equivalent [7].
• BACKGROUND: Proximal myotonic myopathy is an autosomal dominant multisystem disorder with a recently defined CCTG expansion on chromosome 3 in the major subgroup (myotonic dystrophy type 2) [8].
• 3. Myotonic dystrophy type 2 (DM2) is caused by an unstable expansion of a CCTG tetraplet repeat in intron 1 of the zinc finger 9 (ZFN9 gene) on chromosome 3q 21 [9].
• Recently, genetic confirmation has become available with the identification of the molecular defect, an expansion of a CCTG repeat located in intron 1 of the zinc finger protein 9 (ZNF9) gene [10].

Anatomical context of CCT3

• At present, foci of accumulated noncoding CCTG repeat RNA (ribonuclear inclusions) in the cell nuclei are thought to interfere with the regulation and expression of several genes at the basis of multisystemic aspects of myotonic dystrophy type 2 [9].

Analytical, diagnostic and therapeutic context of CCT3

• Southern-blot analysis has also revealed the Cctg gene to be highly conserved in mouse, rat, sheep and frog [11].
• Sequence analysis of the deletion demonstrated a 7-bp repeat sequence (GAGGACA) both 5' to the deletion and at the 3' end of the deletion, a 4-bp palindromic sequence (ACAG vs. CTGT) bracketing the deletion, and a novel inserted 4-bp sequence (CCTG) at the breakpoint, suggesting that the mechanism of the deletion may have been "slipped mispairing."[12]

References