Table 7. [CNBP-Specific Laboratory Technical Considerations]. - GeneReviews®

Technical Issue	Comment [Reference]
Sequence of repeat	(TG)_n(TCTG)_n(CCTG)_n: All 3 repeat tracts (TG, TCTG, & CCTG) are present in all normal & pathogenic alleles. TG & TCTG repeat tracts are highly polymorphic; for methods other than sequencing, allele sizes are reported in overall bp length rather than CCTG repeat number. Sequence variation w/in (TG)_n(TCTG)_n(CCTG)_n: The CCTG repeat tract in normal alleles typically contains ≥1 tetranucleotide interruptions (TCTG or GCTG) [Liquori et al 2003]. CCTG sequence interruptions are routinely found on normal alleles, but not pathogenic CCTG expansions, suggesting that loss of these interruptions from normal alleles may ↑ instability & predispose to germline expansion.
Methods to detect expanded allele	Methods to detect (TG)_n(TCTG)_n(CCTG)_n repeat expansion by Southern blotting & repeat-primed PCR (RP-PCR) have been described [Liquori et al 2001, Radvanszky et al 2013, Mahyera et al 2018].
Somatic instability	Abnormal CCTG repeat size ↑ w/age. >25% of affected individuals have ≥2 CCTG expansion sizes detectable in peripheral blood. Somatic heterogeneity of CCTG repeat size makes it difficult to establish a pathogenic threshold [Liquori et al 2001, Day et al 2003].
Germline instability	During germline transmission (TG)_n(TCTG)_n(CCTG)_n repeat length sometimes ↓ dramatically. No significant difference by sex of transmitting parent [Day et al 2003]

Technical Issue

Comment [Reference]

Sequence of repeat

(TG)_n(TCTG)_n(CCTG)_n:

All 3 repeat tracts (TG, TCTG, & CCTG) are present in all normal & pathogenic alleles.
TG & TCTG repeat tracts are highly polymorphic; for methods other than sequencing, allele sizes are reported in overall bp length rather than CCTG repeat number.

Sequence variation w/in (TG)_n(TCTG)_n(CCTG)_n:

The CCTG repeat tract in normal alleles typically contains ≥1 tetranucleotide interruptions (TCTG or GCTG) [Liquori et al 2003].
CCTG sequence interruptions are routinely found on normal alleles, but not pathogenic CCTG expansions, suggesting that loss of these interruptions from normal alleles may ↑ instability & predispose to germline expansion.

Methods to detect
expanded allele

Methods to detect (TG)_n(TCTG)_n(CCTG)_n repeat expansion by Southern blotting & repeat-primed PCR (RP-PCR) have been described [Liquori et al 2001, Radvanszky et al 2013, Mahyera et al 2018].

Somatic instability

Abnormal CCTG repeat size ↑ w/age.
>25% of affected individuals have ≥2 CCTG expansion sizes detectable in peripheral blood.
Somatic heterogeneity of CCTG repeat size makes it difficult to establish a pathogenic threshold [Liquori et al 2001, Day et al 2003].

Germline instability

During germline transmission (TG)_n(TCTG)_n(CCTG)_n repeat length sometimes ↓ dramatically.
No significant difference by sex of transmitting parent [Day et al 2003]

From: Myotonic Dystrophy Type 2

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