Description of deletion/duplication based on MLPA results
18 views
Skip to first unread message
Peter Vasovcak
Feb 25, 2026, 10:44:08 AM (14 days ago) Feb 25
to HGVS Nomenclature
Hello, I have checked recommendations for description of the deletion/duplication based on MLPA probes for the whole gene. There is an example of DMD gene for this scenario. For a deletion there is example "NC_000023.11:g.(?_31120496)_(33339477_?)del
a deletion of the entire DMD gene based on a MLPA assay where the nucleotide positions g.31120496 and g.33339477 are defined by the first nucleotide of the probe 3' of the ligation site for, respectively, the last and first exons tested. What I miss is MLPA version with probes used for this description. I have used DMD probe mix P035 B1-V2 where the probes for first exon are LPO-CCACAGAAGCCCATGAACTGTGTTTCCATCCTTTGCA
RPO-TTTCTCTGCGAGTAGTTCCACACAGGTTTGTAAGTAAGTAA
and for last exon is a combination: LPO-CCTTTCTGGTTCCCAGCAGTCGGCAGTAATAGA
RPO-ATGCTTTCAGGAAGATGACAGAATCAGGAGAAAGATGCTGTTT
First question: Is genomic position g.33339477 for the first nucleotide of the probe 3' of the ligation site for last exon correct? Should not be a number g.33339377?
Second question, are genomic position same for duplication? Should not be the first duplicated nucleotide with position g.31120495, the last nucleotide of the probe 5' of the ligation site for first exon? Without this nucleotide probe could not ligate to each other. Thanks for explanation.
a deletion of the entire DMD gene based on a MLPA assay where the nucleotide positions g.31120496 and g.33339477 are defined by the first nucleotide of the probe 3' of the ligation site for, respectively, the last and first exons tested. What I miss is MLPA version with probes used for this description. I have used DMD probe mix P035 B1-V2 where the probes for first exon are LPO-CCACAGAAGCCCATGAACTGTGTTTCCATCCTTTGCA
RPO-TTTCTCTGCGAGTAGTTCCACACAGGTTTGTAAGTAAGTAA
and for last exon is a combination: LPO-CCTTTCTGGTTCCCAGCAGTCGGCAGTAATAGA
RPO-ATGCTTTCAGGAAGATGACAGAATCAGGAGAAAGATGCTGTTT
First question: Is genomic position g.33339477 for the first nucleotide of the probe 3' of the ligation site for last exon correct? Should not be a number g.33339377?
Second question, are genomic position same for duplication? Should not be the first duplicated nucleotide with position g.31120495, the last nucleotide of the probe 5' of the ligation site for first exon? Without this nucleotide probe could not ligate to each other. Thanks for explanation.
Peter
Johan den Dunnen
Feb 26, 2026, 4:23:28 AM (13 days ago) Feb 26
to HGVS Nomenclature
Dear Peter,
indeed, the description of the MLPA-detected deletion/duplication variants is influenced by the probes used, i.e. the version of the MLPA-kit when probe sequences are changed.
Based on the probe sequences you give, I get to NC_000023.11:g.31120396 and NC_000023.11:g.33339377 as the position of "the first nucleotide of the probe 3' of the ligation site".
These positions do not differ to describe a deletion or duplication of the entire gene (MLPA does not detect the duplication breakpoint).
Best regards,
Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)
Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)
Op woensdag 25 februari 2026 om 16:44:08 UTC+1 schreef Peter Vasovcak:
Reply all
Reply to author
Forward
0 new messages