Table 1.

Molecular Genetic Testing Used in Kagami-Ogata Syndrome

MethodGenetic Mechanism 1Proportion of Probands Identified by Method 2
MS-MLPA 3upd(14)pat~50%
Epimutation (hypermethylation) of MEG3:TSS-DMR (maternal)~25%
Deletion of MEG3/DLK1:IG-DMR &/or MEG3:TSS-DMR (maternal)~20%
Deletion of RTL1as (maternal) 4~5% 5
KaryotypeTranslocations &/or inversions disrupting the integrity between the MEG3 promoter & RTL1asExtremely rare 6
Robertsonian translocations incl 14qRare

DMR = differentially methylated region; IG = intergenic; MS-MLPA = methylation-specific multiple ligation-dependent probe amplification; TSS = transcription start site; upd(14)pat = paternal uniparental disomy of chromosome 14

1.

See Molecular Genetics for more details and see Figure 4.

2.
3.

Identification of hypermethylation of MEG3:TSS-DMR establishes the diagnosis of Kagami-Ogata syndrome. However, deletion analysis (included in MS-MLPA) and parent-of-origin analysis are required to distinguish upd(14)pat, epimutation, and deletions involving the DMRs.

4.

Parent-of-origin analysis is necessary to confirm that the RTL1as deletion is present on the maternally inherited chromosome 14.

5.

Deletion of RTL1as (maternal) without deletion of MEG3/DLK1:IG-DMR or MEG3:TSS-DMR has been identified in five individuals with Kagami-Ogata syndrome. The frequency of such deletions may be overestimated, because of the publication bias that such a rare condition would be reported preferentially.

6.

A translocation disrupting the integrity between the maternally inherited MEG3 promoter at the MEG3:TSS-DMR and RTL1as has been identified in one individual with Kagami-Ogata syndrome.

From: Kagami-Ogata Syndrome

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