Abstract |
Methylation-specific (MS) multiplex ligation-dependent probe amplification (MLPA) at two differentially methylated regions (DMRs) at chromosome 11p15, H19-DMR and LIT1-DMR, and microsatellite analysis for uniparental disomy (UPD) at chromosome 7 or 11, have been recommended for the genetic diagnosis of the Beckwith-Wiedemann syndrome (BWS) and the Silver-Russell syndrome (SRS). In this study, the efficacy of the MS pyrosequencing method at H19-DMR and LIT1-DMR at 11p15 and SGCE-DMR at 7q21 was evaluated for the genetic diagnosis of BWS (n=18) and SRS (n=20) patients. Epigenetic alterations or UPD were detected in 83% of BWS and 50% of SRS individuals by MS-MLPA, but the detection rate increased to 95% of BWS and 70% of SRS by MS pyrosequencing. Thirteen BWS patients (72%) harbored loss-of-methylation (LOM) at LIT1-DMR and two patients (11%) harbored gain-of-methylation (GOM) at H19-DMR, whereas two patients (11%) had both LOM at LIT1-DMR and GOM at H19-DMR, reflecting paternal UPD 11. Thirteen SRS patients (65%) harbored LOM at H19-DMR, whereas one patient (5%) had GOM at SGCE-DMR, reflecting maternal UPD 7. Birth anthropometric profiles were significantly correlated to methylation scores at either H19-DMR or LIT1-DMR. In conclusion, MS pyrosequencing enhanced the detection rate of molecular defects in BWS and SRS. Moreover, it indicates that methylation status at 11p15.5 might have an important role in fetal growth.
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Authors | Beom Hee Lee, Gu-Hwan Kim, Tae Jeong Oh, Joo Hyun Kim, Jin-Joo Lee, Seung Hoon Choi, Joo Yeon Lee, Jae-Min Kim, In Hee Choi, Yoo-Mi Kim, Jin-Ho Choi, Han-Wook Yoo |
Journal | Journal of human genetics
(J Hum Genet)
Vol. 58
Issue 9
Pg. 604-10
(Sep 2013)
ISSN: 1435-232X [Electronic] England |
PMID | 23803580
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Topics |
- Beckwith-Wiedemann Syndrome
(diagnosis, genetics)
- Chromosomes, Human, Pair 11
(genetics)
- Chromosomes, Human, Pair 7
(genetics)
- DNA Methylation
(genetics)
- DNA Mutational Analysis
- Epigenesis, Genetic
- Female
- Humans
- Infant, Newborn
- Male
- Multiplex Polymerase Chain Reaction
- Pedigree
- Silver-Russell Syndrome
(diagnosis, genetics)
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