» Articles » PMID: 26377239

Kagami-Ogata Syndrome: a Clinically Recognizable Upd(14)pat and Related Disorder Affecting the Chromosome 14q32.2 Imprinted Region

Overview
Journal J Hum Genet
Specialty Genetics
Date 2015 Sep 18
PMID 26377239
Citations 54
Authors
Affiliations
Soon will be listed here.
Abstract

Human chromosome 14q32.2 carries paternally expressed genes including DLK1 and RTL1, and maternally expressed genes including MEG3 and RTL1as, along with the germline-derived DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the postfertilization-derived MEG3-DMR. Consistent with this, paternal uniparental disomy 14 (upd(14)pat), and epimutations (hypermethylations) and microdeletions affecting the IG-DMR and/or the MEG3-DMR of maternal origin, result in a unique phenotype associated with characteristic face, a small bell-shaped thorax with coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly and polyhydramnios. Recently, the name 'Kagami-Ogata syndrome' (KOS) has been approved for this clinically recognizable disorder. Here, we review the current knowledge about KOS. Important findings include the following: (1) the facial 'gestalt' and the increased coat-hanger angle constitute pathognomonic features from infancy through childhood/puberty; (2) the unmethylated IG-DMR and MEG3-DMR of maternal origin function as the imprinting control centers in the placenta and body respectively, with a hierarchical interaction regulated by the IG-DMR for the methylation pattern of the MEG3-DMR in the body; (3) RTL1 expression level becomes ~2.5 times increased in the absence of functional RTL1as-encoded microRNAs that act as a trans-acting repressor for RTL1; (4) excessive RTL1 expression and absent MEG expression constitute the primary underlying factor for the phenotypic development; and (5) upd(14)pat accounts for approximately two-thirds of KOS patients, and epimutations and microdeletions are identified with a similar frequency. Furthermore, we refer to diagnostic and therapeutic implications.

Citing Articles

Prenatal diagnosis of recurrent Kagami-Ogata syndrome inherited from a mother affected by Temple syndrome: a case report and literature review.

Yang X, Li M, Qi Q, Zhou X, Hao N, Lu Y BMC Med Genomics. 2024; 17(1):222.

PMID: 39210340 PMC: 11360317. DOI: 10.1186/s12920-024-01987-4.


Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis.

Mackay D, Gazdagh G, Monk D, Brioude F, Giabicani E, Krzyzewska I Clin Epigenetics. 2024; 16(1):99.

PMID: 39090763 PMC: 11295890. DOI: 10.1186/s13148-024-01713-y.


The long non-coding RNA Meg3 mediates imprinted gene expression during stem cell differentiation.

Farhadova S, Ghousein A, Charon F, Surcis C, Gomez-Velazques M, Roidor C Nucleic Acids Res. 2024; 52(11):6183-6200.

PMID: 38613389 PMC: 11194098. DOI: 10.1093/nar/gkae247.


Polyhydramnios associated with rare genetic syndromes: two case reports.

Lim C, Lustestica I, Poon W, Tan W J Med Case Rep. 2024; 18(1):97.

PMID: 38369506 PMC: 10875787. DOI: 10.1186/s13256-024-04435-0.


Imprinting disorders.

Eggermann T, Monk D, Perez de Nanclares G, Kagami M, Giabicani E, Riccio A Nat Rev Dis Primers. 2023; 9(1):33.

PMID: 37386011 DOI: 10.1038/s41572-023-00443-4.


References
1.
Coveler K, Yang S, Sutton R, Milstein J, Wu Y, Beischel L . A case of segmental paternal isodisomy of chromosome 14. Hum Genet. 2002; 110(3):251-6. DOI: 10.1007/s00439-002-0688-4. View

2.
Kagami M, Kurosawa K, Miyazaki O, Ishino F, Matsuoka K, Ogata T . Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami-Ogata syndrome). Eur J Hum Genet. 2015; 23(11):1488-98. PMC: 4613461. DOI: 10.1038/ejhg.2015.13. View

3.
Murphy S, Wylie A, Coveler K, Cotter P, Papenhausen P, Sutton V . Epigenetic detection of human chromosome 14 uniparental disomy. Hum Mutat. 2003; 22(1):92-7. DOI: 10.1002/humu.10237. View

4.
Seitz H, Youngson N, Lin S, Dalbert S, Paulsen M, Bachellerie J . Imprinted microRNA genes transcribed antisense to a reciprocally imprinted retrotransposon-like gene. Nat Genet. 2003; 34(3):261-2. DOI: 10.1038/ng1171. View

5.
Stevenson D, Brothman A, Chen Z, Bayrak-Toydemir P, Longo N . Paternal uniparental disomy of chromosome 14: confirmation of a clinically-recognizable phenotype. Am J Med Genet A. 2004; 130A(1):88-91. DOI: 10.1002/ajmg.a.30200. View