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Kagami–Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region
- Source :
- Journal of Human Genetics
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Chromosome Disorders
Review
Biology
Genomic Imprinting
03 medical and health sciences
Genetics
medicine
Humans
Abnormalities, Multiple
Epigenetics
Imprinting (psychology)
Genetics (clinical)
Chromosomes, Human, Pair 14
MEG3
Cytogenetics
Syndrome
Uniparental Disomy
medicine.disease
Uniparental disomy
Phenotype
030104 developmental biology
Statistical genetics
embryonic structures
Medical genetics
Chromosome Deletion
Genomic imprinting
Subjects
Details
- ISSN :
- 1435232X and 14345161
- Volume :
- 61
- Database :
- OpenAIRE
- Journal :
- Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....d199be11098d833550e14e85e05d748b