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A patient with Silver-Russell syndrome with multilocus imprinting disturbance, and Schimke immuno-osseous dysplasia unmasked by uniparental isodisomy of chromosome 2.
- Source :
-
Journal of human genetics [J Hum Genet] 2021 Nov; Vol. 66 (11), pp. 1121-1126. Date of Electronic Publication: 2021 May 24. - Publication Year :
- 2021
-
Abstract
- Silver-Russell syndrome (SRS) is a congenital disorder characterized by prenatal and postnatal growth failure and craniofacial features. Hypomethylation of the H19/IGF2:IG-differential methylated region (H19LOM) is observed in 50% of SRS patients, and 15% of SRS patients with H19LOM had multilocus imprinting disturbance (MLID). Schimke immuno-osseous dysplasia (SIOD), characterized by spondyloepiphyseal dysplasia and nephropathy, is an autosomal recessive disorder caused by mutations in SMARCAL1 on chromosome 2. We report a patient with typical SRS-related features, spondyloepiphyseal dysplasia, and severe nephropathy. Molecular analyses showed H19LOM, paternal uniparental isodisomy of chromosome 2 (iUPD(2)pat), and a paternally inherited homozygous frameshift variant in SMARCAL1. Genome-wide methylation analysis showed MLID in this patient, although it showed no MLID in another patient with SIOD without SRS phenotype. These results suggest that iUPD(2)pat unmasked the recessive mutation in SMARCAL1 and that the SMARCAL1 gene mutation may have no direct effect on the patient's methylation defects.<br /> (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)
- Subjects :
- Arteriosclerosis complications
Arteriosclerosis physiopathology
Child
Child, Preschool
Chromosomes, Human, Pair 2 genetics
Female
Genome, Human genetics
Genomic Imprinting genetics
Humans
Infant, Newborn
Male
Nephrotic Syndrome complications
Nephrotic Syndrome physiopathology
Osteochondrodysplasias complications
Osteochondrodysplasias physiopathology
Phenotype
Primary Immunodeficiency Diseases complications
Primary Immunodeficiency Diseases physiopathology
Pulmonary Embolism complications
Pulmonary Embolism physiopathology
Silver-Russell Syndrome complications
Silver-Russell Syndrome physiopathology
Uniparental Disomy genetics
Uniparental Disomy physiopathology
Arteriosclerosis genetics
DNA Helicases genetics
DNA Methylation genetics
Nephrotic Syndrome genetics
Osteochondrodysplasias genetics
Primary Immunodeficiency Diseases genetics
Pulmonary Embolism genetics
Silver-Russell Syndrome genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1435-232X
- Volume :
- 66
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 34031513
- Full Text :
- https://doi.org/10.1038/s10038-021-00937-7