Journal Article

A patient with Silver-Russell syndrome with multilocus imprinting disturbance, and Schimke immuno-osseous dysplasia unmasked by uniparental isodisomy of chromosome 2

Fukami, Maki, Ogata, Tsutomu, Yamaguchi, Tomomi, Kosho, Tomoki, Hara-Isono, Kaori, Wakui, Keiko, Kurosawa, Kenji, Matsubara, Keiko, Kagami, Masayo, Hamada, Riku, Shimada, Shun, Miyazaki, Osamu, Muroya, Koji

2021

Overview

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.

• Publisher: Nature Publishing Group
• Subject: Arteriosclerosis - complications / Arteriosclerosis - genetics / Arteriosclerosis - physiopathology / Child / Child, Preschool / Chromosome 2 / Chromosomes / Chromosomes, Human, Pair 2 - genetics / DNA Helicases - genetics / DNA methylation / DNA Methylation - genetics / Dysplasia / Female / Genome, Human - genetics / Genomes / Genomic imprinting / Genomic Imprinting - genetics / Hereditary diseases / Humans / Immunoglobulins / Infant, Newborn / Insulin-like growth factor II / Male / Mutation / Nephropathy / Nephrotic Syndrome - complications / Nephrotic Syndrome - genetics / Nephrotic Syndrome - physiopathology / Osteochondrodysplasias - complications / Osteochondrodysplasias - genetics / Osteochondrodysplasias - physiopathology / Phenotype / Phenotypes / Physical growth / Point mutation / Primary Immunodeficiency Diseases - complications / Primary Immunodeficiency Diseases - genetics / Primary Immunodeficiency Diseases - physiopathology / Pulmonary Embolism - complications / Pulmonary Embolism - genetics / Pulmonary Embolism - physiopathology / Silver-Russell Syndrome - complications / Silver-Russell Syndrome - genetics / Silver-Russell Syndrome - physiopathology / Uniparental Disomy - genetics / Uniparental Disomy - physiopathology