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.

Silver-Russell 综合征 (SRS) 是一种先天性疾病，其特征是产前和产后生长障碍和颅面特征。在 50% 的 SRS 患者中观察到H19/IGF2：IG 差异甲基化区域 ( H19 LOM) 的低甲基化，15% 的H19 LOM的 SRS 患者有多位点印迹障碍 (MLID)。Schimke 免疫骨发育不良 (SIOD) 以脊椎骨骺发育不良和肾病为特征，是一种常染色体隐性遗传疾病，由 2 号染色体上的SMARCAL1突变引起。我们报告了一名具有典型 SRS 相关特征、脊椎骨骺发育不良和严重肾病的患者。分子分析显示H19LOM，2 号染色体的父系单亲异构体 (iUPD(2)pat)，以及SMARCAL1中父系遗传的纯合移码变体。全基因组甲基化分析显示该患者存在 MLID，尽管在另一名无 SRS 表型的 SIOD 患者中未显示 MLID。这些结果表明 iUPD(2)pat 揭示了 SMARCAL1 中的隐性突变，并且SMARCAL1基因突变可能对患者的甲基化缺陷没有直接影响。