The Methylation Status in the Chromosome 11p15.5 Region and Metabolic Disorders in Children with Syndromic and Nonsyndromic Intrauterine Growth Restriction

Molecular syndromology

article

Özer, Emre¹  Geyik, Filiz²  Alp Ünkar, Zeynep³  Ercan, Oya⁴  Tüysüz, Beyhan¹ 

[1] Department of Pediatric Genetics, Cerrahpasa Medical School, Istanbul University-Cerrahpasa;Department of Genetics, Aziz Sancar Experimental Medicine Research Institute, Istanbul University;Department of Neonatology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa;Department of Pediatric Endocrinology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa

关键词: 11p15 hypomethylation;    Intrauterine growth restriction;    Short stature;    Metabolic disorder;    Silver-Russell syndrome;    MLPA;   

DOI  :  10.1159/000518630

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

Loss of methylation (LoM) of the imprinting control region 1 (ICR1) in the chromosome 11p15.5 domain is detected in patients with Silver-Russell syndrome (SRS), characterized by asymmetric pre- and postnatal growth restriction, and typical craniofacial features. The patients with intrauterine growth restriction (IUGR) possess a high risk for adult metabolic problems. This study is aimed to investigate the methylation levels of the chromosome 11p15.5 region and metabolic problems in children with syndromic and nonsyndromic IUGR. Methylation analysis was performed for chromosome 11p15.5 in 49 patients (33 with suspected SRS and 16 nonsyndromic IUGR) with Netchine-Harbison clinical scoring (NHCS); uniparental disomy for chromosomes 6, 7, 14, and 20 was evaluated for those who were negative. LoM of ICR1 was detected in 14 of 33 suspected SRS patients with 3 or more criteria of NHCS, 5 had borderline LoM. Maternal uniparental disomy of the chromosomes 7 and 14 was found in 2 patients. The overall detection rate of SRS was 45.5%. While clinical findings were similar in patients with LoM and borderline LoM of ICR1, typical craniofacial findings were significantly less in the patients with normal methylation. Methylation patterns were not found to be impaired in the nonsyndromic IUGR group. Metabolic complications were evaluated in a total of 63 patients including 33 SRS-suspicious, 16 nonsyndromic IUGR, and 14 patients with 3M or SHORT syndrome. Increased rates of hypercalciuria, insulin resistance, and dyslipidemia were detected in patients with both syndromic and nonsyndromic IUGR. We would like to emphasize that detecting typical facial findings is effective in the diagnosis of SRS and paying attention to metabolic problems in the follow-up of patients with IUGR is recommended.

【 授权许可】

CC BY