Is autosomal recessive Silver-Russel syndrome a separate entity or is it part of the 3-M syndrome spectrum?

Nadia A. Akawi, Bassam R. Ali, Hanan Hamamy, Azmy Al-Hadidy, Lihadh Al-Gazali

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Intrauterine growth retardation (IUGR) is a nonspecific finding that occurs in approximately 0.17% of all live-births. However, IUGR can also be a significant feature of many recognized genetic syndromes including Silver-Russel syndrome (SRS), Three M syndrome (3-M), Dubowitz syndrome, and Mulibrey nanism. Differentiation of 3-M syndrome from autosomal recessive SRS has been difficult because of the phenotypic variability of the latter. Limb length asymmetry is seen in over half of those with autosomal recessive SRS, but not in individuals with 3-M syndrome. Characteristic radiologic findings of 3-M syndrome are not present in SRS. We used single nucleotide polymorphism (SNP) microarrays to investigate the cause of phenotypic features of SRS that shows autosomal recessive inheritance in three consanguineous families, two from United Arab Emirates (UAE), and one from Jordan. The mapped regions contained CUL7 and OBSL1, the genes that have recently been shown to cause 3-M syndrome. Subsequently, direct DNA sequencing of CUL7 and OBSL1 genes revealed novel mutations in both genes including two mutations in OBSL1 [c.1119G>C (p.W373C) and c.681-682delinsTT (p.Q228X)], and a nonsense mutation in CUL7 [c.203G>A (p.W68X)]. In addition, a six nucleotide deletion in CUL7 [c.649-654delAGCCGC (p.217-218delSR)] was found in a consanguineous family from UAE that had the typical features of 3-M. As a result of these findings, we question the identity of the autosomal recessive SRS and suggest that all apparently recessive SRS families should be tested for mutations in CUL7 and OBSL1.

Original languageEnglish
Pages (from-to)1236-1245
Number of pages10
JournalAmerican Journal of Medical Genetics, Part A
Volume155
Issue number6
DOIs
Publication statusPublished - Jun 2011

Keywords

  • CUL7
  • OBSL1
  • Silver-Russel syndrome
  • Three M syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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