Complex rearrangement of the exon 6 genomic region among Opitz G/BBB Syndrome MID1 alterations

Chiara Migliore, Emmanouil Athanasakis, Sophie Dahoun, Ambroise Wonkam, Melissa Lees, Olga Calabrese, Fiona Connell, Sally Ann Lynch, Claudia Izzi, Eva Pompilii, Seema Thakur, Merel van Maarle, Louise C. Wilson, Germana Meroni

Research output: Contribution to journalArticlepeer-review

Abstract

Opitz G/BBB Syndrome (OS) is a multiple congenital anomaly disorder characterized by developmental defects of midline structures. The most relevant clinical signs are ocular hypertelorism, hypospadias, cleft lip and palate, laryngo-tracheo-esophageal abnormalities, imperforate anus, and cardiac defects. Developmental delay, intellectual disability and brain abnormalities are also present. The X-linked form of this disorder is caused by mutations in the MID1 gene coding for a member of the tripartite motif family of E3 ubiquitin ligases. Here, we describe 12 novel patients that carry MID1 mutations emphasizing that laryngo-tracheo-esophageal defects are very common in OS patients and, together with hypertelorism and hypospadias, are the most frequent findings among the full spectrum of OS clinical manifestations. Besides missense and nonsense mutations, small insertions and deletions scattered along the entire length of the gene, we found that a consistent number of MID1 alterations are represented by the deletion of single coding exons. Deep characterization of one of these deletions reveals, for the first time within the MID1 gene, a complex rearrangement composed of two deletions, an inversion and a small insertion that may suggest the involvement of concurrent non-homologous mechanisms in the generation of the observed structural variant.

Original languageEnglish
Pages (from-to)404-410
Number of pages7
JournalEuropean Journal of Medical Genetics
Volume56
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • MID1
  • Midline defects
  • Opitz G/BBB Syndrome
  • Structural variants
  • X-chromosome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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