title: Complex rearrangement of the exon 6 genomic region among Opitz G/BBB Syndrome MID1 alterations.
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.
authors.affiliation: Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Migliore
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Athanasakis
authors.forename: Sophie
authors.initials: S
authors.lastname: Dahoun
authors.forename: Ambroise
authors.initials: A
authors.lastname: Wonkam
authors.forename: Melissa
authors.initials: M
authors.lastname: Lees
authors.forename: Olga
authors.initials: O
authors.lastname: Calabrese
authors.forename: Fiona
authors.initials: F
authors.lastname: Connell
authors.forename: Sally Ann
authors.initials: SA
authors.lastname: Lynch
authors.forename: Claudia
authors.initials: C
authors.lastname: Izzi
authors.forename: Eva
authors.initials: E
authors.lastname: Pompilii
authors.forename: Seema
authors.initials: S
authors.lastname: Thakur
authors.forename: Merel
authors.initials: M
authors.lastname: van Maarle
authors.forename: Louise C
authors.initials: LC
authors.lastname: Wilson
authors.forename: Germana
authors.initials: G
authors.lastname: Meroni
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D007446:Chromosome Inversion; D002972:Cleft Palate / Q000235:genetics*; D004947:Esophagus / Q000002:abnormalities*; D005091:Exons; D023061:Gene Order; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D006972:Hypertelorism / Q000235:genetics*; D007021:Hypospadias / Q000235:genetics*; D007223:Infant; D008297:Male; D008868:Microtubule Proteins / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D044767:Ubiquitin-Protein Ligases; D055815:Young Adult
chemical_list: D008868:Microtubule Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C109052:MID1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: MID1; Midline defects; Opitz G/BBB Syndrome; Structural variants; X-chromosome