title: MID1 mutation screening in a large cohort of Opitz G/BBB syndrome patients: twenty-nine novel mutations identified.
abstract: Opitz G/BBB Syndrome (OS) is a multiple congenital anomaly disorder characterized by defects along the body midline. The disease is characterized by variable expressivity of signs that include hypertelorism, cleft lip and/or palate, laryngo-tracheo-esophageal abnormalities, cardiac defects, and hypospadias. OS patients also present with mental retardation and brain anatomical abnormalities. An autosomal dominant form mapping to chromosome 22 and an X-linked form of OS are known. The gene responsible for the X-linked form of OS, MID1, codes for a member of the Tripartite Motif family of E3 ubiquitin ligases. Here we report 29 novel mutations in 29 unrelated patients of a cohort of 140 male OS cases. These mutations are found in both familial and sporadic cases. They are scattered along the entire length of the gene and are represented by missense and nonsense mutations, insertions and deletions causing frame shift mutations, and deletion of either single exons or the entire gene. The variety of the mutations found confirms that loss-of-function is the mechanism underlying the OS phenotype. Moreover, the low percentage of MID1-mutated OS patients, 47% of the familial and 13% of the sporadic cases, suggests a wider genetic heterogeneity underlying the OS phenotype.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Ferrentino
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bassi
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Tabolacci
authors.forename: Germana
authors.initials: G
authors.lastname: Meroni
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008868:Microtubule Proteins / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
chemical_list: D008868:Microtubule Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C109052:MID1 protein, human; D044767:Ubiquitin-Protein Ligases