title: A MID1 gene mutation in a patient with Opitz G/BBB syndrome that altered the 3D structure of SPRY domain.
abstract: Mutations in the MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder that affects development of midline structures and comprises hypertelorism, cleft lip/palate, hypospadias, and laryngo-tracheo-esophageal abnormalities, and, at times, neurological, anal, and cardiac defects. MID1 gene abnormalities include missense, nonsense, and splicing mutations, small insertions, small deletions, and complex rearrangements. Here, we present a patient with Opitz G/BBB syndrome and a unique MID1 gene point mutation c.1703T<C (p. Ile568Thr) in exon 10. This mutation was located in the loop between β5 and β6 beta pleated sheets in the SPRY domain. According to our 3D models based on the PRY-SPRY domain of the human TRIM72, the I568T mutation altered the conformation in the loops between β5 and β6 and between β7 and β8. Thus, the I568T mutation altered the conformation of surface B of the binding pocket and may affect the binding affinity to the PRY domain.
authors.affiliation: Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Ching-Hsuan
authors.initials: CH
authors.lastname: Hu
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Liu
authors.forename: Ju-Shan
authors.initials: JS
authors.lastname: Yu
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Ng
authors.forename: Suh-Jen
authors.initials: SJ
authors.lastname: Chen
authors.forename: Pen-Hua
authors.initials: PH
authors.lastname: Su
authors.forename: Jia-Yuh
authors.initials: JY
authors.lastname: Chen
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D025063:Chromosome Disorders / Q000235:genetics; D004947:Esophagus / Q000002:abnormalities; D006801:Humans; D006972:Hypertelorism / Q000235:genetics*; D007021:Hypospadias / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D008868:Microtubule Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D008868:Microtubule Proteins; D009687:Nuclear Proteins; C558399:TRIM72 protein, human; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C109052:MID1 protein, human; D044767:Ubiquitin-Protein Ligases