title: Hypospadias associated with hypertelorism, the mildest phenotype of Opitz syndrome.
abstract: Hypospadias is a common congenital malformation in boys in which the urethral meatus opens on the underside of the penis. It is considered a complex disorder with several genes involved and the molecular etiology is just beginning to be revealed. As more than 85% of Opitz G/BBB syndrome (OS) patients with MID1 mutations are manifested with hypospadias, we have investigated the association between the MID1 gene and hypospadias. DNA from 114 hypospadias cases was analyzed with direct sequencing of the MID1 gene. Genotyping analysis was performed for the single-nucleotide polymorphism (SNP) c.1230G>A in 370 individuals with varying degrees of hypospadias and compared with 759 healthy controls. We identified one nonsense mutation c.712G>T (p.E238X), one missense mutation c.1679A>G (p.K560R) and two synonymous variants c.1230G>A (p.S410S) and c.1284T>G (p.V428V). We also detected a significant difference in the rare allele frequency of SNP c.1230G>A in hypospadias patients as compared with controls (P=0.016). Our finding suggests that hypospadias associated with hypertelorism is the mildest phenotype in OS caused by MID1 mutations.
authors.affiliation: Department of Urology, The Second Hospital, Shandong University, Jinan, PR China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Yougen
authors.initials: Y
authors.lastname: Chen
authors.forename: Shentiang
authors.initials: S
authors.lastname: Zhao
authors.forename: Ellen
authors.initials: E
authors.lastname: Markljung
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordenskjöld
mesh_terms: D000595:Amino Acid Sequence; D016022:Case-Control Studies; D004947:Esophagus / Q000002:abnormalities / Q000473:pathology; D005091:Exons; D005260:Female; D006801:Humans; D006972:Hypertelorism / Q000235:genetics* / Q000473:pathology; D007021:Hypospadias / Q000235:genetics* / Q000473:pathology; D008297:Male; D008868:Microtubule Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016415:Sequence Alignment; 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