title: Mutations in SPECC1L, encoding sperm antigen with calponin homology and coiled-coil domains 1-like, are found in some cases of autosomal dominant Opitz G/BBB syndrome.
abstract: BACKGROUND
  Opitz G/BBB syndrome is a heterogeneous disorder characterised by variable expression of midline defects including cleft lip and palate, hypertelorism, laryngealtracheoesophageal anomalies, congenital heart defects, and hypospadias. The X-linked form of the condition has been associated with mutations in the MID1 gene on Xp22. The autosomal dominant form has been linked to chromosome 22q11.2, although the causative gene has yet to be elucidated.
  
  
  RESULTS
  In this study, we performed whole exome sequencing on DNA samples from a three-generation family with characteristics of Opitz G/BBB syndrome with negative MID1 sequencing. We identified a heterozygous missense mutation c.1189A>C (p.Thr397Pro) in SPECC1L, located at chromosome 22q11.23. Mutation screening of an additional 19 patients with features of autosomal dominant Opitz G/BBB syndrome identified a c.3247G>A (p.Gly1083Ser) mutation segregating with the phenotype in another three-generation family.
  
  
  CONCLUSIONS
  Previously, SPECC1L was shown to be required for proper facial morphogenesis with disruptions identified in two patients with oblique facial clefts. Collectively, these data demonstrate that SPECC1L mutations can cause syndromic forms of facial clefting including some cases of autosomal dominant Opitz G/BBB syndrome and support the original linkage to chromosome 22q11.2.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Kruszka
authors.affiliation: The Center for Applied Genomics, The Children's Hospital of Philadelphia, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Harr
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Wilson
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Swarr
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: McCormick
authors.affiliation: The Center for Applied Genomics, The Children's Hospital of Philadelphia, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Rosetta M
authors.initials: RM
authors.lastname: Chiavacci
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Mindy
authors.initials: M
authors.lastname: Li
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ariel F
authors.initials: AF
authors.lastname: Martinez
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Hart
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: McDonald-McGinn
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Deardorff
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Marni J
authors.initials: MJ
authors.lastname: Falk
authors.affiliation: Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Allanson
authors.affiliation: Shodair Children's Hospital, Helena, Montana, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Hudson
authors.affiliation: Shodair Children's Hospital, Helena, Montana, USA Clinical Genetics and Metabolism, Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Johnson
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Irfan
authors.initials: I
authors.lastname: Saadi
authors.affiliation: The Center for Applied Genomics, The Children's Hospital of Philadelphia, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
mesh_terms: D000328:Adult; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D004252:DNA Mutational Analysis; D004947:Esophagus / Q000002:abnormalities*; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D006972:Hypertelorism / Q000235:genetics*; D007021:Hypospadias / Q000235:genetics*; D007223:Infant; D008297:Male; D008840:Microfilament Proteins / Q000737:chemistry*; D008868:Microtubule Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics; D044767:Ubiquitin-Protein Ligases; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D008868:Microtubule Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D000096985:Calponins; C558855:SPECC1L protein, human; C109052:MID1 protein, human
keywords: Clinical genetics; Developmental; Diagnosis; Genetics