title: HUWE1 mutations in Juberg-Marsidi and Brooks syndromes: the results of an X-chromosome exome sequencing study.
abstract: BACKGROUND
  X linked intellectual disability (XLID) syndromes account for a substantial number of males with ID. Much progress has been made in identifying the genetic cause in many of the syndromes described 20-40 years ago. Next generation sequencing (NGS) has contributed to the rapid discovery of XLID genes and identifying novel mutations in known XLID genes for many of these syndromes.
  
  
  METHODS
  2 NGS approaches were employed to identify mutations in X linked genes in families with XLID disorders. 1 involved exome sequencing of genes on the X chromosome using the Agilent SureSelect Human X Chromosome Kit. The second approach was to conduct targeted NGS sequencing of 90 known XLID genes.
  
  
  RESULTS
  We identified the same mutation, a c.12928 G>C transversion in the HUWE1 gene, which gives rise to a p.G4310R missense mutation in 2 XLID disorders: Juberg-Marsidi syndrome (JMS) and Brooks syndrome. Although the original families with these disorders were considered separate entities, they indeed overlap clinically. A third family was also found to have a novel HUWE1 mutation.
  
  
  CONCLUSIONS
  As we identified a HUWE1 mutation in an affected male from the original family reported by Juberg and Marsidi, it is evident the syndrome does not result from a mutation in ATRX as reported in the literature. Additionally, our data indicate that JMS and Brooks syndromes are allelic having the same HUWE1 mutation.
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Friez
authors.affiliation: Department of Pediatrics, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
authors.forename: Susan Sklower
authors.initials: SS
authors.lastname: Brooks
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Roger E
authors.initials: RE
authors.lastname: Stevenson
authors.affiliation: Hunter Genetics, Waratah, New South Wales, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Field
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Basehore
authors.affiliation: Institute of Endocrinology and Diabetes, The Children's Hospital of Westmead, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Lesley C
authors.initials: LC
authors.lastname: Adès
authors.affiliation: University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Sebold
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: McGee
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Saxon
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Skinner
authors.affiliation: Institute of Endocrinology and Diabetes, The Children's Hospital of Westmead, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Craig
authors.affiliation: Hunter Genetics, Waratah, New South Wales, Australia.
authors.forename: Lucy
authors.initials: L
authors.lastname: Murray
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Simensen
authors.affiliation: Department of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Ying Yzu
authors.initials: YY
authors.lastname: Yap
authors.affiliation: Department of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Shaw
authors.affiliation: Department of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Alison
authors.initials: A
authors.lastname: Gardner
authors.affiliation: Department of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Corbett
authors.affiliation: Department of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Raman
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bosshard
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: van Loon
authors.affiliation: Wellcome Sanger Trust Institute, Cambridge, UK.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Tarpey
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Fatima
authors.initials: F
authors.lastname: Abidi
authors.affiliation: Department of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Gecz
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D059472:Exome; D019066:Facies; D040181:Genetic Diseases, X-Linked; D006130:Growth Disorders / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D008607:Intellectual Disability; D008297:Male; D058627:Megalencephaly; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D008875:Middle Aged; D009128:Muscle Spasticity / Q000235:genetics*; D009154:Mutation; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D055815:Young Adult
chemical_list: D025521:Tumor Suppressor Proteins; C502830:HUWE1 protein, human; D044767:Ubiquitin-Protein Ligases