title: Mutations in the LHX2 gene are not a frequent cause of micro/anophthalmia.
abstract: OBJECTIVE
  Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. A few genes (orthodenticle homeobox 2 [OTX2], retina and anterior neural fold homeobox [RAX], SRY-box 2 [SOX2], CEH10 homeodomain-containing homolog [CHX10], and growth differentiation factor 6 [GDF6]) have been implicated mainly in isolated micro/anophthalmia but causative mutations of these genes explain less than a quarter of these developmental defects. The essential role of the LIM homeobox 2 (LHX2) transcription factor in early eye development has recently been documented. We postulated that mutations in this gene could lead to micro/anophthalmia, and thus performed molecular screening of its sequence in patients having micro/anophthalmia.
  
  
  METHODS
  Seventy patients having non-syndromic forms of colobomatous microphthalmia (n=25), isolated microphthalmia (n=18), or anophthalmia (n=17), and syndromic forms of micro/anophthalmia (n=10) were included in this study after negative molecular screening for OTX2, RAX, SOX2, and CHX10 mutations. Mutation screening of LHX2 was performed by direct sequencing of the coding sequences and intron/exon boundaries.
  
  
  RESULTS
  Two heterozygous variants of unknown significance (c.128C>G [p.Pro43Arg]; c.776C>A [p.Pro259Gln]) were identified in LHX2 among the 70 patients. These variations were not identified in a panel of 100 control patients of mixed origins. The variation c.776C>A (p.Pro259Gln) was considered as non pathogenic by in silico analysis, while the variation c.128C>G (p.Pro43Arg) considered as deleterious by in silico analysis and was inherited from the asymptomatic father.
  
  
  CONCLUSIONS
  Mutations in LHX2 do not represent a frequent cause of micro/anophthalmia.
authors.affiliation: INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
authors.forename: Annaïck
authors.initials: A
authors.lastname: Desmaison
authors.forename: Adeline
authors.initials: A
authors.lastname: Vigouroux
authors.forename: Claudine
authors.initials: C
authors.lastname: Rieubland
authors.forename: Christine
authors.initials: C
authors.lastname: Peres
authors.forename: Patrick
authors.initials: P
authors.lastname: Calvas
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
mesh_terms: D000595:Amino Acid Sequence; D000853:Anophthalmos / Q000235:genetics*; D001483:Base Sequence; D015331:Cohort Studies; D017124:Conserved Sequence / Q000235:genetics; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008850:Microphthalmos / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C489783:LHX2 protein, human; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors