title: Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate.
abstract: Truncating mutations were found in the PHF8 gene (encoding the PHD finger protein 8) in two unrelated families with X linked mental retardation (XLMR) associated with cleft lip/palate (MIM 300263). Expression studies showed that this gene is ubiquitously transcribed, with strong expression of the mouse orthologue Phf8 in embryonic and adult brain structures. The coded PHF8 protein harbours two functional domains, a PHD finger and a JmjC (Jumonji-like C terminus) domain, implicating it in transcriptional regulation and chromatin remodelling. The association of XLMR and cleft lip/palate in these patients with mutations in PHF8 suggests an important function of PHF8 in midline formation and in the development of cognitive abilities, and links this gene to XLMR associated with cleft lip/palate. Further studies will explore the specific mechanisms whereby PHF8 alterations lead to mental retardation and midline defects.
authors.forename: F
authors.initials: F
authors.lastname: Laumonnier
authors.forename: S
authors.initials: S
authors.lastname: Holbert
authors.forename: N
authors.initials: N
authors.lastname: Ronce
authors.forename: F
authors.initials: F
authors.lastname: Faravelli
authors.forename: S
authors.initials: S
authors.lastname: Lenzner
authors.forename: C E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: J
authors.initials: J
authors.lastname: Lespinasse
authors.forename: H
authors.initials: H
authors.lastname: Van Esch
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.forename: C
authors.initials: C
authors.lastname: Goizet
authors.forename: F
authors.initials: F
authors.lastname: Phan-Dinh Tuy
authors.forename: H
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: J-P
authors.initials: JP
authors.lastname: Fryns
authors.forename: J
authors.initials: J
authors.lastname: Chelly
authors.forename: H-H
authors.initials: HH
authors.lastname: Ropers
authors.forename: C
authors.initials: C
authors.lastname: Moraine
authors.forename: B C J
authors.initials: BC
authors.lastname: Hamel
authors.forename: S
authors.initials: S
authors.lastname: Briault
mesh_terms: D000818:Animals; D041321:Chromosomes, Human, X; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D056466:Histone Demethylases; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors; D056466:Histone Demethylases; C511934:PHF8 protein, human