title: Distinct phenotype of PHF6 deletions in females.
abstract: We report on two female patients carrying small overlapping Xq26.2 deletions of 100 kb and 270 kb involving the PHF6 gene. Mutations in PHF6 have been reported in individuals with Borjeson-Forssman-Lehmann syndrome, a condition present almost exclusively in males. Two very recent papers revealed de novo PHF6 defects in seven female patients with intellectual disability and a phenotype resembling Coffin-Siris syndrome (sparse hair, bitemporal narrowing, arched eyebrows, synophrys, high nasal root, bulbous nasal tip, marked clinodactyly with the hypoplastic terminal phalanges of the fifth fingers and cutaneous syndactyly of the toes, Blaschkoid linear skin hyperpigmentation, dental anomalies and occasional major malformations). The clinical presentation of these patients overlaps completely with our first patient, who carries a germline deletion involving PHF6. The second patient has a mosaic deletion and presented with a very mild phenotype of PHF6 loss in females. Our report confirms that PHF6 loss in females results in a recognizable phenotype overlapping with Coffin-Siris syndrome and distinct from Borjeson-Forssman-Lehmann syndrome. We expand the clinical spectrum and provide the first summary of the recommended medical evaluation.
authors.affiliation: Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Electronic address: nataliya.didonato@uniklinikum-dresden.de.
authors.forename: N
authors.initials: N
authors.lastname: Di Donato
authors.affiliation: CHU Nantes, Service de Genetique Medicale, Nantes, France.
authors.forename: B
authors.initials: B
authors.lastname: Isidor
authors.affiliation: Faculté de Chirurgie Dentaire, Département d'Odontologie Pédiatrique et CHU Nantes, Service d'Odontologie Conservatrice et Pédiatrique, Nantes, France.
authors.forename: S
authors.initials: S
authors.lastname: Lopez Cazaux
authors.affiliation: CHU Nantes, Service de Genetique Medicale, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Le Caignec
authors.affiliation: Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Klink
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kraus
authors.affiliation: Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schrock
authors.affiliation: Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Hackmann
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis; D002352:Carrier Proteins / Q000235:genetics*; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics*; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D004827:Epilepsy / Q000175:diagnosis; D005145:Face / Q000002:abnormalities; D019066:Facies; D005260:Female; D005385:Fingers / Q000002:abnormalities; D017353:Gene Deletion; D006130:Growth Disorders / Q000175:diagnosis; D006228:Hand Deformities, Congenital / Q000175:diagnosis; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis; D038901:X-Linked Intellectual Disability / Q000175:diagnosis; D008844:Micrognathism / Q000175:diagnosis; D009333:Neck / Q000002:abnormalities; D009765:Obesity / Q000175:diagnosis; D010641:Phenotype; D012097:Repressor Proteins; D049951:X Chromosome Inactivation
chemical_list: D002352:Carrier Proteins; C502542:PHF6 protein, human; D012097:Repressor Proteins
keywords: Borjeson–Forssman–Lehmann syndrome; Coffin–Siris syndrome; Microdeletion Xq26; PHF6 gene