title: Characterization of a 8q21.11 microdeletion syndrome associated with intellectual disability and a recognizable phenotype.
abstract: We report eight unrelated individuals with intellectual disability and overlapping submicroscopic deletions of 8q21.11 (0.66-13.55 Mb in size). The deletion was familial in one and simplex in seven individuals. The phenotype was remarkably similar and consisted of a round face with full cheeks, a high forehead, ptosis, cornea opacities, an underdeveloped alae, a short philtrum, a cupid's bow of the upper lip, down-turned corners of the mouth, micrognathia, low-set and prominent ears, and mild finger and toe anomalies (camptodactyly, syndactyly, and broadening of the first rays). Intellectual disability, hypotonia, decreased balance, sensorineural hearing loss, and unusual behavior were frequently observed. A high-resolution oligonucleotide array showed different proximal and distal breakpoints in all of the individuals. Sequencing studies in three of the individuals revealed that proximal and distal breakpoints were located in unique sequences with no apparent homology. The smallest region of overlap was a 539.7 kb interval encompassing three genes: a Zinc Finger Homeobox 4 (ZFHX4), one microRNA of unknown function, and one nonfunctional pseudogen. ZFHX4 encodes a transcription factor expressed in the adult human brain, skeletal muscle, and liver. It has been suggested as a candidate gene for congenital bilateral isolated ptosis. Our results suggest that the 8q21.11 submicroscopic deletion represents a clinically recognizable entity and that a haploinsufficient gene or genes within the minimal deletion region could underlie this syndrome.
authors.affiliation: Section of Functional and Structural Genomics, Instituto de Genética Médica y Molecular (INGEMM), Instituto de Investigación Sanitaria (IdiPAZ), Hospital Universitario La Paz, Madrid, Spain. mpalomares.hulp@salud.madrid.org
authors.forename: María
authors.initials: M
authors.lastname: Palomares
authors.forename: Alicia
authors.initials: A
authors.lastname: Delicado
authors.forename: Elena
authors.initials: E
authors.lastname: Mansilla
authors.forename: María Luisa
authors.initials: ML
authors.lastname: de Torres
authors.forename: Elena
authors.initials: E
authors.lastname: Vallespín
authors.forename: Luis
authors.initials: L
authors.lastname: Fernandez
authors.forename: Victor
authors.initials: V
authors.lastname: Martinez-Glez
authors.forename: Sixto
authors.initials: S
authors.lastname: García-Miñaur
authors.forename: Julián
authors.initials: J
authors.lastname: Nevado
authors.forename: Fernando Santos
authors.initials: FS
authors.lastname: Simarro
authors.forename: Victor L
authors.initials: VL
authors.lastname: Ruiz-Perez
authors.forename: Sally Ann
authors.initials: SA
authors.lastname: Lynch
authors.forename: Freddie H
authors.initials: FH
authors.lastname: Sharkey
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Thuresson
authors.forename: Göran
authors.initials: G
authors.lastname: Annerén
authors.forename: Elga F
authors.initials: EF
authors.lastname: Belligni
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martínez-Fernández
authors.forename: Eva
authors.initials: E
authors.lastname: Bermejo
authors.forename: Beata
authors.initials: B
authors.lastname: Nowakowska
authors.forename: Anna
authors.initials: A
authors.lastname: Kutkowska-Kazmierczak
authors.forename: Ewa
authors.initials: E
authors.lastname: Bocian
authors.forename: Ewa
authors.initials: E
authors.lastname: Obersztyn
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martínez-Frías
authors.forename: Raoul C M
authors.initials: RC
authors.lastname: Hennekam
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D019066:Facies; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010641:Phenotype; D015203:Reproducibility of Results; D013577:Syndrome