| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Lapunzina, Pablo Mansilla, Elena Nevado, Julián Kutkowska-Kazmierczak, Anna Martinez-Glez, Victor Martínez-Fernández, María Luisa Hennekam, Raoul C. M. García-Miñaur, Sixto Obersztyn, Ewa Bocian, Ewa Simarro, Fernando Santos Bermejo, Eva Martínez-Frías, María Luisa Delicado, Alicia de Torres, María Luisa Ruiz-Perez, Victor L. Vallespín, Elena Fernandez, Luis Thuresson, Ann-Charlotte Lynch, Sally Ann Belligni, Elga F. Sharkey, Freddie H. Annerén, Göran Nowakowska, Beata Palomares, María |
| Description |
Country affiliation: Spain Author Affiliation: Palomares M ( 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) |
| 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. |
| ISSN |
00029297 |
| e-ISSN |
15376605 |
| DOI |
10.1016/j.ajhg.2011.06.012 |
| Journal |
The American Journal of Human Genetics |
| Issue Number |
2 |
| Volume Number |
89 |
| Language |
English |
| Publisher |
Cell Press (on behalf of American Society of Human Genetics) |
| Publisher Date |
2011-08-12 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Chromosome Deletion Chromosomes, Human, Pair 8 Genetics Intellectual Disability Adolescent Child, Preschool Comparative Genomic Hybridization Facies In Situ Hybridization, Fluorescence Phenotype Reproducibility Of Results Syndrome Research Support, Non-u.s. Gov't Discipline Human Genetics |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Genetics Genetics (clinical) |
