title: Respiratory failure, cleft palate and epilepsy in the mouse model of human Xq22.1 deletion syndrome.
abstract: Chromosomal segmental deletion is a frequent cause of human diseases. A familial 1.1 Mb deletion of human chromosome Xq22.1 associates with epilepsy, cleft palate and developmental defects in heterozygous female patients. Here, we describe a mouse mutant with a targeted deletion of the syntenic segment of the mouse X chromosome that phenocopies the human syndrome. Male mice with a deletion of a 1.1 Mb Nxf2-Nxf3 X-chromosomal segment exhibit respiratory failure, neonatal lethality and cleft palate. In female mice, heterozygosity for the deletion manifests cleft palate, early postnatal lethality, postnatal growth delay and spontaneous seizures in surviving animals, apparently due to X-chromosome inactivation. Furthermore, loss of a 0.35 Mb subregion containing Armcx5, Gprasp1, Gprasp2 and Bhlhb9 is sufficient to cause the Xq22.1 syndrome phenotype. Our results support that the 1.1 Mb deletion of human Xq22.1 is the genetic cause of the associated syndrome.
authors.affiliation: Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA and.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: The Children's Hospital of Philadelphia, Division of Neurology, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA 19104-4399, USA.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Goldberg
authors.affiliation: Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA and.
authors.forename: N Adrian
authors.initials: NA
authors.lastname: Leu
authors.affiliation: The Children's Hospital of Philadelphia, Division of Neurology, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA 19104-4399, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: The Children's Hospital of Philadelphia, Division of Neurology, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA 19104-4399, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Coulter
authors.affiliation: Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA and pwang@vet.upenn.edu.
authors.forename: P Jeremy
authors.initials: PJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002972:Cleft Palate / Q000235:genetics*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D005804:Genes, Lethal; D040181:Genetic Diseases, X-Linked / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D012131:Respiratory Insufficiency / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*