title: Craniofacial abnormalities and developmental delay in two families with overlapping 22q12.1 microdeletions involving the MN1 gene.
abstract: Deletions spanning the MN1 gene (22q12.1) have recently been proposed as playing a role in craniofacial abnormalities that include cleft palate, as mouse studies have demonstrated that Mn1 haploinsufficiency results in skull abnormalities and secondary cleft palate. We report on four patients (two families) with craniofacial abnormalities and intellectual disability with overlapping microdeletions that span the MN1 gene. Comparative genomic hybridization microarray analysis revealed a 2.76 Mb deletion in the 22q12.1 region, in three family members (Family 1), that contains the MN1 gene. In addition, a complex 22q12 rearrangement, including a 1.61 Mb deletion containing the MN1 gene and a 2.28 Mb deletion encompassing the NF2 gene, has been identified in another unrelated patient (Family 2). Based upon genotype-phenotype correlation among our patients and those previously reported with overlapping 22q12 deletions, we identified a 560 kb critical region containing the MN1 gene that is implicated in human cleft palate formation. Importantly, NF2 was also found within the 22q12 deletion region in several patients which enabled specific clinical management for neurofibromatosis 2.
authors: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Megan
authors: M
authors: Beck
authors: Jess F
authors: JF
authors: Peterson
authors: Juliann
authors: J
authors: McConnell
authors: Marianne
authors: M
authors: McGuire
authors: Miya
authors: M
authors: Asato
authors: Joseph E
authors: JE
authors: Losee
authors: Urvashi
authors: U
authors: Surti
authors: Suneeta
authors: S
authors: Madan-Khetarpal
authors: Aleksandar
authors: A
authors: Rajkovic
authors: Svetlana A
authors: SA
authors: Yatsenko
mesh_terms: D000328:Adult; D000818:Animals; D002675:Child, Preschool; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002972:Cleft Palate / Q000235:genetics* / Q000503:physiopathology; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000503:physiopathology; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D025581:Neurofibromin 2 / Q000235:genetics; D010375:Pedigree; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C506524:MN1 protein, human; D025581:Neurofibromin 2; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins
keywords: 22q12.1; 22q12.2-q12.3; CHEK2; MN1; NF2; array comparative genomic hybridization (aCGH); cleft palate; microdeletion; neurofibromatosis type 2