Craniofacial abnormalities and developmental delay in two families with overlapping 22q12.1 microdeletions involving the MN1 gene. Am J Med Genet A 2015 May;167A(5):1047-53
Date
03/27/2015Pubmed ID
25810350DOI
10.1002/ajmg.a.36839Scopus ID
2-s2.0-84927737330 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
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.
Author List
Beck M, Peterson JF, McConnell J, McGuire M, Asato M, Losee JE, Surti U, Madan-Khetarpal S, Rajkovic A, Yatsenko SAMESH terms used to index this publication - Major topics in bold
AdultAnimals
Child, Preschool
Chromosome Deletion
Chromosomes, Human, Pair 22
Cleft Palate
Craniofacial Abnormalities
Developmental Disabilities
Female
Humans
Infant
Male
Mice
Neurofibromin 2
Pedigree
Trans-Activators
Tumor Suppressor Proteins
