title: Targeted array comparative genomic hybridization--a new diagnostic tool for the detection of large copy number variations in nemaline myopathy-causing genes.
abstract: Nemaline myopathy (NM) constitutes a heterogeneous group of congenital myopathies. Mutations in the nebulin gene (NEB) are the main cause of recessively inherited NM. NEB is one of the most largest genes in human. To date, 68 NEB mutations, mainly small deletions or point mutations have been published. The only large mutation characterized is the 2.5 kb deletion of exon 55 in the Ashkenazi Jewish population. To investigate any copy number variations in this enormous gene, we designed a novel custom comparative genomic hybridization microarray, NM-CGH, targeted towards the seven known genes causative for NM. During the validation of the NM-CGH array we identified two novel deletions in two different families. The first is the largest deletion characterized in NEB to date, (∼53 kb) encompassing 24 exons. The second deletion (1 kb) covers two exons. In both families, the copy number change was the second mutation to be characterized and shown to have been inherited from one of the healthy carrier parents. In addition to these novel mutations, copy number variation was identified in four samples in three families in the triplicate region of NEB. We conclude that this method appears promising for the detection of copy number variations in NEB.
authors.affiliation: The Folkhälsan Institute of Genetics and the Department of Medical Genetics, University of Helsinki, Haartman Institute, Helsinki, Finland. kirsi.kiiski@helsinki.fi
authors.forename: K
authors.initials: K
authors.lastname: Kiiski
authors.forename: L
authors.initials: L
authors.lastname: Laari
authors.forename: V-L
authors.initials: VL
authors.lastname: Lehtokari
authors.forename: M
authors.initials: M
authors.lastname: Lunkka-Hytönen
authors.forename: C
authors.initials: C
authors.lastname: Angelini
authors.forename: R
authors.initials: R
authors.lastname: Petty
authors.forename: P
authors.initials: P
authors.lastname: Hackman
authors.forename: C
authors.initials: C
authors.lastname: Wallgren-Pettersson
authors.forename: K
authors.initials: K
authors.lastname: Pelin
mesh_terms: D016022:Case-Control Studies; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005387:Finland; D017353:Gene Deletion; D006801:Humans; D007585:Jews / Q000208:ethnology / Q000235:genetics; D008297:Male; D046228:Microarray Analysis; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D017696:Myopathies, Nemaline / Q000208:ethnology / Q000235:genetics*
chemical_list: D009124:Muscle Proteins; C035620:nebulin