Molecular cytogenetics in the diagnosis of mental retardation in Malta

Abstract

Molecular cytogenetics can detect genomic imbalance which is not visible using conventional cytogenetics. In this study a total of 300 individuals with mental retardation were studied to establish the validity of molecular cytogenetics within a clinical diagnostic protocol. Screening for cryptic rearrangements was done in a total of 73 families using subtelomeric probes and 15 of these who proved negative were studied using array CGH. Array CGH was also used to study two cases with supernumerary marker chromosomes, a de novo translocation involving 3p and Xp and two males with a history of specific XLMR. Molecular cytogenetics was capable of identifying 6 rearrangements: a micro deletion of chromosome 15q11-13, a micro deletion of chromosome 1pter, a cryptic translocation between chromosome 7p and 9p in two individuals, a 2Nffi duplication of chromosome 11q25, a 6MB deletion of chromosome 22q12. The diagnostic yield using molecular cytogenetics was comparable to that of routine karyotyping (7/300) and testing for FMRl gene (7/300). Four case studies which highlight the importance of dysmorphology and cryptic genomic imbalances in mental retardation are presented. These are a case with three SMCs from chromosome 5, a case with a partial trisomy of chromosome 21, a case with features of Toriello-Carey syndrome and a 6MB deletion at 22q12 and a family of three sisters with features of Cohen syndrome and ovarian dysgenesis. Using the results of this study a protocol is proposed for the use of molecular cytogenetics within a diagnostic protocol for mental retardation in Malta.