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Developmental delay referrals and the roles of Fragile X testing and molecular karyotyping: A New Zealand perspective

2013; Spandidos Publishing; Volume: 7; Issue: 5 Linguagem: Inglês

10.3892/mmr.2013.1386

1791-3004

Elaine Eggleston Doherty, Rachel O’Connor, Anna Zhang, Christina Lim, Jennifer M. Love, Fern Ashton, Karen Claxton, Nerine Gregersen, Alice M. George, Donald R. Love,

Congenital heart defects research

Global developmental delay (GDD) affects ~1-3% of children, many of whom will also have intellectual disability (ID). Fragile X is the major genetic cause of GDD with mental retardation (MR) in males, accounting for ~20% of all X-linked MR. As Fragile X has serious genetic implications, the overwhelming majority of developmental delay (DD) cases referred to our laboratory are concerned with the exclusion of a diagnosis of Fragile X, along with simultaneous karyotype analysis to confirm chromosome aberrations. Critically, molecular laboratories have generally experienced a falling positive detection frequency of Fragile X. In this context, the recent implementation of array‑based techno-logy has significantly increased the likelihood of detecting chromosome aberrations that underpin DD. In the current study, we report a Fragile X mutation detection frequency for DD referrals that is comparable with the falling UK detection frequencies. In addition, we find that there is a 9‑fold greater likelihood of detecting clinically significant chromosomal aberrations than of detecting a full Fragile X mental retardation 1 (FMR1) gene CGG repeat expansion in cases referred on the basis of DD. We propose a more efficent sequential testing algorithm that involves an initial molecular karyotype, cascading to FMR1 gene analysis in the event of a negative result.