title: Developmental delay referrals and the roles of Fragile X testing and molecular karyotyping: a New Zealand perspective.
abstract: 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.
authors.affiliation: Diagnostic Genetics, LabPlus, Auckland City Hospital, and School of Biological Sciences, University of Auckland, Auckland 1148, New Zealand.
authors.forename: Elaine
authors.initials: E
authors.lastname: Doherty
authors.forename: Rachel
authors.initials: R
authors.lastname: O'Connor
authors.forename: Anna
authors.initials: A
authors.lastname: Zhang
authors.forename: Christina
authors.initials: C
authors.lastname: Lim
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Love
authors.forename: Fern
authors.initials: F
authors.lastname: Ashton
authors.forename: Karen
authors.initials: K
authors.lastname: Claxton
authors.forename: Nerine
authors.initials: N
authors.lastname: Gregersen
authors.forename: Alice M
authors.initials: AM
authors.lastname: George
authors.forename: Donald R
authors.initials: DR
authors.lastname: Love
mesh_terms: D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000235:genetics*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000175:diagnosis*; D005820:Genetic Testing; D006801:Humans; D007621:Karyotyping / Q000379:methods*; D008297:Male; D009154:Mutation / Q000235:genetics; D009520:New Zealand; D012017:Referral and Consultation
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1