Louise Korte1, Sarah Higgins1, Jillian Nicholl1, Alison Attwood1, Ryan Storer1, Sarah Smith1, Yvonne Hull1, Sue Brown1, Rhonda Hutchinson1, Christopher Barnett2, Jan Liebelt2
1SA Pathology, Cytogenetics Unit, Department of Genetic Medicine, WCH, 72 King William Road, North Adelaide, SA, 5006
2SA Clinical Genetics Services, WCH, 72 King William Road, North Adelaide, SA, 5006
Microarray technology is now widely used to diagnose pathogenic copy number variants (CNVs) in neurological disorders (Intellectual disability, autism, schizophrenia etc.). We routinely ask for parental follow up to determine if changes are inherited or de novo and to clarify the clinical significance of the majority of CNVs we detect. We will present four cases where SNP array has identified a CNV in the proband and parental follow up has shown mosaicism. This significantly increases the possibility of recurrence of another similarly affected child. Three of these inherited changes were not detectable by routine cytogenetic analysis. This illustrates the value of FISH investigation for parental follow up.
Case 1: An additional supernumerary bisatellited chromosome 22 marker was detected, consistent with a diagnosis of Cat Eye Syndrome. Family studies showed the marker chromosome 22 was maternally inherited, present in 67% of metaphases examined.
Case 2: A 2Mb deletion of chromosome 17p11.2 involving the RAI1 gene was detected, consistent with a diagnosis of Smith-Magenis syndrome. The deletion was maternally inherited, present in 64% of cells examined.
Case 3: 4.2Mb duplication at chromosome 1q43-q44 involving the AKT3 gene was detected. A low level of mosaicism was detected in the mother, however FISH results fell outside the reporting guidelines. A Masked array showed a slight divergence of the B allele frequency, which supports this FISH result.
Case 4: A 560kb deletion of chromosome 2p16.3, involving the NRNX1 gene was detected. The deletion was maternally inherited, present in approximately 30% of cells examined.
Cytogenetics laboratory at the women’s and children’s hospital