Array CGH and Conventional Karyotyping: the Description of Two Selected Cases

The aim of this work was to improve genetic diagnostics at the Children Hospital Joana de Gusmão in Florianópolis, Brazil. The use of the array CGH (aCGH) has aided significantly the genetic diagnosis in recent years. In our laboratory aCGH combined with conventional karyotyping allowed an improvement of 20% to 30% in the diagnostic rate of patients with intellectual disabillity, dysmorphisms, autism and developmental delay. We used the Affymetrix chip Cytoscan HD and 750 K Cytoscan arrays (Santa Clara, CA) and analysis through the respective software system and for conventional karyotype (G Banding). We selected 2 cases to report: Case 1: Two siblings with distinct developmental disturbance phenotypes. Sibling one is a 7-year-old female with severe developmental delay phenotype, microcephaly and consanguineous parents. She presented an interstitial deletion of 12,1 Mb on chromosome 5, arr [hg19] 5p14.3- p15.31 (6,801,589-18,992,827) ×1, featuring the Cri-du-chat syndrome. Her brother, a 12-year-old male with mild intellectual disability (ID) a duplication of the exact same size and region that was deleted in the sister was found arr [hg19] 5p14.3-p15.31 (6,801,589-18,992,827) ×3. Parental aCGH was normal. However, conventional karyotype of the father revealed 2 reciprocal translocation between chromosomes 1 and 2, 5 and 7: (46, XY, t(1, 2) (q44;∼ p23-pter) t(5; 7)(p14.3-p15.31; p22). Case 2: A 16-year-old female with consanguineous parents and normal conventional karyotyping. She presents significant developmental delay, dyslalia, severe ID, autistic traits, irritability, hyperactivity and autoagression, without obvious dysmorphias and with normal: MRI, electroencephalogram and CT scan results. Microarray analysis revealed a homozygous microdeletion of 197 Kbp on chromosome 8:arr [hg19] 8p22 (15,451,748-15,649,733) ×1, spanning almost the entire TUSC3 gene, except promoter and first exon (601385*).This is the seventh family with a reported TUSC3 mutation with mostly non syndromic ID and the second with the same deletion (Khan et al, 2011). Three of the families reported in the literature carried a deletion which encompassed only the TUSC3 promoter region and the first exon, 2 families presented distinct point mutations and 1 an intragenic duplication. All 7 families presented homozygous mutations, only 1 was not consanguineous however they were from the same village.