F. Malvestiti1, C. Izzi2, B. Grimi1, B. Malvestiti1, L. Martinoni1, S. Paganini1, L. Marcato1, E. Baldi1, N. Palai2, F. Maggi1, G. Simoni1, F. R. Grati1
1Research and Development, Cytogenetics and Molecular Biology, TOMA Advanced Biomedical Assays, Busto Arsizio, Italy
2Prenatal Diagnosis Unit, Department of Obstetrics and Gynaecology, University of Brescia, Brescia, Italy.
ESGH 2014, Milano 31 Maggio- 3 Giugno
Abstract: Genomic rearrangements of 8q distal bands have been associated with several clinical entities, such as Langer-Giedion Syndrome. We report a unique familial case with complementary chromosomal aberrations involving the same distal 8q region, detected on fetus (deletion) and mother (mosaic duplication). Chromosome analysis on chorionic villi at 13 weeks of gestation for increased Down Syndrome risk after maternal serum screening revealed 46,XX,del(8)(q?23q?24.2) karyotype. The 8q deletion was defined as interstitial by subtelomeric and painting specific FISH probes. The deletion size was investigated by microarray and parental karyotype was performed. Microarray result was arr[hg19] 8q24.11q24.3(119,142,459-144,825,972)x1 with a 25 Mb deletion. The involved region included 74 OMIM genes and no recurrent microdeletion syndromes. Maternal karyotype was mos 46,XX,dup(8)(q?24.1q?24.3)[22]/46,XX[28]; the mosaic interstitial duplication was confirmed also by FISH and microarray, which disclosed the same fetal breakpoints. Only two cases have been described with pure 8q24 duplication characterized by microarray (Concolino et al., 2012;Wheeler, 2010) and none in mosaic condition. Mother had hydrocephalus at birth, short stature, facial dismorphisms, psychomotor and mild cognitive delay. Fetal ultrasound investigation was normal. Similar deletions have never been reported. We speculated about possible clinical consequences evaluating the role of genes mapped in the deleted/duplicated region, such as KCNK9, associated with Birk-Barel mental retardation dysmorphism sindrome (#612292); in brain tissues, it is expressed only from maternal allele and this might have a possible role in maternal and newborn phenotype. We have also suggested a possible mechanism of formation of this unique familial case.
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