Inverted duplication of 15q with terminal deletion in a multiple malformed newborn with intrauterine growth failure and lethal phenotype

Abstract

We describe the cytogenetic and molecular characterization of an inverted duplication of chromosome 15q with evidence of a terminal deletion of the same rearranged chromosome. The proband was a multiple congenital malformed female with a prenatal diagnosis of trisomy 15q and an extremely severe clinical course. The phenotype of the patient was characterized by marked intrauterine growth retardation, congenital heart defect, "horseshoe" kidney, hand contractures, and clubfeet. The exitus came at 20 days because of progressive cardio-respiratory impairment. Overall, the clinical phenotype appeared more severe than usual trisomy 15q syndrome. Postnatal cytogenetic and molecular studies unraveled a "de novo" inverted duplication of 15q (q21.3-->q26.3), associated with the deletion of the 15q telomere and part of the band 15q26.3. A single copy region spanning approximately 600 kb between the duplicated segments was present. Correlation between the clinical findings of the patient and the phenotype of trisomy 15q reported in literature is also provided.

Chromosome 15 structural abnormalities: effect on IGF1R gene expression and function

“…To the best of our knowledge, up to now, 96 patients with chromosome 15q duplication have been reported in literature. Among these, 28 patients showed distal 15q tetrasomy due to a mosaicism or to a neocentromer marker chromosome (NMC) ( 2 , 3 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ) and the others had 15q distal trisomy ( 1 , 2 , 3 , 4 , 5 , 8 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ). The duplication of 15q chromosome can be classified in pure and impure forms, based on the presence of another chromosome abnormality (e.g.…”

“…This structural chromosomal abnormality causes a common phenotype that includes prenatal and postnatal overgrowth, intellectual disability, characteristic craniofacial dimorphism and renal abnormalities ( 3 ), resulting in the so-called 15q overgrowth syndrome. However, failure to thrive and/or intrauterine growth retardation (IUGR) have been reported in some patients with chromosome 15q terminal duplication ( 2 , 4 , 5 ), thus suggesting that triplication of the IGF1R gene does not seem to be sufficient to cause somatic overgrowth.…”

A case of de novo duplication of 15q24-q26.3

“…In the majority of patients, duplication of 15q is concomitant with translocation or deletion. Breakpoints in distal 15q trisomy occur most often between bands 15q21 and 15q235,6). Van Allen et al7) reported on families with breakpoints at 15q15 and 15q26, respectively.…”

“…The second chromosome involved in the reciprocal translocation has varied; chromosomes 2, 7, 8, 11, 13, 15 (Robertsonian translocation), and 21 have been reported6). Other cases of 15q duplication have been the result of direct or inverted duplication14,15).…”

Trisomy Xp and partial tetrasomy Xq resulting from gain of a rearranged X chromosome in a female fetus: pathogenic or not?

“…Several mechanisms have been reported for the formation of inverted duplication with terminal deletion [ 3 – 7 ]. In this present case, an illegitimate crossing-over event took place between two maternal X homologous chromosomes at Xq22.1.…”