Derivative chromosomes involving 5p large rearranged segments went unnoticed with the use of conventional cytogenetics

Abstract

BackgroundIn countries where comparative genomic hybridization arrays (aCGH) and next generation sequencing are not widely available due to accessibility and economic constraints, conventional 400–500-band karyotyping is the first-line choice for the etiological diagnosis of patients with congenital malformations and intellectual disability. Conventional karyotype analysis can rule out chromosomal alterations greater than 10 Mb. However, some large structural abnormalities, such as derivative chromosomes, may go undetected when the analysis is performed at less than a 550-band resolution and the size and banding pattern of the interchanged segments are similar. Derivatives frequently originate from inter-chromosomal exchanges and sometimes are inherited from a parent who carries a reciprocal translocation.Case presentationWe present two cases with derivative chromosomes involving a 9.1 Mb 5p deletion/14.8 Mb 10p duplication in the first patient and a 19.9 Mb 5p deletion/ 18.5 Mb 9p duplication in the second patient. These long chromosomal imbalances were ascertained by aCGH but not by conventional cytogenetics. Both patients presented with a deletion of the Cri du chat syndrome region and a duplication of another genomic region. Each patient had a unique clinical picture, and although they presented some features of Cri du chat syndrome, the phenotype did not conclusively point towards this diagnosis, although a chromosomopathy was suspected.ConclusionsThese cases highlight the fundamental role of the clinical suspicion in guiding the approach for the etiological diagnosis of patients. Molecular cytogenetics techniques, such as aCGH, should be considered when the clinician suspects the presence of a chromosomal imbalance in spite of a normal karyotype.

Relato de uma menina com cromossomo derivativo 4 resultante de translocação herdada paterna t(4:18)

“…Cromossomos derivados são descritos como decorrentes de erros meióticos, frequentemente, portadores de translocações equilibradas 8,12 . Assim, o cromossomo derivativo da paciente é resultante de uma translocação cromossômica envolvendo o braço longo do cromossomo 4 na banda q35 com o braço longo do cromossomo 18 na banda q12, levando a trissomia parcial do cromossomo 4q.…”

“…O cromossomo derivativo (der) é representado por um cromossomo rearranjado estruturalmente, abrangendo um ou mais cromossomos ou de mais de um rearranjo no mesmo cromossomo 4 . A literatura mostra que a maioria dos casos de indivíduos com cromossomo derivativo decorre de translocação balanceada nos progenitores, carreando trissomias e monossomias parciais raras [5][6][7][8][9] . Neste contexto, relatamos um caso de uma paciente com o cariótipo 46, XX, der (4)t(4;18), resultante de uma translocação balanceada familiar entre os cromossomos 4 e 18, levando a trissomia parcial do cromossomo 4q.…”

Duplication of 1q31.3q41 in two affected siblings due to paternal insertional translocation

“…Because microarray analysis cannot be used for the detection of balanced chromosome rearrangements (<1% in the aforementioned patient population), methods such as routine cytogenetic analysis or FISH need to be used to detect these rearrangements 18. While microarray should be considered as a first-tier diagnostic test in children with a neurodevelopmental disorder and/or congenital anomalies, it is important to consider using both karyotyping and microarray, especially in families with more than one affected offspring 19.…”

From karyotypes to precision genomics in 9p deletion and duplication syndromes

“…Genomic data were collected from the literature where approximate breakpoints are known for 53 individuals with 9p deletion and duplication syndromes. 12 , 14 , 15 , 16 , 17 , 19 , 27 , 29 , 30 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 …”