Mosaic Tetrasomy of 9p24.3q21.11 postnatally identified in an infant born with multiple congenital malformations: a case report

Abstract

BackgroundSupernumerary Marker Chromosomes consist in structurally abnormal chromosomes, considered as an extra chromosome in which around 70% occur as a de novo event and about 30% of the cases are mosaic. Tetrasomy 9p is a rare chromosomal abnormality described as the presence of a supernumerary isochromosome 9p. Clinical features of tetrasomy 9p include a variety of physical and developmental abnormalities.Case presentationHerein, we reported a postnatal case of a newborn who died in early infancy with multiple congenital malformations due to a mosaic de novo tetrasomy 9p detected by Chromosomal Microarray Analysis. Conventional cytogenetics analysis of the proband was 47,XY,+mar[45]/46,XY[5]. The parental karyotypes presented no visible numerical or structural alterations. Microarray Analysis of the proband revealed that the marker chromosome corresponded to a mosaic de novo gain at 9p24.3q21.11.ConclusionsChromosomal Microarray Analysis was helpful to identify the origin of the supernumerary marker chromosome and it was a powerful tool to carry out genetic diagnostic, guiding the medical diagnosis. Furthermore, the CMA allowed observing at the first time in Central Brazil the tetrasomy 9p and partial tetrasomy 9q in mosaic, encompassing a large duplicated region with several morbid genes, in an infant with multiple congenital malformations.

Integrated CNV-seq, karyotyping and SNP-array analyses for effective prenatal diagnosis of chromosomal mosaicism

“…This study confirms previous modelling of mosaicism where XXX and XO mosaicism was readily detectable at 5% [8]. Although SNP arrays has been demonstrated to be a powerful tool to detect mosaicism at levels as low as 5% by using IlluminaQuad610 array [6], the detectable levels are still variable among different CMA platform (9%-20% for array CGH [18,21] and 30%-70% for Affymetrix arrays [22,23]). Further, when using poor-quality, contaminated or fragmented DNA as the starting template, CNV-seq preforms much better than array CGH platforms for detection of aneuploidy and mosaicism [24].…”

A very rare case of a newborn with tetrasomy 9p and literature review

“…10,11 Tetrasomy 9p was first reported in 1973 by Ghymers and 72 cases have been reported since then. 1,2,[7][8][9][12][13][14][15] Clinical manifestations of the disease include psychomotor retardation (%73), ear deformity (69%), skeletal anomalies (57%), hypertelorism (56%), microretrognathia (46%), urogenital-renal anomalies (43%), eye anomalies (43%), bulbous nose (40%), congenital heart disease (40%), cleft lip and/or palate (33%), clino-camptodactyly (26%), down slanting lips (24%) and microcephaly (20%) (Table I). 1,2,14,[16][17][18][19][20] Although most isochromosomes are maternal in origin, no correlation between maternal age and this chromosomal pathology seems to exist.…”

“…According to the already existing literature, 78% of patients have central nervous system malformations, with ventriculomegaly and Dandy-Walker malformation being the most frequently detected anomalies. 1,2,16,19,[21][22][23][24][25][26][27][28][29][30][31][32][33] The present patient had bilateral ventriculomegaly, vermian hypoplasia, corpus callosum agenesis and brain stem hypoplasia. This condition is very rarely encountered, and affected individuals do not survive, particularly when in non-mosaic condition.…”

“…1 About 30% of the tetrasomy 9p cases are in mosaic state. 2 Although mosaic cases may be phenotypically normal or mildly affected, most cases in non-mosaic constitution are lethal in the early postnatal period due to severe malformations. 3,4 Herein, we report on a newborn with tetrasomy 9p who died at postnatal 22nd day due to severe cardiovascular collapse.…”

Integrated CNV-seq, Karyotyping and SNP-array Analyses for Effective Prenatal Diagnosis of Chromosomal Mosaicism

“…This is equal to the level reported by DNA models mimicking XXX and XO mosaicism [8] and supports the contention that CNV-seq is able to resolve lower levels of mosaicism than CMA. Although SNP arrays has been demonstrated to be a powerful tool to detect mosaicism at levels as low as 5% by using IlluminaQuad610 array [5], the detected rate is still variable among different CMA platform (9%-20% for array CGH [13,16] and 30%-70% for Affymetrix arrays [17,18]). Besides, it perform poorly on array CGH platforms with poor-quality, contaminated or fragmented DNA when compared with CNV-seq [19].…”