Identification of an unusual marker chromosome by spectral karyotyping

Abstract

We ascertained a newborn girl with multiple congenital anomalies including severe hypotonia, cardiovascular defects, hearing loss, central nervous system anomalies, and facial anomalies. The infant died at 12 days. Cytogenetic analysis showed a de novo supernumerary marker chromosome. Fluorescence in situ hybridization (FISH) with a combination of chromosome specific alpha-satellite probes and an all-human centromere probe failed to show hybridization to the marker, indicating that the marker chromosome lacked detectable alpha satellite sequences. Spectral karyotyping (SKY) was performed and showed that the marker was chromosome 15 in origin. This was confirmed by FISH with a 15q specific subtelomerie probe, which showed hybridization to both ends of the marker chromosome. Based on FISH information and G-banding pattern, the marker was determined to be an inverted duplication of 15q25-qter, leading to partial tetrasomy for chromosome 15. Although the marker chromosome lacked detectable centromeric alpha-satellite sequences, it seemed to have a functional centromere as it is mitotically stable. This observation is consistent with previous studies on acentric marker chromosomes, which suggested that the DNA sequence at the breakpoint could function similarly to alpha-satellite sequences once activated through marker formation.

Clinical, cytogenetic, and molecular analyses of prenatally diagnosed mosaic tetrasomy for distal chromosome 15q and review of the literature

“…Bilateral hydronephrosis was previously observed by Van den Enden et al (1996) at 29 weeks' gestation in a case with tetrasomy for chromosome 15q25-qter. Other associated cardiac defects include a large atrial septal defect and an open ductus arteriosus with a considerable left-right shunt (Van den Enden et al, 1996), dysplastic mitral and aortic valves, and a ventricular septal defect, coarctation of the aorta and aortic arch hypoplasia (Huang et al, 1998). Our case was associated with tetrasomy for chromosome 15q25.3-qter but presented only gastric dilation on prenatal ultrasound.…”

“…Tetrasomy for distal chromosome 15q due to an inverted duplication of distal 15q has been described previously in nine cases (Blennow et al, 1994;Van den Enden et al, 1996;Depinet et al, 1997;Huang et al, 1998;Rowe et al, 2000;Spiegel et al, 2003). Reported breakpoints were at 15q23, 15q24, 15q25, and 15q25.3, resulting in different sized tetrasomies but a consistent *Correspondence to: Chih-Ping Chen, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei, Taiwan, Republic of China.…”

Mosaic tetrasomy 8q: Inverted duplication of 8q23.3qter in an analphoid marker

“…Chromosome painting probes can provide confirmation of the origin of the marker, if the karyotype gives a preliminary indication [Abeliovich et al, 1996; Vance et al, 1997]. Spectral karyotyping [Huang et al, 1998] and subtelomeric probes (present study) can be used for other, unidentifiable acentric markers. The simpler method is to use subtelomeric probes, when the acentric marker involves the telomeric region.…”

The clinical application of spectral karyotyping (SKY™) in the analysis of prenatally diagnosed extra structurally abnormal chromosomes (ESACs)

“…SKY has also been used to determine the origin of postnatally detected chromosome aberrations associated with phenotypic and developmental abnormalities. Huang et al analyzed a newborn with multiple congenital anomalies and a de novo ESAC, subsequently shown by SKY to originate from the distal long arm of chromosome 15 (Huang et al, 1998). Morelli et al reported a child with congenital malformations, previously associated with trisomy 17p.…”