Clinical and molecular cytogenetic analyses of four families with 1q21.1 microdeletion or microduplication

Abstract

Background: Little information is available regarding the penetrance of 1q21.1 copy number variants (CNVs). In the present study, we explored the clinical significance of 1q21.1 microdeletion or microduplication.

Methods: In four families, chromosome karyotype was analyzed using G-banding karyotype analysis technology. CNVs were detected using array-comparative genomic hybridization (aCGH) and then a quantitative polymerase chain reaction (qPCR) was used to validate candidate CNVs. Sequence signature in the breakpoint region was analyzed using University of California Santa Cruz (UCSC) databases.

Results: Except for karyotype 45, XX, der (13, 14) (q10, q10) in the mother (I2) of family 2, the karyotype was normal in all other members of the four families. In the mother (I2) and fetus (II2) of family 1, in newborn (II1) of family 2 and in fetus (II1) of family 3, there was 1.22-Mb heterozygous microdeletion in the chromosome 1q21.1q21.2 region. The child (II1) of family 4 had a 1.46-Mb heterozygous microduplication in the chromosome 1q21.1q21.2 region. The results of the qPCR were consistent with that of aCGH. There was large number of low copy repeats (LCRs) in the breakpoint region found by analysis of the UCSC database, and multiple LCRs were matched with sequences in the chromosome 1 short-arm region.

Conclusions: 1q21.1 microdeletion and microduplication exhibit a variety of clinical manifestations and the specificity of their clinical features is not high. The penetrance of the distal 1q21.1 microdeletion may be affected by other factors in the present study. In summary, we report the discovery of a new distal 1q21.1 microduplication, which enriches the CNV spectrum in the 1q21.1 region and is conducive to prenatal genetic counseling.

Keywords: 1q21.1 microdeletion; 1q21.1 microduplication; array-comparative genomic hybridization; copy number variations.

Figure 1

Genealogical tree for the four families in this study. I, parent; II, offspring; □, male; ○, female; ⋄, fetus; black, CNV patient with clinical symptoms; oblique line, CNV patient without clinical symptoms

Figure 2

Fetal encephalomeningocele. Behind the fetal head, there is a 56 × 52 mm fluid sonolucent area that is multilocular as a result of the existence of septations with a 15 × 9 mm high‐level echo

Figure 3

The fetus has complete atrioventricular septal defect. The four‐chamber view of the fetus shows the disappearance of cross section with a 6.75‐mm defect

Figure 4

Tetralogy of Fallot combined with acleistocardia. Left ventricular long‐axis view shows the ventricular septal defect and aortic over‐riding (left). Large arterial short‐axis view shows the main pulmonary artery, left pulmonary artery, right pulmonary artery stenosis and the increased thickness of the right ventricular anterior wall (right)

Figure 5

Results of array comparative genomic hybridization in family 1. As indicated by the arrows, there was the same 1.22‐Mb heterozygous microdeletion with the molecular karyotype of arr[hg19] 1q21.1q21.2(146,564,743–147,786,706) × 1, respectively, in the mother (I2) and fetus (II2)

Figure 6

Results of array comparative genomic hybridization in family 2. As indicated by the arrow, there was a de novo 1.22‐Mb heterozygous microdeletion with the molecular karyotype of arr[hg19] 1q21.1q21.2(146,564,743–147,786,706) × 1 in the newborn (II1)

Figure 7

Results of array comparative genomic hybridization in family 3. As indicated by the arrow, there was a de novo 1.22‐Mb heterozygous microdeletion with the molecular karyotype of arr[hg19] 1q21.1q21.2(146,564,743–147,786,706) × 1 in the fetus (II1)

Figure 8

Results of array comparative genomic hybridization in family 4. As indicated by the arrow, there was a de novo 1.46‐Mb heterozygous microduplication with the molecular karyotype of arr[hg19] 1q21.1q21.2: (146,324,068–147,786,706) × 3 in the child (II1)

Figure 9

The UCSC database indicates a large number of repeated similar fragments in the 1q21.1q21.2 region with CNVs