Expansion in size of a terminal deletion: a paradigm shift for parental follow-up studies

Abstract

Traditional parental follow-up studies would have not identified this expansion, but would have rather classified the deletion in the daughter as either de novo or benign. Only by sizing the deletion by array comparative genomic hybridisation in both the mother and the daughter was the expansion recognised. Previous assumptions about chromosome behaviour suggest that this phenomenon may have been easily missed in other cases of chromosomal deletions. Therefore, this case illustrates the need for more comprehensive analyses of parental chromosome structure when characterising an abnormality in a child.

Interstitial deletion of 11q in a mother and fetus: implications of directly transmitted chromosomal imbalances for prenatal genetic counseling

“…Undetected mosaicism for a normal cell population in a parent may explain a milder phenotype compared to a nonmosaic child. Chromosome deletions may undergo changes during meiosis, leading to a greater imbalance in the offspring, compared to the transmitting parent, as illustrated by a recent report of expansion in size of a subtelomeric deletion in a normal mother to a cytogenetically visible terminal deletion in her abnormal child (South et al, 2008). Finally, other unidentified genetic, epigenetic and environmental factors may modify the phenotype of a chromosomal abnormality, just as they contribute to phenotypic variation among the normal population.…”

Skin Lesions in a Boy With X-linked Lymphoproliferative Disorder: Comparison of 5 SH2D1A Deletion Cases

“…19 This hypothesis was not confirmed; the deletions in both cousins were identical, involving only SH2D1A and ODZ1. The phenotypic impact of the ODZ1 defect is unclear.…”

A three-step workflow procedure for the interpretation of array-based comparative genome hybridization results in patients with idiopathic mental retardation and congenital anomalies

“…54 For instance, unmasking of a recessive mutation (see criterion 2, Refs. 51, 69), an alteration of the size of the imbalance, 24 position effects, 56 -58 and subclinical, unrecognized manifestations in the carrier parent are still consistent with a pathogenic contribution of a given CNC. An additional complication is the recent description of highly variable phenotypes in subjects with microdeletions in regions such as 1q21.1 and 15q13.3.…”

“…To account for this, and to avoid confusion, the term CNC, rather than CNV has been proposed. 24,25 Detection of significant numbers of CNCs in healthy individuals has presented us with the challenge of distinguishing phenotypically neutral CNCs from those contributing to the patient's phenotype. 21,22 …”