A Rare, Recurrent,De Novo14q32.2q32.31 Microdeletion of 1.1 Mb in a 20-Year-Old Female Patient with a Maternal UPD(14)-Like Phenotype and Intellectual Disability

Abstract

We present a 20-year-old female patient from Indonesia with intellectual disability (ID), proportionate short stature, motor delay, feeding problems, microcephaly, facial dysmorphism, and precocious puberty who was previously screened normal for conventional karyotyping, fragile X testing, and subtelomeric MLPA analysis. Subsequent genome wide array analysis was performed on DNA from blood and revealed a 1.1 Mb deletion in 14q32.2q32.31 (chr14:100,388,343-101,506,214; hg19). Subsequent carrier testing in the parents by array showed that the deletion had occurred de novo in the patient and that her paternal 14q32 allele was deleted. The deleted region encompasses the DLK1/GTL2 imprinted gene cluster which is consistent with the maternal UPD(14)-like phenotype of the patient. This rare, recurrent microdeletion was recently shown not to be mediated by low copy repeats, but by expanded TGG repeats, flanking the 14q32.2q32.21 deletion boundaries, a novel mechanism of recurrent genomic rearrangement. This is another example how the application of high resolution genome wide testing provides an accurate genetic diagnosis, thereby improving the care for patients and optimizing the counselling for family.

New insights into the imprinted MEG8-DMR in 14q32 and clinical and molecular description of novel patients with Temple syndrome

“…Highly similar deletions have been described in nine cases so far, adding further support to the existence of a recurrent microdeletion syndrome on chromosome 14q32. 2,[14][15][16][23][24][25] TS patient 2 shows severe intellectual disability usually not observed in TS14 patients with upd (14)mat or ID but present in all 1.1 Mb deletion cases. 2 As hypothesized before this might be due to the deletion of the YY1 gene, which has been linked to intellectual disability.…”

Trisomy rescue mechanism: the case of concomitant mosaic trisomy 14 and maternal uniparental disomy 14 in a 15‐year‐old girl

“…Several cases [6][7][8][9] of upd (14)mat-like phenotypes have been published in patients with normal karyotype, supporting the assumption that point mutations or rearrangements at the 14q32 imprinted locus were responsible for clinical features of upd (14)mat. Indeed, in 2007, Tem-ple et al [8] reported the case of an upd (14)mat-like patient with isolated mutation in the DLK1/GTL2 locus.…”

New patients with Temple syndrome caused by 14q32 deletion: Genotype‐phenotype correlations and risk of thyroid cancer

“…Until now, nine cases of TS caused by a paternal deletion have been reported [Kagami et al, ; Mitter et al, ; Béna et al, ; Zada et al, ; Dworschak et al, ; Rosenfeld et al, ]. Here we discuss four new patients with TS due to de novo deletions at 14q32, detected by array‐Comparative Genomic Hybridization (aCGH) and involving the paternal allele, and highlight genotype‐phenotype correlations by comparison with previously reported deletions.…”