%0 Journal Article
%T A Rare, Recurrent, De Novo 14q32.2q32.31 Microdeletion of 1.1£żMb in a 20-Year-Old Female Patient with a Maternal UPD(14)-Like Phenotype and Intellectual Disability
%A Almira Zada
%A Farmaditya E. P. Mundhofir
%A Rolph Pfundt
%A Nico Leijsten
%A Willy Nillesen
%A Sultana M. H. Faradz
%A Nicole de Leeuw
%J Case Reports in Genetics
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/530134
%X 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£żMb 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. 1. Introduction The application of high resolution genome wide array analysis provides an accurate genetic diagnosis in many patients with ID and/or congenital anomalies caused by genomic imbalances. The use of this technology has led to the discovery of several novel microdeletion and microduplication syndromes. Although several patients have been reported with a terminal 14q32 deletion, patients with an in terstitial microdeletion in the 14q32 region seem to be rare. To our knowledge, only two patients with an interstitial 1.1£żMb deletion in q32.2q32.31 have previously been reported [1, 2]. Human chromosome 14q32.2 is the critical region for uniparental disomy of chromosome 14 (UPD(14)) phenotypes because it carries a cluster of imprinted genes, including the paternally expressed genes (PEGs) such as DLK1&RTL1 and the maternally expressed genes (MEGs) such as GTL2 (also known as MEG3), RTL1as (RTL1 antisense), and MEG8. Deletion of the paternal allele in this region causes a UPD(14)mat-like phenotype [3]. Uniparental disomy (UPD) occurs when the two copies of a chromosome pair are inherited from only one parent [4]. Maternal UPD of chromosome 14 (UPD(14)mat) is characterized by pre- and postnatal growth retardation, hypotonia, feeding problems, motor delay, short stature, early onset of puberty, and minor dysmorphic features of the face, hands, and feet [5].
%U http://www.hindawi.com/journals/crig/2014/530134/