Publications by authors named "Una Maye"

5 Publications

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Clinical and molecular characterization of the 20q11.2 microdeletion syndrome: six new patients.

Am J Med Genet A 2015 Mar 8;167A(3):504-11. Epub 2015 Jan 8.

Unité de Génétique Médicale et Oncogénétique, Centre Hospitalier Universitaire Amiens Picardie, Amiens, France; Laboratoire de Cytogénétique et Biologie de la Reproduction, Centre Hospitalier Universitaire Amiens Picardie, Amiens, France.

Interstitial microdeletions of 20q chromosome are rare, only 17 patients have been reported in the literature to date. Among them, only six carried a proximal 20q11.21-q11.23 deletion, with a size ranging from 2.6 to 6.8 Mb. The existence of a 20q11.2 microdeletion syndrome has been proposed, based on five previously reported cases that displayed anomalies of the extremities, intellectual disability, feeding difficulties, craniofacial dysmorphism and variable malformations. To further characterize this syndrome, we report on six new patients with 20q11.2 microdeletions diagnosed by whole-genome array-based comparative genomic hybridization. These patient reports more precisely refined the phenotype and narrowed the minimal critical region involved in this syndrome. Careful clinical assessment confirms the distinctive clinical phenotype. The craniofacial dysmorphism consists of high forehead, frontal bossing, enophthalmos, and midface hypoplasia. We have identified a 1.62 megabase minimal critical region involved in this syndrome encompassing three genes—GDF5, EPB41L1, andSAMHD1—which are strong candidates for different aspects of the phenotype. These results support that 20q11.2 microdeletion syndrome is a new contiguous gene deletion syndrome with a recognizable phenotype.
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http://dx.doi.org/10.1002/ajmg.a.36882DOI Listing
March 2015

Exonic deletions in AUTS2 cause a syndromic form of intellectual disability and suggest a critical role for the C terminus.

Am J Hum Genet 2013 Feb 17;92(2):210-20. Epub 2013 Jan 17.

Department of Clinical Genetics, VU University Medical Center, Amsterdam 1007 MB, The Netherlands.

Genomic rearrangements involving AUTS2 (7q11.22) are associated with autism and intellectual disability (ID), although evidence for causality is limited. By combining the results of diagnostic testing of 49,684 individuals, we identified 24 microdeletions that affect at least one exon of AUTS2, as well as one translocation and one inversion each with a breakpoint within the AUTS2 locus. Comparison of 17 well-characterized individuals enabled identification of a variable syndromic phenotype including ID, autism, short stature, microcephaly, cerebral palsy, and facial dysmorphisms. The dysmorphic features were more pronounced in persons with 3'AUTS2 deletions. This part of the gene is shown to encode a C-terminal isoform (with an alternative transcription start site) expressed in the human brain. Consistent with our genetic data, suppression of auts2 in zebrafish embryos caused microcephaly that could be rescued by either the full-length or the C-terminal isoform of AUTS2. Our observations demonstrate a causal role of AUTS2 in neurocognitive disorders, establish a hitherto unappreciated syndromic phenotype at this locus, and show how transcriptional complexity can underpin human pathology. The zebrafish model provides a valuable tool for investigating the etiology of AUTS2 syndrome and facilitating gene-function analysis in the future.
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http://dx.doi.org/10.1016/j.ajhg.2012.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567268PMC
February 2013

Interstitial microduplication of Xp22.31: Causative of intellectual disability or benign copy number variant?

Eur J Med Genet 2010 Mar-Apr;53(2):93-9. Epub 2010 Feb 2.

McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.

The use of comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays has dramatically altered the approach to identification of genetic alterations that can explain intellectual disability and /or congenital anomalies. However, the discovery of numerous copy number changes with benign or unknown clinical significance has made interpretation problematic. Submicroscopic duplication of Xp22.31 has been reported as either a possible cause of intellectual disability and/or developmental delay or a benign variant. Here we report 29 individuals with the microduplication found as part of microarray analysis of 7793 samples submitted to an international group of 13 clinical laboratories. The referral reasons varied and included developmental delay, intellectual disability, autism, dysmorphic features and/or multiple congenital anomalies. The size of the Xp22.31 duplication varied between 149 kb and 1.74 Mb and included the steroid sulfatase (STS) gene with the male to female ratio of 0.7. Duplication within this segment is seen at a frequency of 0.15% in a healthy control population, whereas a frequency of 0.37% was observed in our cohort of individuals with abnormal phenotypes. We present a detailed comparison of the breakpoints, inheritance, X-inactivation and clinical phenotype in our cohort and a review of the literature for a total of 41 patients. To date, this report is the largest compilation of clinical and array data regarding the microduplication of Xp22.31 and will serve to broaden the knowledge of regions involving copy number variation (CNV).
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http://dx.doi.org/10.1016/j.ejmg.2010.01.004DOI Listing
July 2010

Interstitial deletion of the short arm of chromosome 2 in a mother and child, with facial dysmorphism and mild learning difficulties.

Clin Dysmorphol 2006 Oct;15(4):221-3

Cheshire and Merseyside Medical Genetics Service, Department of Clinical Genetics, Royal Liverpool Children's Hospital, Alder Hey, Liverpool, UK.

We report a mother and son with an interstitial deletion of chromosome 2: del(2)(p21p22.2). Both have mildly dysmorphic facial features and learning difficulties. This phenotype contrasts with two previously described cases with a similar deletion that presented with cyclopia and alobar holoprosencephaly.
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http://dx.doi.org/10.1097/01.mcd.0000220620.85896.0fDOI Listing
October 2006

Isochromosome 20p associated with multiple congenital abnormalities.

Clin Dysmorphol 2005 Jan;14(1):49-50

Department of Clinical Genetics, Royal Liverpool Children's Hospital dDepartment of Obstetrics,Liverpool, England.

A second case of tetrasomy 20p due to an additional isochromosome 20p is reported. This resulted in a spontaneous intrauterine death with multiple congenital abnormalities. In keeping with the previous report, the foetus had poor ossification resulting in multiple long bone fractures.
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http://dx.doi.org/10.1097/00019605-200501000-00012DOI Listing
January 2005