First case description of Temple Syndrome due to 14q32.2-q32.3 microdeletion in Brazil

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First case description of Temple Syndrome 
due to 14q32.2-q32.3 microdeletion in 
Brazil 
Oliveira, L.F.¹; Chaves, T.F.¹; Ocampos, M.²; Barbato, I.T.²; Bernardi, P.³; Maris, A.F.¹. 
¹Universidade Federal de Santa Catarina – Florianópolis/SC; ²Laboratório Neurogene – Florianópolis/SC; ³Hospital 
Universitário Professor Polydoro Ernani de São Thiago – Florianópolis/SC. 
 
labneurogeneticaufsc@gmail.com 
 
Keywords: Temple Syndrome, Chromosome 14q32, Array Comparative Genomic Hybridization (aCGH). 
 
 
The Temple Syndrome (TS) was first described by Temple in 1991, caused by altered imprinted gene expression at chromosome 
14q32. The imprinting locus on chromosome 14 has a cluster of imprinted genes, where the maternally imprinted protein coding 
genes DLK1, RTL1 and DIO3 are expressed only from the paternal allele, while the paternally imprinted genes, expressed only 
from the maternal allele, are all non-coding RNAs (GTL2 / MEG3, MEG8, RTL1, in addition to several miRNAs and 
snoRNAs). To date three causes have been described that lead to TS. Over 75% of the reported cases are due to maternal 
uniparental disomy of chromosome 14 (UPD14mat). More recently cases of paternal deletion or altered methylation at the 
intergenic differentially methylated region (IG-DMR) were described, leading to the conclusion that the absence of the 
expression of DLK1, RTL1 and DIO3 is the main cause of the syndrome. The clinical features of TS are: Pre- and postnatal 
growth retardation, hypotonia, motor delay, joint laxity, feeding problems early in life, early puberty, obesity, short stature, facial 
features include a broad forehead and short nose with a wide nasal tip, and the majority of patients have small hands and feet. 
Until now only thirteen cases have been described from a paternal deletion. Here we present an additional patient with a deletion 
in this region being the first case described in Brazil, with the purpose of to bring this syndrome to the attention of health 
professionals. The patient is a 9 years old female, which has neuropsychomotor developmental delay, intellectual disability, cleft 
palate, dysmorphic facies, short stature, eye anomalies and early puberty. This study was performed by request of the aCGH 
exam (Affymetrix CytoScan® HD) by a doctor geneticist in 2015 and performed by the Neurogene Laboratory (Florianópolis - 
Brazil). The analysis was done using Chromosome Analysis Suite® (Affymetrix Inc., EUA) and identified a microdeletion of 
2.660 Kbp on chromosome 14, region 14q32.2-q32.3, linear position (chr14:100,095,248-102,755,064; hg19). In this region 17 
genes related to Mendelian disorders were identified: CYP46A1, EML1, DEGS2, YY1, SLC25A29, SLC25A47, WARS, DLK1, 
MEG3 or GTL2, RTL1, DIO3OS, DIO3, PPP2R5C, DYNC1H1, HSP90AA1, MDK e MEG8, 20 miRNAs and 3 snoRNAs. In 
conclusion, we present in this study a rare microdeletion in 14q32.2 identified using high resolution genome wide array analysis. 
The deleted region includes the set of imprinting genes DLK1/GTL2 which is consistent with a part of the patient's phenotype. 
The haploinssuficiency of the YY1 gene may be responsible for the intellectual disability. This study evidences the importance of 
the application of high resolution genome tests to carry out an accurate genetic diagnosis, thereby improving care for patients 
and counseling for the family. 
 
 
Financial Support: CAPES, PPSUS. 
 
 
 
 
 
 
 
 
 
 
Resumos do GENÉTICA 2017 - Brazilian-International Congress of Genetics • 12 a 15 de setembro de 2017 
Hotel Monte Real Resort • Águas de Lindóia • SP • Brasil 
www.sbg.org.br - ISBN 978-85-89109-06-2 
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