Rare deletion of 362 Kb on chromosome 16p11.2 in two brothers with developmental delay and autism

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Rare deletion of 362 Kb on chromosome 
16p11.2 in two brothers with developmental 
delay and autism 
 
Chaves, T.F.¹, Oliveira, L.F.¹, Ocampos, M.², Barbato, I.T.², De Luca, G.R.³, Pinto, L.L.C.³, Filho, J.H.B.²; 
Maris, A.F.¹. 
¹Universidade Federal de Santa Catarina – Florianópolis – SC; ²Laboratório Neurogene –Florianópolis – SC; ³Hospital 
Infantil Joana de Gusmão – Florianópolis – SC, Brazil. 
 
labneurogeneticaufsc@gmail.com 
 
Keywords: Developmental Brain Disorders; array-CGH; Autism; 16p11.2; Microdeletions. 
 
 
Autism is a Developmental Brain Disorder (DBD) presenting clinical characteristics related to deficits of reciprocal social 
interaction, impairment of verbal communications, restricted interests and repetitive behaviors. Due to the hereditary character 
of approximately 90%, autism stands out as one of the most hereditary complex diseases, where in approximately 10% of the 
cases the disorder can be explained by genetic syndromes and known chromosomal anomalies. With the recent consolidation of 
microarray as a first-line genetic test in DBD research, it has been possible to detect genomics imbalances with high resolution 
revealing candidate regions/genes for autism. One of the best known regions is an allelic loss (a Copy Number Variation - CNV) 
on chromosome 16p11.2, usually of 500 to 600 kbp, involving about 29 genes, precisely on breakpoints 4-5 (BP4-BP5) (~29.6-
30.2 Mbp from the telomere according to the human genome GRCh37/hg19). Here we report two cases of nonsyndromic 
autistic siblings (5 and 6 years old) who present a 362 kbp microdeletion outside, but directly adjacent to the classical region of 
the 16p11.2 deletion syndrome. The aCGH exam (Affymetrix CytoScan® HD) were requested by a doctor geneticist in 2013 and 
carried out by the Neurogene Laboratory (Florianópolis - Brazil), through the sample of patients' blood constitutional cells. The 
analysis was done using the Chromosome Analysis Suite (Affymetrix®, USA) software. Clinical significance was established by 
comparing each unbalanced genomic region to information from public & private databases. In both array-CGH results, 3 CNVs 
were detected: i) a microdeletion of 151 kbp on chromosome 9 ([hg19] 9q21.2 (79,995,132-80,146,062) x1) covering 2 OMINs 
genes (VPS13A (vacuolar protein sorting 13) and GNA14 (G protein subunit alpha 14; ii) a 362 kpb microdeletion on 
chromosome 16 ([hg19] 16p11.2 (28,689,085-29,043,863)x1), involving 11 OMIM genes (CEIF3C, ATXN2L, TUFM, SH2B1, 
ATP2A1, RABEP2, CD19, NFATC2IP, SPNS1 and LAT), the most relevant being the ATP2A1 gene (OMIM*108730), 
encoding a calcium transport ATPase whose function is to decrease the cytoplasmic concentration of Ca (2+), the SH2B1 gene 
(OMIM#608937) (ADAPTOR PROTEIN 1) that plays a role in insulin and leptin signaling, associated with developmental 
delay and obesity; iii) a 289 kbp microduplication in 16 ([hg19] 16p11.2 (34,466,678-34,755,816)x3) without OMINs genes. We 
conclude that among the genomics findings, the 9q21.2 microdeletion and 16p11.2 microduplication are benign variants 
regarding this DBD. Based on the data genomics databases and scientific publications, we attribute the cause of the patients 
phenotype (non-syndromic autism) to the 362 kbp microdeletion in 16p11.2. The Deletions of the 16p11.2 SH2B1-containing 
region are pathogenic and usually associated with developmental delay in addition to obesity. 
 
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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