Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil

Abstract

ABSTRACT. In several patients, intellectual disability and/or congenital malformation may be attributed to chromosomal changes. In this study, we conducted an array-CGH test of 200 patients from the Northeast of Brazil with intellectual disability and/or congenital malformation. Blood samples were collected from the proband and from their parents when possible. DNA was extracted and investigated using the array-CGH test. Findings were evaluated for the pathogenicity in databases of benign and pathogenic changes (ISCA, UCSC, DGV, and DECIPHER). Forty-seven copy number variations (CNVs) were identified in 43/200 (21.5%) patients, including 25/98 (25.5%) in males and 22/102 (21.57%) in females. We considered 33 of these to be clinically significant, reaching a diagnosis rate of 16.5%. The sizes of the CNVs varied from 102 kb to 24 Mb in deletions and from 115 kb to 140 Mb in duplications. In 10/47 (21.3%) patients, the rearrangement involved a sex chromosome. Thirty-nine patients had one chromosomal aberration, while 2 concomitant abnormalities were detected in 4 patients. Ten of 47 CNVs (21.3%) were > 5Mb in size. Fifteen patients had CNVs related to known syndromes. This research highlights the contribution of submicroscopic chromosomal changes to the etiology of intellectual disability and/or congenital malformation, particularly the implication of chromosomal abnormalities detected using an array-CGH test, with a high rate of 16.5%. Thus, our results support the use of array-CGH replacing standard karyotype as the first-tier cytogenetic diagnostic test for patients with multiple congenital anomalies and/or intellectual disability.

Phenotype comparison among individuals with developmental delay/intellectual disability with or without genomic imbalances

“…In this study, the CMA in 63 individuals with DD/ID revealed pathogenic CNVs in 20 (32%) cases. This diagnostic yield is higher than the yields obtained in earlier studies (Miller et al 2010;Wincent et al 2011;Palmer et al 2014;Vianna et al 2016;Di Gregorio et al 2017). However, the reason for this higher detection rate was the inclusion of 12 individuals with abnormal karyotype results prior to the CMA.…”

“…In South America, very few studies performing CMA in individuals with DD/ID exist (Krepischi-Santos et al 2006;Lay-Son et al 2015;Vianna et al 2016;Zanardo et al 2017). However, none of them compared the clinical features among individuals with or without GIs.…”

Microarreglos cromosómicos en 236 pacientes chilenos con trastornos del neurodesarrollo y anomalías congénitas

“…Se destaca en este trabajo el tamaño de la muestra, que sería la más grande reportada en Sudamérica 12,17,18 y que se incluyeron pacientes provenientes de todo Chile, lo que contribuye, con mayor precisión, a conocer la prevalencia de este tipo de alteraciones genéticas en la población chilena. Por otro lado, es importante destacar que la asociación de un diagnóstico positivo por CMA con factores como el sexo del paciente, edad y el tipo de diagnóstico no habían sido descritos antes en población chilena.…”

“…Tanto los TN como las AC se manifiestan en la infancia, lo que amerita su derivación en esta etapa de la vida 1,2 . La tasa de diagnóstico de 19% estimada en el presente estudio podría ser considerada como la prevalencia de estos desbalances en población chilena con TN, AC o ambos, lo que concuerda además con las cifras promedio reportadas internacionalmente (entre 15 a 20%) 11,17,18 . Sin embargo, esta podría ser mayor, ya que en el estudio previo realizado en Chile 12 se detectó variantes clínicamente significativas en 25% de los pacientes, porcentaje que sube a cerca de 29%, si se consideran solo aquellos pacientes con cariotipo convencional normal.…”

Нови Геномни Технологии При Диагностиката На Вродени Аномалии

“…Благодарение на високата си резолюция и чувствителност, микрочиповата технология се превърна в ключов подход при диагностицирането на пациенти с множество вродени малформации, и/ или умствено увреждане [21].…”