Heide Solveig, Keren Boris, Billette de Villemeur Thierry, Chantot-Bastaraud Sandra, Depienne Christel, Nava Caroline, Mignot Cyril, Jacquette Aurélia, Fonteneau Eric, Lejeune Elodie, Mach Corinne, Marey Isabelle, Whalen Sandra, Lacombe Didier, Naudion Sophie, Rooryck Caroline, Toutain Annick, Caignec Cédric Le, Haye Damien, Olivier-Faivre Laurence, Masurel-Paulet Alice, Thauvin-Robinet Christel, Lesne Fabien, Faudet Anne, Ville Dorothée, des Portes Vincent, Sanlaville Damien, Siffroi Jean-Pierre, Moutard Marie-Laure, Héron Delphine
APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France; GRC Intellectual Disability and Autism, UPMC, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France.
APHP, GH Pitié-Salpêtrière, Department of genetics, unit of developmental genomic, Paris, France.
J Pediatr. 2017 Jun;185:160-166.e1. doi: 10.1016/j.jpeds.2017.02.023. Epub 2017 Mar 8.
To evaluate the role that chromosomal micro-rearrangements play in patients with both corpus callosum abnormality and intellectual disability, we analyzed copy number variations (CNVs) in patients with corpus callosum abnormality/intellectual disability STUDY DESIGN: We screened 149 patients with corpus callosum abnormality/intellectual disability using Illumina SNP arrays.
In 20 patients (13%), we have identified at least 1 CNV that likely contributes to corpus callosum abnormality/intellectual disability phenotype. We confirmed that the most common rearrangement in corpus callosum abnormality/intellectual disability is inverted duplication with terminal deletion of the 8p chromosome (3.2%). In addition to the identification of known recurrent CNVs, such as deletions 6qter, 18q21 (including TCF4), 1q43q44, 17p13.3, 14q12, 3q13, 3p26, and 3q26 (including SOX2), our analysis allowed us to refine the 2 known critical regions associated with 8q21.1 deletion and 19p13.1 duplication relevant for corpus callosum abnormality; report a novel 10p12 deletion including ZEB1 recently implicated in corpus callosum abnormality with corneal dystrophy; and) report a novel pathogenic 7q36 duplication encompassing SHH. In addition, 66 variants of unknown significance were identified in 57 patients encompassed candidate genes.
Our results confirm the relevance of using microarray analysis as first line test in patients with corpus callosum abnormality/intellectual disability.
为评估染色体微重排在胼胝体异常和智力残疾患者中所起的作用，我们分析了胼胝体异常/智力残疾患者的拷贝数变异（CNV）。研究设计：我们使用Illumina SNP阵列对149例胼胝体异常/智力残疾患者进行了筛查。
在20例患者（13%）中，我们鉴定出至少1种可能导致胼胝体异常/智力残疾表型的CNV。我们证实，胼胝体异常/智力残疾中最常见的重排是8号染色体末端缺失的反向重复（3.2%）。除了鉴定已知的复发性CNV，如6qter、18q21（包括TCF4）、1q43q44、17p13.3、14q12、3q13、3p26和3q26（包括SOX2）缺失外，我们的分析还使我们能够细化与胼胝体异常相关的8q21.1缺失和19p13.1重复的两个已知关键区域；报告一个新的10p12缺失，包括最近与伴有角膜营养不良的胼胝体异常有关的ZEB1；并报告一个新的包含SHH的致病性7q36重复。此外，在57例包含候选基因的患者中鉴定出66种意义不明的变异。
我们的结果证实了在胼胝体异常/智力残疾患者中使用微阵列分析作为一线检测方法的相关性。
