Centro Universitário Autônomo do Brasil, Curitiba, PR, Brazil.
Faculdade Evangélica Mackenzie do Paraná, Curitiba, PR, Brazil.
Rev Paul Pediatr. 2023 Jan 20;41:e2021387. doi: 10.1590/1984-0462/2023/41/2021387. eCollection 2023.
Autism spectrum disorder (ASD) affects cognitive development and social interaction on different levels. Genetic and environmental factors are associated with secondary ASD. Genetic inheritance is mainly polygenic, and 10% are copy number variations (CNVs). Array comparative genomic hybridization (array-CGH) is used to identify CNVs. This report aimed to discuss autism spectrum disorder and its diagnosis by array comparative genomic hybridization, highlighting the association with the pathogenic duplication of 17q12q21.2.
A male baby was born at 37 weeks' gestation by cesarean section. The child showed strabismus, cryptorchidism, hypertelorism, frontal bossing, and developmental delay, walking at 25 months and talking at 4 years. At the age of 2 years, array-CGH of peripheral blood revealed a 5.6-Mb 17q12q21.2 duplication or arr 17q12q21.2 (34,815,527-40,213.109)x3 encompassing 190 genes, including HNF-1B and LHX1. The child was clinically diagnosed with ASD.
Changes in the 17q12 segment, such as the duplication found, have been associated with the development of several problems in previous studies, mainly kidney diseases and behavioral disorders. Located at this chromosome region, HNF1's homeobox B codes a member of the superfamily containing homeodomain of transcription factors. Another gene associated with abnormalities in neurological development regarding 17q12 deletions is LHX1, as shown in this case study. LHX1 plays a role in the migration and differentiation of GABA neurons, modulating the survival of pre-optical interneurons, thus affecting cellular migration and distribution in the cortex. Changes in this control result in flaws in interneuron development, contributing to the pathophysiology of psychiatric diseases.
自闭症谱系障碍（ASD）在不同层面上影响认知发展和社交互动。遗传和环境因素与继发性 ASD 有关。遗传继承主要是多基因的，10%是拷贝数变异（CNV）。阵列比较基因组杂交（array-CGH）用于识别 CNV。本报告旨在通过阵列比较基因组杂交讨论自闭症谱系障碍及其诊断，重点讨论与致病性 17q12q21.2 重复相关的问题。
一名男婴经剖宫产于 37 周时出生。该患儿表现为斜视、隐睾、眼距过宽、额骨突出和发育迟缓，25 个月时会走路，4 岁时会说话。2 岁时，外周血 array-CGH 显示 17q12q21.2 处 5.6Mb 重复或 arr 17q12q21.2（34,815,527-40,213.109）x3，包含 190 个基因，包括 HNF-1B 和 LHX1。该患儿被临床诊断为 ASD。
在先前的研究中，17q12 片段的变化，如发现的重复，与多种问题的发展有关，主要是肾脏疾病和行为障碍。位于该染色体区域的 HNF1 同源盒 B 编码转录因子同源结构域超家族的成员。另一个与 17q12 缺失有关的神经发育异常的基因是 LHX1，如本病例研究所示。LHX1 在 GABA 神经元的迁移和分化中起作用，调节视前中间神经元的存活，从而影响皮质中的细胞迁移和分布。这种控制的变化导致中间神经元发育缺陷，有助于精神疾病的病理生理学。
