We report on a female patient who presented with severe intellectual disability and autistic behavior, dysmorphic features, orodental anomalies, and bilateral calcification of basal ganglia. Using a high-density oligonucleotide microarray, we have identified a de novo duplication of 11q13.1q22.1 involving the dosage sensitive genes FGF3 and FGF4, genes related to autosomal dominant disorders KMT5B, GAL, SPTBN2, and LRP5, susceptibility loci SCZD2, SLEH1, and SHANK2, mitochondrial genes NDUFV1, NDUFS8, and TMEM126B, and many loss of function genes, including PHOX2A, CLPB, MED17, B3GNT1, LIPT2, and CLPB. However, the duplication did not involve Ribonuclease H2, subunit C (RNASEH2C) which is considered to be located in the critical region for Aicardi-Goutières syndrome. In combination with the duplication at 11q13.1, a 1.849-Mb heterozygous duplication at 4q35.2 was also identified. Although this duplicated region does not contain causative genes related to brain calcification, the duplication at 4q35 was reported previously in a patient with basal ganglia calcification, coats' like retinopathy, and glomerulosclerosis. Our patient's presentation and genomic findings indicate that duplication of 4q35.2 could be a novel genetic cause of calcification of basal ganglia. Our report also underscores the clinical significance of rearrangements in 11q13.1q22.1 in the pathogenesis of basal ganglia calcification.

中文翻译：

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具有新表型特征的 11q13.1q22.1 和 4q35.2 重复患者的双侧基底节钙化

我们报告了一名女性患者，她表现出严重的智力障碍和自闭症行为、畸形特征、口腔异常和双侧基底节钙化。我们使用高密度寡核苷酸微阵列鉴定了 11q13.1q22.1 的从头复制，涉及剂量敏感基因 FGF3 和 FGF4、与常染色体显性遗传病 KMT5B、GAL、SPTBN2 和 LRP5 相关的基因，易感基因座 SCZD2、SLEH1和 SHANK2、线粒体基因 NDUFV1、NDUFS8 和 TMEM126B，以及许多功能缺失基因，包括 PHOX2A、CLPB、MED17、B3GNT1、LIPT2 和 CLPB。然而，复制不涉及核糖核酸酶 H2，亚基 C (RNASEH2C)，它被认为位于 Aicardi-Goutières 综合征的关键区域。结合 11q13.1 处的重复，一个 1。还鉴定了 4q35.2 处的 849-Mb 杂合重复。尽管该重复区域不包含与脑钙化相关的致病基因，但先前在患有基底神经节钙化、大衣样视网膜病变和肾小球硬化的患者中报告了 4q35 的重复。我们患者的表现和基因组发现表明 4q35.2 的重复可能是基底神经节钙化的新遗传原因。我们的报告还强调了 11q13.1q22.1 重排在基底神经节钙化发病机制中的临床意义。和肾小球硬化。我们患者的表现和基因组发现表明 4q35.2 的重复可能是基底神经节钙化的新遗传原因。我们的报告还强调了 11q13.1q22.1 重排在基底神经节钙化发病机制中的临床意义。和肾小球硬化。我们患者的表现和基因组发现表明 4q35.2 的重复可能是基底神经节钙化的新遗传原因。我们的报告还强调了 11q13.1q22.1 重排在基底神经节钙化发病机制中的临床意义。