Hyperkinetic stereotyped movements in a boy with biallelic CNTNAP2 variants.
Hyperkinetic stereotyped movements in a boy with biallelic CNTNAP2 variants.
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DOI：
10.1186/s13052-021-01162-w
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发表时间：
2021-10-12
影响因子：
3.6
通讯作者：
Striano P
中科院分区：
文献类型：
--
作者：
Scala M;Anijs M;Battini R;Madia F;Capra V;Scudieri P;Verrotti A;Zara F;Minetti C;Vernes SC;Striano P
CNTNAP 2中的杂合变体与广泛的神经学表型有关，包括智力残疾（ID）、癫痫、自闭症谱系障碍（ASD）和语言障碍。然而，杂合子变体也可以在未受影响的个体中发现。双等位基因CNTNAP 2变体更罕见，并导致一种明确定义的遗传综合征，称为CASPR 2缺乏症，这种疾病的特征是ID，早发性难治性癫痫，语言障碍和自闭症特征。一个7岁的男孩提出了多动定型运动，开始于婴儿早期，并持续到童年。异常运动表现为四肢有节奏、重复性的抖动，具有明显的刻板特征。其他临床特征包括ID、注意力缺陷多动障碍（ADHD）、ASD和语言障碍，与CASPR 2缺乏症一致。全基因组阵列比较基因组杂交检测到一个母系遗传的0.402 Mb重复，涉及CNTNAP 2的内含子1、外显子2和内含子2（c.97 +？209-？up）。内含子1中的受影响区域含有转录因子FOXP 2的结合位点，可能导致CNTNAP 2表达调控异常。CNTNAP 2编码区的桑格测序也鉴定了父系遗传的错义变体c.2752C > T，p.（Leu918Phe）。该病例扩大了CASPR 2缺乏症的分子和表型谱，表明多动刻板运动可能是这种复杂神经系统疾病的罕见但重要的临床特征。此外，在CNTNAP 2中识别出框内的、主要是非编码重复，指出了一种复杂的潜在分子机制，可能涉及受损的FOXP 2结合。在线版本包含补充材料，可通过10.1186/s13052-021-01162-w获得。
Heterozygous variants in CNTNAP2 have been implicated in a wide range of neurological phenotypes, including intellectual disability (ID), epilepsy, autistic spectrum disorder (ASD), and impaired language. However, heterozygous variants can also be found in unaffected individuals. Biallelic CNTNAP2 variants are rarer and cause a well-defined genetic syndrome known as CASPR2 deficiency disorder, a condition characterised by ID, early-onset refractory epilepsy, language impairment, and autistic features. A 7-year-old boy presented with hyperkinetic stereotyped movements that started during early infancy and persisted over childhood. Abnormal movements consisted of rhythmic and repetitive shaking of the four limbs, with evident stereotypic features. Additional clinical features included ID, attention deficit-hyperactivity disorder (ADHD), ASD, and speech impairment, consistent with CASPR2 deficiency disorder. Whole-genome array comparative genomic hybridization detected a maternally inherited 0.402 Mb duplication, which involved intron 1, exon 2, and intron 2 of CNTNAP2 (c.97 +?_209-?dup). The affected region in intron 1 contains a binding site for the transcription factor FOXP2, potentially leading to abnormal CNTNAP2 expression regulation. Sanger sequencing of the coding region of CNTNAP2 also identified a paternally-inherited missense variant c.2752C > T, p.(Leu918Phe). This case expands the molecular and phenotypic spectrum of CASPR2 deficiency disorder, suggesting that Hyperkinetic stereotyped movements may be a rare, yet significant, clinical feature of this complex neurological disorder. Furthermore, the identification of an in-frame, largely non-coding duplication in CNTNAP2 points to a sophisticated underlying molecular mechanism, likely involving impaired FOXP2 binding. The online version contains supplementary material available at 10.1186/s13052-021-01162-w.
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影响因子：
4.5
作者：
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通讯作者：
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DOI：
10.1073/pnas.1423205112
发表时间：
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影响因子：
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作者：
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DOI：
10.1056/nejmoa0802828
发表时间：
2008-11-27
期刊：
The New England journal of medicine
影响因子：
--
作者：
Vernes SC;Newbury DF;Abrahams BS;Winchester L;Nicod J;Groszer M;Alarcón M;Oliver PL;Davies KE;Geschwind DH;Monaco AP;Fisher SE
通讯作者：
Fisher SE