UF de Génétique Médicale et CRMR « Déficience intellectuelle », Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, APHP Sorbonne Université, Paris, France.
Service de Neurologie Pédiatrique, Hôpital Armand Trousseau, APHP Sorbonne Université, Paris, France.
Genet Med. 2020 Nov;22(11):1887-1891. doi: 10.1038/s41436-020-0872-8. Epub 2020 Jun 22.
Abnormality of the corpus callosum (AbnCC) is etiologically a heterogeneous condition and the prognosis in prenatally diagnosed cases is difficult to predict. The purpose of our research was to establish the diagnostic yield using chromosomal microarray (CMA) and exome sequencing (ES) in cases with prenatally diagnosed isolated (iAbnCC) and nonisolated AbnCC (niAbnCC).
CMA and prenatal trio ES (pES) were done on 65 fetuses with iAbnCC and niAbnCC. Only pathogenic gene variants known to be associated with AbnCC and/or intellectual disability were considered.
pES results were available within a median of 21.5 days (9-53 days). A pathogenic single-nucleotide variant (SNV) was identified in 12 cases (18%) and a pathogenic CNV was identified in 3 cases (4.5%). Thus, the genetic etiology was determined in 23% of cases. In all diagnosed cases, the results provided sufficient information regarding the neurodevelopmental prognosis and helped the parents to make an informed decision regarding the outcome of the pregnancy.
Our results show the significant diagnostic and prognostic contribution of CMA and pES in cases with prenatally diagnosed AbnCC. Further prospective cohort studies with long-term follow-up of the born children will be needed to provide accurate prenatal counseling after a negative pES result.
胼胝体异常（AbnCC）在病因学上是一种异质性疾病，产前诊断病例的预后很难预测。我们研究的目的是在产前诊断孤立性（iAbnCC）和非孤立性 AbnCC（niAbnCC）病例中，通过染色体微阵列（CMA）和外显子组测序（ES）来确定诊断的效果。
对 65 例 iAbnCC 和 niAbnCC 胎儿进行了 CMA 和产前三联体 ES（pES）检测。只考虑了已知与 AbnCC 和/或智力障碍相关的致病基因突变。
pES 结果的中位时间为 21.5 天（9-53 天）。在 12 例（18%）中发现了致病性单核苷酸变异（SNV），在 3 例（4.5%）中发现了致病性 CNV。因此，23%的病例确定了遗传病因。在所有诊断病例中，结果提供了足够的关于神经发育预后的信息，并帮助父母对妊娠结局做出明智的决定。
我们的结果表明，CMA 和 pES 在产前诊断 AbnCC 病例中具有重要的诊断和预后作用。需要进一步进行前瞻性队列研究，并对出生后的儿童进行长期随访，以便在 pES 结果为阴性时提供准确的产前咨询。
