中国先天性小头畸形(CM)的遗传景观数据很少,在中国,由最常见的突变基因ASPM引起的CM的发病率仍然未知。
纳入2016年8月1日至2020年8月31日在复旦大学附属儿童医院住院的61例CM新生儿,并对临床数据和临床外显子组测序数据进行分析。从中国儿童基因检测临床协作系统数据库中收集了另外18,103份父母数据条目,通过分析ASPM突变的载波频率来估计中国华东地区ASPM相关先天性小头畸形(ASPM-CM)的发病率。
在61例CM新生儿中,35例(57.4%)患者被确定为遗传结果,包括24例单核苷酸变异(SNV)患者和11例拷贝数变异(CNV)患者。ASPM是3例患者中检测到的最常见的具有有害SNV的基因。有遗传发现的患者表现出明显较高的发育迟缓发生率(91.3%,21/23)比没有遗传发现的人(60%,9/15)(p=0.04)。所有3例下降的患者都有遗传发现。华东地区ASPM-CM发病率估计为1/1,295,044。
全面的基因检测,同时检测SNV和CNV,建议新生儿CM。有遗传发现的患者应该意识到发育迟缓的可能性。ASPM基因缺陷是本研究中CM最常见的遗传原因。对华东地区ASPM-CM发病率的估算可为分析总体发病率提供参考。
Data on the genetic landscape of congenital microcephaly (CM) in
China are scarce, and the incidence of CM caused by the most commonly mutated gene ASPM in
China remains unknown.
Sixty-one neonates with CM who were hospitalized in the Children\'s Hospital of Fudan University between August 1, 2016, and August 31, 2020, were enrolled, and the clinical data and clinical exome-sequencing data were analyzed. An additional 18,103 parental data entries from the Chinese Children\'s Genetic Testing Clinical Collaboration System database were collected to estimate the incidence of ASPM-related congenital microcephaly (ASPM-CM) in East
China by analyzing the carrier frequency of ASPM mutations.
Among the 61 neonates with CM, 35 (57.4%) patients were identified with genetic findings, including 24 patients with single nucleotide variants (SNVs) and 11 patients with copy number variations (CNVs). ASPM was the most common gene with detrimental SNVs detected in 3 patients. Patients with genetic findings showed a significantly higher incidence of developmental delay (91.3%, 21/23) than those without genetic findings (60%, 9/15) (p = 0.04). All the 3 decreased patients had genetic findings. The estimated ASPM-CM incidence in East
China was 1/1,295,044.
Comprehensive genetic testing, detecting both SNVs and CNVs, is recommended for newborns with CM. Patients with genetic findings should be aware of the potential for developmental delay. ASPM gene defect was the most common genetic cause of CM in this study. The estimation of the incidence of ASPM-CM in East
China might provide a reference for analyzing overall incidence.