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ENGLISH ABSTRACT
WDR62基因变异致原发性小头畸形1例
余丽华
王兴旺
刘玲
曾玉坤
齐一鸣
黄演林
丁红珂
作者及单位信息
·
DOI： 10.3760/cma.j.cn511374-20211201-00951
A case of primary microcephaly associated with compound heterozygous variants of WDR62 gene
Yu Lihua
Wang Xingwang
Liu Ling
Zeng Yukun
Qi Yiming
Huang Yanlin
Ding Hongke
Authors Info & Affiliations
Yu Lihua
Medical Genetics Center of Guangdong Maternal and Child Health Care Hospital, Guangzhou, Guangdong 511442, China
Wang Xingwang
Medical Genetics Center of Guangdong Maternal and Child Health Care Hospital, Guangzhou, Guangdong 511442, China
Liu Ling
Medical Genetics Center of Guangdong Maternal and Child Health Care Hospital, Guangzhou, Guangdong 511442, China
Zeng Yukun
Medical Genetics Center of Guangdong Maternal and Child Health Care Hospital, Guangzhou, Guangdong 511442, China
Qi Yiming
Medical Genetics Center of Guangdong Maternal and Child Health Care Hospital, Guangzhou, Guangdong 511442, China
Huang Yanlin
Medical Genetics Center of Guangdong Maternal and Child Health Care Hospital, Guangzhou, Guangdong 511442, China
Ding Hongke
Medical Genetics Center of Guangdong Maternal and Child Health Care Hospital, Guangzhou, Guangdong 511442, China
·
DOI： 10.3760/cma.j.cn511374-20211201-00951
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摘要

目的对1例原发性小头畸形、生长发育落后的患儿进行基因变异分析。

方法以1例因发育落后于2020年10月来广东省妇幼保健院就诊的女性患儿作为研究对象。采集患儿及其父母的外周血样，对其进行全外显子组测序检测，并用Sanger测序对候选变异进行家系验证。本研究通过了广东省妇幼保健院医学伦理委员会的审查(批准号：202201278)。

结果基因检测发现患儿携带 WDR62基因c.2963delC(p.Pro988Argfs*80)和c.3163G>T(p.Glu1055*)复合杂合变异，分别来源于其父亲和母亲。前者位于第24外显子，为缺失移码变异，后者位于第26外显子，为无义变异，均可能导致蛋白质翻译提前终止。根据美国医学遗传学和基因组学学会(ACMG)相关指南均评级为可能致病性。

结论结合患儿的临床表现、变异位点的致病性及家系分析，判断上述变异为患儿的遗传学病因。上述发现丰富了常染色体隐性遗传性原发性小头畸形2型的突变谱，也为该家系再次妊娠的产前诊断提供了线索。

原发性小头畸形2型;生长发育落后; WDR62基因 ;变异
ABSTRACT

ObjectiveTo explore the genetic basis for a girl with primary microcephaly and growth retardation.

MethodsA girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278).

ResultsDNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c. 2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene.

ConclusionBased on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.

Primary microcephaly type 2;Growth retardation; WDR62 gene variant
Ding Hongke, Email: mocdef.qabq5120029
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引用本文

余丽华,王兴旺,刘玲,等. WDR62基因变异致原发性小头畸形1例 [J]. 中华医学遗传学杂志,2025,42(02)：175-179.

DOI:10.3760/cma.j.cn511374-20211201-00951

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原发性小头畸形2型(primary microcephaly-2，MCPH2)是一种常染色体隐性遗传性神经发育障碍性疾病，以原发性小头畸形、轻至重度精神发育落后为主要特征。患者的临床表型高度可变，表现为：①头围从略低于正常到严重落后(-6.0 SD ～ -9.0 SD)；②可伴有各种类型的皮质畸形如巨脑回、皮质增厚、无脑畸形、胼胝体发育不全、脑裂畸形等；③伴或不伴癫痫发作 [ 1 , 2 , 3 , 4 ]。 WDR62基因的变异与伴或不伴皮质畸形的原发性小头畸形2型(OMIM #604317)密切相关，该基因目前被公认为导致小头畸形的第二常见因素。
既往国外报道与 WDR62基因变异相关的MCPH2案例较少，国内亦仅见2例报道，其中1例为本中心确诊的病例 [ 2 , 5 ]。本研究应用二代测序(next generation sequencing，NGS)技术对1例表现为小头畸形、生长发育落后的女性患儿进行了分析，其结果扩展了 WDR62基因的变异谱，为遗传咨询提供了线索。
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参考文献
[1]
Nicholas AK , Khurshid M , Désir J ,et al. WDR62 is associated with the spindle pole and is mutated in human microcephaly [J]. Nat Genet, 2010,42(11):1010-1014. DOI: 10.1038/ng.682 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Banerjee S , Chen H , Huang H ,et al. Novel mutations c．28G > T (p.Ala10Ser) and c．189G > T (p.Glu63Asp) in WDR62 associated with early onset acanthosis and hyperkeratosis in a patient with autosomal recessive microcephaly type 2 [J]. Oncotarget, 2016,7(48):78363-78371. DOI: 10.18632/oncotarget.13279 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Kousar R , Hassan MJ , Khan B ,et al. Mutations in WDR62 gene in Pakistani families with autosomal recessive primary microcephaly [J]. BMC Neurol, 2011,11:119. DOI: 10.1186/1471-2377-11-119 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Bhat V , Girimaji SC , Mohan G ,et al. Mutations in WDR62 , encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations [J]. Clin Genet, 2011,80(6):532-540. DOI: 10.1111/j.1399-0004.2011.01686.x .
返回引文位置Google Scholar
百度学术
万方数据
[5]
余丽华，丁红珂，周伟宁，等. 国内第二例 WDR62 基因复合杂合突变导致的小头畸形病例报道 [J]. 中国产前诊断杂志(电子版), 2018,10(3):53-56. DOI: 10.13470/j.cnki.cjpd.2018.03.013 .
返回引文位置Google Scholar
百度学术
万方数据
Yu LH , Ding HK , Zhou WN ,et al. The second case of primary microcephaly associated with compound heterozygous variants in WDR62 gene in China [J]. Chin J Prenat Diagn (Electronic Version), 2018,10(3):53-56. DOI: 10.13470/j.cnki.cjpd.2018.03.013 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[6]
Melinda Z , Tibor K , Nikoletta N ,et al. A novel WDR62 missense mutation in microcephaly with abnormal cortical architecture and review of the literature [J]. J Appl Genet, 2019,60(2):151-162. DOI: 10.1007/s13353-019-00486-y .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Rosaria N , Antonina F , Vincenzo A ,et al. A novel mutation of WDR62 gene associated with severe phenotype including infantile spasm, microcephaly, and intellectual disability [J]. Brain Dev, 2018,40(1):58-64. DOI: 10.1016/j.braindev.2017.07.003 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Imane C , Abdelali Z , Wafaa J ,et al. A novel non sense mutation in WDR62 causes autosomal recessive primary microcephaly: a case report [J]. BMC Med Genet, 2018,19(1):118. 10.1186/s12881-018-0625-6 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Muhammad I , Mahmood R , Sameera S ,et al. A novel WDR62 mutation causes primary microcephaly in a large consanguineous Saudi family [J]. Ann Saudi Med, 2017,37(2):148-153. DOI: 10.5144/0256-4947.2017.148 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Muhammad I , Mahmood R , Angham A ,et al. Novel compound heterozygous mutations in WDR62 gene leading to developmental delay and primary microcephaly in Saudi Family [J]. Pak J Med Sci, 2019,35(3):764-770. DOI: 10.12669/pjms.35.3.36 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
Sajida R , Jamshaid M , Abubakar M ,et al. An update of pathogenic variants in ASPM, WDR62, CDK5RAP2, STIL, CENPJ , and CEP135 underlying autosomal recessive primary microcephaly in 32 consanguineous families from Pakistan [J]. Mol Genet Genomic Med, 2020,8(9):e1408. DOI: 10.1002/mgg3.1408 .
返回引文位置Google Scholar
百度学术
万方数据
[12]
Ryszard S , Robert S , Ewa O ,et al. Further delineation of phenotype and genotype of Primary microcephaly syndrome with cortical malformations associated with mutations in the WDR62 gene [J]. Genes (Basel), 2021,12(4):594. DOI: 10.3390/genes12040594 .
返回引文位置Google Scholar
百度学术
万方数据
[13]
You G , Dong-Woo L , Jaewon K ,et al. Two novel mutations (c.883-4_890del and c．1684C > G) of WDR62 gene associated with autosomal recessive primary microcephaly: a case report [J]. Front Pediatr, 2019,7:457. DOI: 10.3389/fped.2019.00457 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
丁红珂，Email： mocdef.qabq5120029
B

余丽华：研究选题、实验设计、实施研究、采集和分析数据、获取研究经费、撰写论文；王兴旺：研究选题；刘玲：实施研究、分析数据；曾玉坤：研究选题、实施研究、采集数据；齐一鸣：实验设计、数据分析、获取研究经费；黄演林：数据分析、获取研究经费；丁红珂：对文章的知识性内容作审阅、获取研究经费

C
所有作者均声明不存在利益冲突
D
广东省医学科学技术研究基金 (A2020302、B2021258)
广东省科技计划 (2021A1414020008)
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