Yue Ling, Jin Mei, Wang Xin, Wang Jing, Chen Ling, Jia Rong, Yang Zuozhen, Yang Fan, Li Jingman, Chen Cuiying, Zheng Huacheng, Yang Huafang
Department of Neurological Rehabilitation, Children's Hospital of Hebei Province, Hebei, China.
Electrophysiology Room, Children's Hospital of Hebei Province, Hebei, China.
Front Pediatr. 2022 Mar 4;10:806752. doi: 10.3389/fped.2022.806752. eCollection 2022.
Alkuraya-Kučinskas syndrome is an autosomal recessive disorder characterized by brain abnormalities associated with cerebral parenchymal underdevelopment, arthrogryposis, club foot, and global developmental delay. Most reported cases were cases of premature termination of pregnancies or neonatal deaths. To date, limited studies of nine surviving patients with global developmental delay and intellectual disability have been reported. In this study, we report another surviving patient.
Whole-exome sequencing was utilized for the proband, and variants were filtered, annotated, and classified. Candidate variants were validated by Sanger sequencing of the proband and his family. The literature was reviewed; the prognosis among different regions and the variant type was analyzed.
A non-synonymous variant [NM_015312.3: exon29: c.4892C>G (p.Pro1631Arg)] was identified and validated in the patient's father. A frameshift duplication [NM_015312.3: exon62: c.10872dupA (p.Arg3625Lysfs5)] that caused early translation termination was identified in his mother. The literature was reviewed, variants were classified into three regions of KIAA1109, and their survival status was summarized.
We reported another survival proband with Alkuraya-Kučinskas syndrome driven by KIAA1109. Our case expands the genotypic spectrum of Alkuraya-Kučinskas syndrome and explored the relationship between the variant region and survival.
Alkuraya-Kučinskas综合征是一种常染色体隐性疾病，其特征为与脑实质发育不全相关的脑部异常、关节挛缩、马蹄内翻足和全面发育迟缓。大多数已报道的病例为妊娠终止或新生儿死亡。迄今为止，仅有关于9例存活的全面发育迟缓和智力残疾患者的有限研究报道。在本研究中，我们报告了另一例存活患者。
对先证者进行全外显子组测序，对变异进行过滤、注释和分类。通过对先证者及其家人进行Sanger测序验证候选变异。查阅文献，分析不同区域和变异类型的预后情况。
在患者父亲中鉴定并验证了一个非同义变异[NM_015312.3：外显子29：c.4892C>G（p.Pro1631Arg）]。在其母亲中鉴定出一个导致早期翻译终止的移码重复变异[NM_015312.3：外显子62：c.10872dupA（p.Arg3625Lysfs5）]。查阅文献，将变异分类到KIAA1109的三个区域，并总结了它们的存活状态。
我们报告了另一例由KIAA1109驱动的Alkuraya-Kučinskas综合征存活先证者。我们的病例扩展了Alkuraya-Kučinskas综合征的基因型谱，并探索了变异区域与存活之间的关系。
