Data Sheet 2_Case Report: Identification of a novel hemizygous missense RPL10 gene variant in two unrelated patients.xlsx

The X-linked syndromic intellectual developmental disorder-35 (MRXS35; OMIM#300998) is caused by variants in the RPL10 gene (OMIM*312173) on chromosome Xq28. Patients with MRXS35 mainly present with intellectual disability (ID), psychomotor development delay, speech delay, short stature, craniofacial anomalies, hypotonia, seizures, gastrointestinal problems, genitourinary anomalies, cardiac anomalies, eye defects, and hearing loss. Herein, we are the first to report two unrelated Chinese patients with the same novel hemizygous missense RPL10 gene variant. Two male patients from two different families were admitted to the hospital for genetic counseling. In the first months of life, both newborns presented with congenital laryngeal stridor, feeding difficulties, neonatal pneumonia, neonatal hypoglycemia, dysmorphic features, and bilateral cryptorchidism. At his last clinical evaluation at 9 years of age, case II presented with ID, speech delay, short stature, and craniofacial anomalies. Whole-exome sequencing identified the same hemizygous missense RPL10 gene variant (NM_006013.5:c.347G>A, p.Arg116Gln) in each patient, inherited from their respective mothers. The functional analysis of this variant in vitro demonstrated that this missense RPL10 gene variant (c.347G>A) reduced the mRNA expression of the RPL10 gene, thereby decreasing synthesis of the RPL10 protein. Our in vitro functional analysis indicated a loss-of-function effect of RPL10 gene variants.

X连锁综合征性智力发育障碍35型（X-linked syndromic intellectual developmental disorder-35, MRXS35；OMIM#300998）由X染色体Xq28区域的RPL10基因（OMIM*312173）变异所导致。MRXS35患者主要表现为智力障碍（intellectual disability, ID）、精神运动发育迟缓、语言发育迟缓、身材矮小、颅面畸形、肌张力低下、癫痫发作、胃肠道病症、泌尿生殖系统异常、心脏异常、眼部缺陷及听力损失。本研究首次报道2例无亲缘关系的中国患者，二者均携带同一新型半合子错义RPL10基因变异。2例来自不同家系的男性患者因遗传咨询入院。出生后数月内，两名新生儿均出现先天性喉喘鸣、喂养困难、新生儿肺炎、新生儿低血糖、畸形特征及双侧隐睾。在9岁时的末次临床评估中，病例II表现为智力障碍、语言发育迟缓、身材矮小及颅面畸形。全外显子测序在两名患者体内均检测到同一半合子错义RPL10基因变异（NM_006013.5:c.347G>A, p.Arg116Gln），该变异均源自其各自母亲。体外针对该变异的功能分析显示，此错义RPL10基因变异（c.347G>A）可降低RPL10基因的mRNA表达水平，进而减少RPL10蛋白的合成。本研究的体外功能分析结果表明，RPL10基因变异存在功能丧失效应。