目的 总结报道1例智力障碍伴或不伴周围神经病（intellectual developmental disorder with or without peripheral neuropathy，IDDPN）患儿的临床特点和基因核苷二磷酸连接片段X型基序2（nucleoside diphosphate linked moiety X- type motif 2，NUDT2）的致病变异。 方法 采用回顾性分析，对2023年4月就诊于天津市儿童医院康复医学科的1例IDDPN患儿临床资料进行总结，并对现有报道NUDT2变异所致IDDPN患儿的临床表型与其基因突变谱的关系进行分析。 结果 本例患儿全面发育迟缓，面容特殊，四肢肌张力减退，伴有周围神经损害，全外显子测序发现患儿携带NUDT2基因的一个纯合突变c.34C>T（p.R12X）为无义突变。Sanger法验证，父母双方均为c.34C>T杂合子突变携带者。纳入国外已报道的10例IDDPN患者，发现导致发病的均为纯合突变，临床表型均有不同程度的认知障碍、运动障碍，其中3例合并周围神经损害。 结论 本例患儿低出生体质量/身长，婴儿期吸吮无力，肌张力减退，全面发育迟缓伴周围神经损害，基因检测提示NUDT2基因的纯合无义突变，诊断为IDDPN，为临床对该病的认识提供证据支持。 Objective To summarize the clinical characteristics and pathogenic mutation of gene NUDT2 in the child with intellectual disability with or without peripheral neuropathy (IDDPN). Methods The clinical characteristics and development of one child attending the Department of Rehabilitation of Tianjin Children's Hospital were evaluated retrospectively,and the relationship between the clinical phenotype and gene mutation profile of NUDT2 was analyzed. Results The child had global developmental delay, special appearance, low muscle tone of the limbs, accompanied by peripheral nerve damage in the limbs, and whole exome sequencing found that the child carried a homozygous mutation of NUDT2 gene, c.34C>T (p.R12X), which was a nonsense mutation. Sanger verified that both parents were carriers of c.34C>T heterozygous mutations. In the inclusion of 10 registered IDDPN patients, it was found that all of them were homozygous mutations, and the clinical phenotypes all had different degrees of cognitive impairment and movement disorders, among which only 3 cases were complicated by peripheral nerve damage. Conclusions The child in this case had low birth weight/length, weak sucking ability in infancy, cognitive impairment, peripheral nerve damage, and genetic testing showed homozygous nonsense mutation of NUDT2 gene, which provided evidence support for the clinical understanding of the disease.
Abstract
Objective To summarize the clinical characteristics and pathogenic mutation of gene NUDT2 in the child with intellectual disability with or without peripheral neuropathy (IDDPN). Methods The clinical characteristics and development of one child attending the Department of Rehabilitation of Tianjin Children's Hospital were evaluated retrospectively,and the relationship between the clinical phenotype and gene mutation profile of NUDT2 was analyzed. Results The child had global developmental delay, special appearance, low muscle tone of the limbs, accompanied by peripheral nerve damage in the limbs, and whole exome sequencing found that the child carried a homozygous mutation of NUDT2 gene, c.34C>T (p.R12X), which was a nonsense mutation. Sanger verified that both parents were carriers of c.34C>T heterozygous mutations. In the inclusion of 10 registered IDDPN patients, it was found that all of them were homozygous mutations, and the clinical phenotypes all had different degrees of cognitive impairment and movement disorders, among which only 3 cases were complicated by peripheral nerve damage. Conclusions The child in this case had low birth weight/length, weak sucking ability in infancy, cognitive impairment, peripheral nerve damage, and genetic testing showed homozygous nonsense mutation of NUDT2 gene, which provided evidence support for the clinical understanding of the disease.
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