20p母源性单亲二体患儿1例的临床及遗传学分析

Clinical and genetic analysis of a child with maternal uniparental disomy of chromosome 20

目的探讨一例20号染色体母源性单亲二倍体(UPD(20)mat)患儿的临床及遗传学特点。方法分析华中科技大学同济医学院附属同济医院儿科2021年4月8日确诊的1例UPD(20)mat患儿的临床表型和内分泌水平;对患儿进行全外显子组测序(whole exome sequencing,WES)。对候选变异进行Sanger测序家系验证。用甲基化特异的多重连接探针扩增(methylation-specific multiplex ligation-dependent probe amplification,MS-MLPA)检测STX16/GNAS-AS1/GNAS等区域的基因拷贝数变化及甲基化状态,并复习相关文献。结果先证者外貌无特殊,表现为通贯掌、生后喂养困难、生长迟缓、身材矮小、注意缺陷与多动障碍、轻度智力低下、言语和语言发育障碍、语音障碍。胰岛素样生长因子-1水平低。染色体核型未见异常,经WES分析、Sanger测序验证和MS-MLPA检测提示,患儿为UPD(20)mat。结论UPD(20)mat常见的临床表型为喂养困难、生长迟缓、身材矮小,可伴随注意缺陷与多动障碍、言语和语言发育障碍、内分泌激素的紊乱,需长期随访。对于有上述临床表型的高龄母亲,应尽早进行基因检测和遗传咨询。

Objective To explore the clinical and genetic characteristics of a boy with isolated maternal uniparental disomy of chromosome 20[UPD(20)mat].Methods A child who was admitted to the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology on April 8,2021.was selected as the study subject.Phenotypic and endocrinological findings of the child were retrospectively analyzed.Whole exome sequencing(WES)and methylation-specific multiplex ligation-dependent probe amplification(MS-MLPA)were carried out for detecting the UPD sequences and copy number variations.Both of his parents were verified by Sanger sequencing.Relevant literature was systematically reviewed.Results The child,a 3-year-and-8-month-old boy born to a 41-year-old mother by Cesarean delivery at 36+2 gestational weeks due to oligohydramia,had a birth weight of 2300 g and length of 46 cm.He was admitted to the NICU for feeding difficulties which had persisted despite of clinical management.At the age of 3.75,he had a height of 92.5 cm(<3rd percentile;25th~50th percentile at 2.5 years)and a weight of 10.8 kg(<3rd percentile;50th percentile at 15 months).He had also presented with growth retardation,short stature,attention deficit and hyperactivity disorder(ADHD),mild mental retardation,and speech and language development disorders.He had simian creases in both hands but no additional dysmorphic signs,and his motor development was normal.Serum insulin,thyroid-stimulating hormone,and insulin growth factor binding protein 3 levels were within the normal ranges,though insulin growth factor-1(IGF-1)was slightly decreased.Since that time he had continuously used atomoxetine hydrochloride capsules to control his ADHD.WES and MS-MLPA revealed the existence of UPD(20)mat.Conclusion The UPD(20)mat syndrome is characterized by feeding difficulties,growth retardation and short stature.The child in our case has been accompanied by ADHD and speech and language development disorders,which required long-term treatment.For women with advanced maternal age and suggestive phenotypes,genetic testing and counseling should be conducted.