查看更多>>摘要：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 2 300 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.
查看更多>>摘要：目的 应用多种遗传学检测技术对1个额外标记染色体(sSMC)所致过度生长综合征家系进行遗传学分析，明确其致病原因，探讨sSMC的起源及重组形式。 方法 选取2021年8月31日于嘉兴市妇幼保健院就诊的1个过度生长综合征家系为研究对象，应用染色体核型分析、单核苷酸多态性微阵列(SNP array)及荧光原位杂交(FISH)技术，对该家系各成员进行染色体鉴定。 结果 结合染色体核型分析、SNP array及FISH检测结果，先证者及其妹妹的核型为47，XX，+neo(15)(qter→q25.3：)mat，其母亲的核型为47，XX，del(15)(q25.3：)，+neo(15)(qter→q25.3：)，其父亲的核型未见异常。 结论 联合多种遗传学检测技术可鉴定sSMC的来源，为遗传咨询提供可靠的依据。 Objective To carry out genetic analysis for a Chinese pedigree affected with intellectual disability and overgrowth due to a supernumerary marker chromosome (sSMC). Methods A pedigree which had presented at Jiaxing Maternity and Child Health Care Hospital on August 31, 2021 was selected as the study subject, for which chromosomal karyotyping, single nucleotide polymorphism-based microarray (SNP-array), and fluorescence in situ hybridization (FISH) were carried out in combination. Results SNP-array analysis showed that the proband and his sister had both harbored a 16.1 Mb duplication which encompassed the critical region of 15q26 overgrowth syndrome. FISH confirmed that the proband was 47, XX, + neo(15)(qter→q25.3: )mat, her mother was 47, XX, del(15)(q25.3: ), + neo(15)(qter→q25.3: ), whilst her father was normal. Conclusion Application of multiple genetic techniques has facilitated delineation of the origin of sSMC and reliable genetic counseling for this pedigree.
查看更多>>摘要：目的 探讨1例罕见的Y染色体重排致性发育异常(DSD)患者的遗传学病因。 方法 选取2018年5月2日因"身材矮小，第二性征发育不良"就诊于郑州大学第一附属医院的1例性发育异常女性患儿作为研究对象，收集患儿的临床资料。联合应用染色体G显带核型分析、SRY基因检测、全外显子测序(WES)、低深度全基因组测序拷贝数变异分析技术(CNV-seq)、荧光原位杂交技术(FISH)、全基因组测序(WGS)对患者进行遗传学检测。患儿遗传学特征明确后，给予相应治疗。 结果 患儿年龄为14岁，社会性别为女性，身材矮小，毛发旺盛，皮肤粗糙。外周血染色体核型为46，XY，且携带SRY基因。WES未检测到相关基因的致病性变异，但发现Yp11.32q12处存在59.37Mb重复。CNV-seq结果为47，XYY，外周血FISH结果提示患者为双着丝粒Y染色体嵌合体携带者，WGS发现Yp11.32q11.223存在大小为23.66 Mb的重复，同时Yq11.223q11.23存在约5.16 Mb的缺失，断裂点位于chrY：23656267。综合分析，患者的染色体核型应为46，X，psu idic(Y)(q11.223)[87]/46，X，del(Y)(q11.223)[13]。手术探查结果示性腺器官为卵巢组织，激素替代治疗后患儿有月经来潮，第二性征发育良好。 结论 联合多种遗传学检测明确了患儿的遗传学病因，为患儿的诊断及治疗提供了帮助。 Objective To explore the genetic basis for a rare case with Disorder of sex development. Methods Clinical data of the patient was collected. Chromosomal karyotyping, SRY gene testing, whole exome sequencing (WES), low-coverage massively parallel copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and whole genome sequencing (WGS) were carried out. Results The patient, a 14-year-old female, had manifested short stature and dysplasia of second sex characteristics. She was found to have a 46, XY karyotype and positive for the SRY gene. No pathogenic variant was found by WES, except a duplication at Yp11.32q12. The result of CNV-seq was 47, XYY. FISH has confirmed mosaicism for a dicentric Y chromosome. A 23.66 Mb duplication on Yp11.32q11.223 and a 5.16 Mb deletion on Yq11.223q11.23 were found by WGS. The breakpoint was mapped at chrY: 23656267. The patient′s karyotype was ultimately determined as 46, X, psu idic(Y)(q11.223)/46, X, del(Y)(q11.223). Conclusion The combination of multiple methods has facilitated clarification of the genetic etiology in this patient, which has provided a reference for the clinical diagnosis and treatment.
查看更多>>摘要：遗传性胆红素代谢障碍性疾病是导致黄疸的重要原因，其种类多样且临床表现相似，较难明确病因。近年来二代测序技术的应用揭示了越来越多与黄疸发生有关的遗传学病因。本文就胆红素代谢障碍性黄疸的临床表型和遗传学病因进行综述，以加强对于这类疾病的认识，扩展临床诊疗思路，同时为这类疾病患者及家系的遗传咨询和产前诊断提供参考。 Hereditary bilirubin metabolic disorder is an important cause for jaundice. For its diverse types and similar clinical manifestations, it has been difficult to make a clear etiological diagnosis. The application of next generation sequencing in recent years has delineated the more and more genetic etiologies for jaundice. This article has reviewed the clinical manifestations and genetic etiology of bilirubin metabolic disorder jaundice, with an aim to enhance the understanding of such diseases and facilitate their clinical diagnosis and treatment, which will provide a reference for genetic counseling and/or prenatal diagnosis for the affected individuals and families.
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