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中华医学遗传学杂志
四川大学
中华医学遗传学杂志

四川大学

张思仲

双月刊

1003-9406

cjmg@cma.org.cn

028-85501165

610041

四川省成都市人民南路三段17号(四川大学华西校区)

中华医学遗传学杂志/Journal Chinese Journal of Medical GeneticsCSCD北大核心CSTPCD
查看更多>>中华医学会主办，四川大学承办。本刊以报道我国医学遗传学、人类遗传学和相关领域的基础理论、技术方法等最新研究成果；以从事医学遗传学工作的各科临床医生、计划生育工作者、大专院校和科研单位有关人员为主要读者对象。设有述评、论著、技术与方法、综述、调查报告、遗传咨询、临床细胞遗传学、病例报告等栏目。 从1998年以来被美国《医学索引》（IM）、《化学文摘》（CA）、《工程索引》（EI）、ISI数据库的Biological Abstracts及BIOSIS Previews，波兰《哥白尼索引》（IC）,荷兰《医学文摘》（EM）和俄罗斯《文摘杂志》（AJ）等国际著名检索系统收录。
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    孤立型室间隔缺损胎儿的基因组拷贝数变异分析及文献回顾

    时盼来侯雅勤陈铎夏艳洁...
    317-321页
    查看更多>>摘要：目的 评估拷贝数变异(CNVs)检测对于孤立型室间隔缺损(VSD)胎儿遗传学病因的诊断价值。 方法 选取2017年12月至2020年12月郑州大学第一附属医院超声检查发现的69例孤立型VSD胎儿，同时检索万方、万方医学、中国知网等数据库，2016年1月1日至2021年1月1日以"室间隔缺损""拷贝数变异"以及"产前"为关键词，连同文献报道的839例胎儿，共计908例孤立型VSD胎儿作为研究对象。对69例胎儿进行低深度全基因组测序，并合并文献数据进行回顾性分析。 结果 在908例样本中，共检出33例致病性异常，总体检出率为3.63%。其中包括11例(1.21%)非整倍体以及22例(2.42%)致病性CNVs。后者涉及12种综合征，具体包括5例22q11.21缺失、2例4q末端缺失以及1例9q亚端粒缺失，均与心脏发育相关。22例致病性CNVs胎儿中，15例具有已知的妊娠结局，12例为自主终止妊娠，3例出生后室间隔自然闭合，但其中1例具有其他异常。 结论 孤立型VSD的胎儿具有较高的染色体异常检出率，因此建议对其进行CNV-seq检测。 Objective To assess the value of copy number variation sequencing (CNV-seq) for revealing the genetic etiology of fetuses with isolated ventricular septal defect (VSD). Methods From December 2017 to December 2020, 69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University. Meanwhile, 839 similar prenatal cases were selected from public databases including Wanfang data, Wanfang Medicine, and China National Knowledge Infrastructure (CNKI) by using keywords such as "Ventricular septal defect", "Copy number variation", and "Prenatal". A total of 908 fetuses with isolated VSD were analyzed. CNV-seq was carried out for 69 fetuses. Results Among the 908 fetuses, 33 (3.63%) were found to harbor pathogenic CNVs, which included 11 chromosomal aneuploidies (1.21%) and 22 pathogenic CNVs (2.42%). The pathogenic CNVs have involved 12 genetic syndromes, with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome, 2 cases of 4q terminal deletion syndrome, and 1 case of 9q subtelomere deletion syndrome. The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known, of which 12 were terminated, and 3 had spontaneous closure of the ventricular septum after birth, but 1 of them had other abnormalities. Conclusion Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities, for which CNV-seq should be recommended.

    拷贝数变异孤立型室间隔缺损胎儿妊娠结局

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    IGSF1基因变异所致中枢性甲状腺功能低下4例患儿的临床特点及遗传学分析

    张陈晨陈临琪陈秀丽谢蓉蓉...
    322-327页
    查看更多>>摘要：目的 探讨IGSF1基因变异所致先天性中枢性甲状腺功能减退症患儿的临床表现及基因变异特点。 方法 回顾性分析4例2017年至2021年苏州大学附属儿童医院收治的4例患儿的临床资料、基因检测结果及随访数据。 结果 4例患儿均为男性。患儿1因新生儿期黄疸入院，患儿2、3因儿童期生长迟缓查甲状腺功能提示血清游离甲状腺素(FT4)稍低，患儿4在新生儿期发现FT4降低，基因检测发现4例患儿均携带IGSF1基因致病变异，且均遗传自母亲。给予患儿左旋甲状腺素口服并定期随访，复查甲状腺功能控制良好。 结论 IGSF1基因变异可导致先天性中枢性甲状腺功能减退，临床表现具有多样性，基因测序有助于早期确诊。 Objective To explore the clinical manifestations and genetic characteristics of patients with congenital central hypothyroidism due to variants of IGSF1 gene. Methods Clinical data, results of genetic testing, and follow-up of four patients admitted to Children′s Hospital of Soochow University during 2017 to 2021 were retrospectively analyzed. Results All of the four patients were males. Patient 1 had presented as neonatal jaundice, patients 2 and 3 were admitted for growth retardation during childhood, and thyroid function test indicated slightly low free thyroxine (FT4), patient 4 was found to have reduced FT4 in the neonatal period. Genetic testing revealed that all of the four patients have harbored pathogenic variants of the IGSF1 gene, which were all inherited from their mothers. The thyroid functions in all patients were well controlled with oral levothyroxine and regular follow-up. Conclusion Pathogenic variants of the IGSF1 gene probably underlay the congenital central hypothyroidism with a variety of clinical manifestations, and genetic testing can facilitate the diagnosis at an early stage.

    IGSF1基因先天性中枢性甲状腺功能低下基因型-表型对应关系

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    迟发型鸟氨酸氨甲酰转移酶缺乏症患儿4例的 OTC基因变异分析

    谢垒王瑶马威范晓蕾...
    328-331页
    查看更多>>摘要：目的 对4例迟发型鸟氨酸氨甲酰转移酶缺乏症(OTCD)患儿的临床特点及OTC基因变异进行分析。 方法 收集2020年1月至2021年4月收治于郑州大学第一附属医院儿童重症监护室的4例OTCD患儿的临床资料，抽取患儿及父母的外周血样，用高通量测序的方法进行全外显子组测序(WES)，对候选致病变异进行Sanger测序验证及生物信息学分析变异蛋白结构。 结果 4例患儿的临床表现主要包括呕吐、抽搐和意识障碍。WES结果显示患儿1的OTC基因第5外显子存在c.421C>T(p.R141X)变异。患儿2和3的OTC基因第2外显子均存在c.119G>A(p.R40H)变异。患儿4的OTC基因第5外显子存在c.607T>A (p.S203T)变异。c.607T>A变异既往未见报道，根据美国医学遗传学与基因组学学会变异相关指南，判定为可能致病性变异(PM1+PM2_Supporting+PP3+PP4)，蛋白结构预测显示该变异将造成氢键断裂。Sanger测序验证患儿2 ~ 4的变异均为母源性。 结论 OTC基因变异可能是4例迟发型OTCD患儿的遗传学病因。c.607T>A的发现丰富了OTC基因的变异谱。 Objective To analyze the clinical manifestation and genetic basis for four children with delayed onset ornithine transcarbamylase deficiency (OTCD). Methods Clinical data of 4 children with OTCD admitted to the Pediatric Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University from January 2020 to April 2021 were reviewed. Peripheral blood samples of the patients and their parents were collected and subjected to whole exome sequencing (WES). Bioinformatic analysis and Sanger sequencing verification were carried out to verify the candidate variants. Impact of the candidate variants on the protein structure was also predicted. Results The clinical manifestations of the 4 children included vomiting, convulsion and disturbance of consciousness. WES revealed that the child 1 was heterozygous for a c. 421C>T (p.R141X) variant in exon 5, children 2 and 3 were hemizygous for a c. 119G>A (p.R40H) variant in exon 2, and child 4 was hemizygous for a c. 607T>A (p.S203T) variant in exon 5 of theOTC gene. Among these, the c. 607T>A variant was unreported previously and predicted to be pathogenic (PM1+ PM2_Supporting+ PP3+ PP4). Bioinformatic analysis has predicted that the variant may result in breakage of hydrogen bonds and alter the protein structure and function. Sanger sequencing confirmed that the variants in children 2 to 4 have derived from their mothers. Conclusion The pathogenic variants of the OTC gene probably underlay the delayed OTCD in 4 children. The discovery of the c. 607T>A variant has enriched the mutational spectrum of theOTC gene.

    鸟氨酸氨甲酰转移酶缺乏症高氨血症血尿有机酸检测OTC基因

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    散发性颅骨锁骨发育不全2例的临床表型及基因变异分析

    袁莉敏刘灵翟闪闪李静...
    332-336页
    查看更多>>摘要：目的 探讨2例散发性颅骨锁骨发育不全(CCD)的临床表型及基因诊断。 方法 回顾性分析分别在2021年12月16日与2021年12月9日收治于郑州大学第三附属医院的2例CCD的临床资料，并对其进行全外显子组测序(WES)、染色体微阵列分析及拷贝数变异测序。 结果 胎儿1的产前表型主要包括胎儿颅骨钙化差、顶枕部膨隆、颅骨受压变形、鼻骨缺失等，患儿2在婴幼儿期的表现包括前囟门闭合延迟、反复呼吸道感染、体格发育落后等，影像学提示锁骨发育不全。WES测序发现二者分别携带RUNX2基因c.911_914delinsTTT杂合变异和c.1008delT杂合变异，均为新发变异。 结论 胎儿锁骨发育不全、颅骨钙化不足、鼻骨缺失是CCD患儿主要的产前超声表现。对于体格发育落后、反复呼吸道感染，锁骨发育不全的婴幼儿也应警惕本病，并通过遗传学检测协助诊断。RUNX 2基因的c.911_914delinsTTT和c.1008del致病变异的发现扩展了RUNX2基因的变异谱，为患儿家庭的遗传咨询和产前诊断奠定了基础。 Objective To explore the clinical phenotypes and genetic diagnosis of two cases of sporadic cleidocranial dysplasia. Methods The clinical data of two cases of CCD admitted to the Third Affiliated Hospital of Zhengzhou University on December 16, 2021 and December 9, 2021 were analyzed retrospectively, and the whole exome sequencing (WES), chromosome microarray analysis and copy number variation sequencing were performed. Results The main ultrasonographic findings of the fetus had included poorly calcified skull bones, budging of parieto-occipital area, compression and deformation of skull, and loss of nasal bone. The infant′s clinical phenotypes included delayed closure of anterior fontanelle, recurrent respiratory tract infection, growth retardation, and clavicular hypoplasia. By WES analysis, case 1 was detected with heterozygous variation of RUNX2 gene c. 911_914delinsTTT. Case 2 was detected with heterozygous c. 1008delT variant of RUNX2 gene. Both variants were verified by Sanger sequencing to have occurred de novo. Conclusion For sporadic cases featuring cleidocranial dysplasia, prenatal ultrasonography is particularly important. Hypoplastic clavicle, skull calcification and nasal bone absence are the main features. Diagnosis should also be suspected for infants featuring growth retardation, recurrent respiratory tract infections and clavicular dysplasia. Identification of c. 911_914delinsTTT and c. 1008delT in the RUNX2 gene has facilitated genetic counseling and prenatal diagnosis, and also expanded the mutational spectrum of RUNX2 gene.

    颅骨锁骨发育不全胎儿期婴幼儿期基因诊断RUNX2基因遗传咨询

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    FHL2基因变异致扩张型心肌病1例并文献回顾

    于春蕊贾丽娟郝婵娟左汴京...
    337-343页
    查看更多>>摘要：目的 探讨1例扩张型心肌病(DCM)患儿的临床表型及遗传学特征。 方法 收集2020年4月28日就诊于郑州儿童医院的1例患儿的临床资料，并对其进行家系全外显子组测序(trio-WES)，对候选变异进行Sanger测序验证。以"FHL2"作为关键词，检索1997年1月1日至2021年10月31日PubMed数据库收录的文献，同时在ClinVar数据库中检索FHL2变异作为补充支持，分析基因变异与临床特征的对应关系。 结果 患儿为女性，就诊时为5月龄，临床特征为左心室增大、收缩功能减低。基因测序发现其FHL2基因存在杂合错义变异c.391C>T(p.Arg131Cys)，其父母未携带相同的变异。根据美国医学遗传学与基因组学学会(ACMG)变异相关指南，c.391C>T(p.Arg131Cys)被升级为可能致病性变异(PS2+PM2_Supporting+PP3+PP5)。通过文献检索，共发现10例FHL2基因变异的患者，其中6例表现为DCM，2例表现为肥厚型心肌病(HCM)，2例表现为不明原因猝死(SUD)。变异位于FHL2蛋白LIM 3结构域的患者均表现为HCM，位于LIM 0 ~ 2、LIM 4结构域者则主要表现为DCM。 结论 FHL2基因杂合错义变异c.391C>T(p.Arg131Cys)可能是患儿DCM的原因。上述发现强调了trio-WES在疾病诊断和遗传咨询中的重要性。 Objective To explore the clinical phenotype and genetic features of a child with dilated cardiomyopathy (DCM). Methods Clinical data of the child who had presented at Zhengzhou Children′s Hospital on April 28, 2020 was collected. Trio-whole exome sequencing (trio-WES)was carried out for the child and her parents, and candidate variants were validated by Sanger sequencing. " FHL2" was taken as the key word to retrieve related literature from January 1, 1997 to October 31, 2021 in the PubMed database and was also searched in the ClinVar database as a supplement to analyze the correlation between genetic variants and clinical features. Results The patient was a 5-month-old female infant presented with left ventricular enlargement and reduced systolic function. A heterozygous missense variant c. 391C>T (p.Arg131Cys) inFHL2 gene was identified through trio-WES. The same variant was not detected in either of her parents. A total of ten patients with FHL2 gene variants have been reported by previous literature, six of them presented with DCM, two with hypertrophic cardiomyopathy (HCM), and two with sudden unexplained death (SUD). Phenotypic analysis revealed that patients with variants in the LIM 3 domain presented hypertrophic cardiomyopathy and those with variants of the LIM 0~2 and LIM 4 domains had mainly presented DCM. The c. 391C>T (p.Arg131Cys) has been identified in a child with DCM, though this variant has not been validated among the patient′s family members. Based on the guidelines of the American College of Medical Genetics and Genomics, the c. 391C>T(p.Arg131Cys) variant was re-classified as likely pathogenic (PS2+ PM2_Supporting+ PP3+ PP5). Conclusion The heterozygous missense variant of c. 391C>T (p.Arg131Cys) in theFHL2 gene probably predisposed to the DCM in this child, which has highlighted the importance of trio-WES in the clinical diagnosis and genetic counseling.

    扩张型心肌病FHL2基因全外显子组测序

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    SCN9A基因变异所致轻型癫痫1例的遗传学分析

    尹训强牛玉萍邹洋高媛...
    344-348页
    查看更多>>摘要：目的 探讨1例癫痫患者的遗传学病因，并为其提供遗传咨询。 方法 选取2020年11月11日因有生育需求来山东大学附属生殖医院就诊的1例癫痫患者作为研究对象，收集患者的病史，通过全外显子组测序(WES)筛选候选变异，并进行Sanger测序验证。通过反转录-PCR及Sanger测序确定候选变异的致病性。 结果 患者为35岁女性，发病时无发热，意识丧失且颞叶出现异常放电，以抽搐、昏厥为主。WES检测显示其SCN9A基因存在c.2841+5G>A杂合变异，Sanger测序验证该位点。cDNA序列分析表明该变异导致SCN9A基因第16和17外显子之间插入了154个碱基，导致蛋白质翻译提前终止，产生截短蛋白，影响SCN9A蛋白的正常功能。根据美国医学遗传学与基因组学学会相关指南，判定为可能致病性变异(PVS1_Strong+PM2_Supporting)。 结论 SCN9A基因c.2841+5G>A变异可能是患者的遗传学病因。上述发现丰富了SCN9A基因的变异谱，同时为患者的产前诊断和胚胎植入前遗传学检测奠定了基础。 Objective To explore the genetic etiology of a patient with epilepsy and provide genetic counseling. Methods A patient who had visited the Center for Reproductive Medicine of Shandong University on November 11, 2020 was selected as the study subject, and her clinic information was collected. Candidate variant was identified through whole exome sequencing (WES), and Sanger sequencing was used for validation. Possible transcriptional changes caused by the variant was detected by reverse transcription-PCR and Sanger sequencing. Results The patient was a 35-year-old female with no fever at the onset, loss of consciousness and abnormal firing in the temporal lobe, manifesting predominantly as convulsions and fainting. WES revealed that she had harbored a heterozygous c. 2841+ 5G>A variant of theSCN9A gene, which was verified by Sanger sequencing. cDNA sequencing confirmed that 154 bases were inserted between exons 16 and 17 of the SCN9A gene, which probably produced a truncated protein and affected the normal function of the SCN9A protein. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 2841+ 5G>A variant was classified as likely pathogenic (PVS1_Strong+ PM2_Supporting). Conclusion The c. 2841+ 5G>A variant of the SCN9A gene probably underlay the epilepsy in this patient. Above finding has enriched the variant spectrum of theSCN9A gene and provided a basis for the prenatal diagnosis and preimplantation genetic testing for this patient.

    癫痫SCN9A基因剪接位点变异成年女性

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    PSMD12基因变异所致STISS综合征患儿1例的临床特征及遗传学分析

    徐磊王依柔张倩文陈瑶...
    349-353页
    查看更多>>摘要：目的 探讨1例PSMD12基因变异所致的STISS综合征患儿的临床表型和遗传学特点。 方法 对2020年10月4日在上海交通大学医学院附属上海儿童医学中心就诊诊断的1例STISS患儿的临床资料及基因检测结果进行分析，并对STISS综合征进行文献回顾。 结果 患者PSMD12基因存在杂合无义变异c.601C>T(p.Arg201*)，国内既往未见报道，且患者身高与文献报道差异较大。 结论 患儿严重身材矮小是否为国内PSMD12基因变异的临床特征还有待进一步的探究，生长激素治疗对其的有效性和安全性仍有待于观察。 Objective To investigate the clinical and genetic characteristics of a patient with STISS syndrome due to variant of PSMD12 gene. Methods Clinical data and result of genetic testing of a patient who was admitted to Shanghai Children′s Medical Center, Shanghai Jiaotong University School of Medicine on October 4, 2020 were analyzed, together with a review of relevant literature. Results The patient was found to harbor a heterozygous c. 601C>T (p.Arg201*) nonsense variant of thePSMD12 gene, which was unreported previously. Clinically, the height of the patient has differed significantly from reported in the literature. Conclusion An extremely rare case of STISS syndrome due to variant of the PSMD12 gene has been diagnosed. Whether the severely short stature is part of the clinical spectrum for PSMD12 gene variants needs to be further explored, and the efficacy and safety of growth hormone therapy has yet to be determined.

    PSMD12基因STISS综合征基因变异

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    DLG4基因变异导致中度智力低下孕妇1例的遗传学分析

    时盼来赵学潮刘莉娜夏艳洁...
    354-359页
    查看更多>>摘要：目的 探讨1例中度智力低下(ID)孕妇的遗传学病因，并为其提供产前诊断。 方法 以2021年4月28日在郑州大学第一附属医院就诊的1例孕18周的ID孕妇作为研究对象，收集孕妇及其胎儿的临床资料，并采集其外周血样以及羊水样本用于检测。通过低深度全基因组测序(CNV-seq)分析孕妇基因组的拷贝数变异(CNVs)，再通过全外显子组测序(WES)及Sanger测序检测和验证候选基因变异。根据基因检测的结果，对胎儿进行Sanger测序验证，并通过CNV-seq及多重连接探针扩增技术(MLPA)检测胎儿的CNVs。 结果 孕妇为23岁，中度智力低下、走路偏向一侧，持物不稳，孕18+3周胎儿发育未见异常。CNV-seq未发现其存在致病CNVs，WES发现其DLG4基因存在c.1675C>T(p.Arg559*)杂合变异，经Sanger测序验证。根据美国医学遗传学与基因组学学会相关指南，上述变异被判定为可能致病性变异(PVS1+PM2_Supporting)。Sanger测序发现胎儿亦携带DLG4基因c.1675C>T(p.Arg559*)杂合变异，同时CNV-seq发现其Xp21.1区存在0.1 Mb杂合缺失，涉及DMD基因，经MLPA检测得到验证。 结论 DLG4基因c.1675C>T杂合变异可能是该孕妇智力低下的遗传学病因，其胎儿携带相同变异以及DMD基因的缺失，发生智力低下62型的风险较高。 Objective To carry out genetic testing and prenatal diagnosis for a woman featuring moderate intellectual disability (ID). Methods The patient had presented at the First Affiliated Hospital of Zhengzhou University on April 28, 2021. With informed consent, peripheral blood and amniotic fluid samples were collected for the extraction of genomic DNA. Pathogenic copy number variation (CNVs) were detected with CNV-seq, and single gene variants were detected by whole exome sequencing (WES) and Sanger sequencing. Candidate varianttions verified by Sanger sequencing, and CNV-seq and multiplex ligation-dependent probe amplification (MLPA) were used to detect fetal CNVs. Results The 23-year-old woman had moderate ID, sideway walking, and unstable holding. Ultrasonography at 18+ 3 weeks′ gestation had revealed no fetal abnormality. No pathogenic CNV was detected in the woman by CNV-seq, while WES revealed that she has harbored a heterozygous c. 1675C>T (p.Arg559*) variant of theDLG4 gene, which was verified by Sanger sequencing. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PVS1+ PM2_Supporting). Sanger sequencing has confirmed that the fetus has inherited this variant, and CNV-seq also revealed that that fetus has harbored a 0.1 Mb heterozygous deletion at Xp21.1, which has encompassed the DMD gene, and the result was verified by MLPA. Conclusion The heterozygous c. 1675C>T variant of theDLG4 gene probably underlay the mental retardation in this woman, and her fetus was found to harbor the same variant in addition with deletion of the DMD gene, which may predispose to ID type 62.

    智力障碍DLG4基因DMD基因产前诊断孕妇胎儿

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    产前诊断dup(9) 1例

    任依琳鲁宁江淼孔祥东...
    359页
    查看更多>>摘要：27岁，2020年9月因"超声提示胎儿鼻骨缺失、双侧侧脑室增宽"来郑州大学第一附属医院进行咨询。在超声引导下于孕23 +5周接受羊水穿刺。羊水细胞染色体核型为46，XN，dup(9)(p13.1p24.3)(图1)。拷贝数变异(copy number variations，CNVs)检测提示胎儿为seq[hg19]9p24.3p13.1(200 000-38 780 000)×3，提示存在约38.58 Mb的重复(图2)。本研究通过了郑州大学第一附属医院伦理委员会的审查(KS-2018-KY-36)，患者签署了临床研究知情同意书。
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    EP300基因变异致Rubinstein-Taybi综合征1例

    杨冰玉陈婷鞠翠钰李岭...
    360-363页
    查看更多>>摘要：目的 探讨1例Rubinstein-Taybi综合征(RSTS)患儿的临床特征与遗传学病因。 方法 选取2021年10月3日于苏州大学附属儿童医院内分泌遗传代谢科就诊的1例RSTS患儿为研究对象。收集患儿的临床资料，采集患儿及其父母的外周静脉血样，对患儿进行全外显子组测序(WES)，用Sanger测序对候选变异进行家系验证，并对其进行致病性分析。 结果 患儿为9岁4个月男性，主要表现为特殊面容、小头畸形、大脚趾宽大、生长发育迟缓以及智力缺陷。WES检测结果显示患儿EP300基因第20外显子存在c.3604G>T(p.E1202*)杂合变异，Sanger测序结果显示，患儿父母该位点为正常基因型，提示为新发变异。EP300基因c.3604G>T(p.E1202*)变异在神州基因组数据云、ExAC、1000 Genomes及gnomAD等数据库中均未见收录；经SIFT、PolyPhen-2及CADD等在线软件对该变异有害性分析结果显示，该变异均被预测为有害性变异。根据美国医学遗传学与基因组学学会变异相关指南，对该变异评级为致病性变异(PVS1+PS2+PM2_Supporting)。 结论 EP300基因c.3604G>T杂合变异可能是RSTS患儿的遗传学病因，患儿被诊断为RSTS 2型。上述发现进一步丰富了EP300基因的变异谱。 Objective To explore the clinical characteristics and genetic etiology of a child with Rubinstein-Taybi syndrome (RSTS). Methods A child who was admitted to the Children′s Hospital of Soochow University on October 3, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected. The child was subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing of his family members and bioinformatic analysis. Results The patient, a 9-year-and-4-month-old boy, had manifested unique facies, microcephaly, broad toes, growth retardation, and intellectual impairment. WES revealed that he has harbored a heterozygous c. 3604G>T (p.E1202*) variant in exon 20 of theEP300 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant was not found in the Shenzhou Genome data Cloud, ExAC, 1000 Genomes and gnomAD databases. Analysis with SIFT, PolyPhen-2 and CADD online software has predicted the variant to be harmful. Based on the guidelines formulated by the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion The heterozygous c. 3604G>T variant of theEP300 gene probably underlay the RSTS type 2 in this child. Above finding has expanded the variation spectrum of the EP300 gene.

    Rubinstein-Taybi综合征EP300基因新发变异发育迟缓

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