中华医学遗传学杂志最新文献

{"title":"[Clinical features and genetic analysis of two children with Mowat-Wilson syndrome due to variants of ZEB2 gene].","authors":"Chunxiao Han, Lulu Yan, Yuxin Zhang, Haibo Li","doi":"10.3760/cma.j.cn511374-20240722-00402","DOIUrl":"10.3760/cma.j.cn511374-20240722-00402","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical features and genetic variants in two children with Mowat-Wilson syndrome (MWS).</p><p><strong>Methods: </strong>Two children admitted to the Affiliated Women and Children's Hospital of Ningbo University respectively in May and October 2022 were selected as the study subjects. Clinical data of the patients were collected. The two children were subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of the Women and Children's Hospital of Ningbo University (Ethic No.EC2020-014).</p><p><strong>Results: </strong>Child 1 was a 3-year-old male who had presented with epilepsy. Cranial MRI revealed hypoplasia of corpus callosum, down-slanting eyes, hypotonia, developmental delay, and recurrent constipation. The child was found to harbor a de novo c.262dup (p.Ile88Asnfs*31) missense variant of the ZEB2 gene, which was detected in neither parents. Child 2 was a 6-months-old male presented with epilepsy, with no apparent anomaly detected by cranial MRI. The child had featured developmental delay, inverted eyelash, atrial septal defect, and cryptorchidism. WES revealed that he had harbored a c.3213_3224delinsCTAC (p.Q1072Yfs*49) frameshifting variant of the ZEB2 gene, which was detected in neither parents. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were determined as likely pathogenic, with ratings of PVS1_Strong+PM2_Supporting+PM6 and PVS1_Strong+PM2_Supporting+PM6. Both variants had resulted in premature occurrence of stop codons.</p><p><strong>Conclusion: </strong>By combining their clinical features and results of genetic testing, both children had been diagnosed with MWS due to variants of the ZEB2 gene. Above findings have enriched the mutational spectrum of MWS and provided a basis for the prenatal diagnosis and genetic counseling.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 12","pages":"1448-1455"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Methylation epigenetic analysis of a pedigree affected with Fragile X syndrome based on Nanopore long-read sequencing].","authors":"Conghui Wang, Panlai Shi, Li'na Liu, Xuechao Zhao, Xiangdong Kong","doi":"10.3760/cma.j.cn511374-20230910-00123","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20230910-00123","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic basis for a Chinese pedigree affected with Fragile X syndrome (FXS) through Nanopore long-read sequencing.</p><p><strong>Methods: </strong>A FXS pedigree who had undergone genetic counseling at the First Affiliated Hospital of Zhengzhou University in April 2023 was selected as the study subject. Nanopore long-read sequencing, triplet-repeat primed PCR (TP-PCR), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and trinucleotide polymorphism genotyping of androgen receptor (AR) gene were used to analyze the FMR1 CGG repeat number, methylation, and X chromosome inactivation of the pedigree members. This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No. KS-2018-KY-36).</p><p><strong>Results: </strong>Full mutation and CpG island hypermethylation were detected in the proband. The elder sister of the proband had full mutation of the FMR1 gene on one X chromosome and hypermethylation of CpG island, while the FMR1 gene on the other X chromosome was normal. FMR1 premutation was detected in the proband's mother.</p><p><strong>Conclusion: </strong>Nanopore long-read sequencing can simultaneously detect the dynamic mutation and methylation status of the FMR1 gene on the two X chromosomes of females, which has important value for the diagnosis of FXS in different genders.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1290-1295"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Research progress on inherited distal renal tubular acidosis due to variants of V-ATPase-related genes].","authors":"Siqi Peng, Qianqian Wu, Junlan Yang, Bin Wang, Xiaoliang Zhang","doi":"10.3760/cma.j.cn511374-20240224-00120","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20240224-00120","url":null,"abstract":"<p><p>V-ATPases are a class of multi-subunit protein complexes that utilize energy derived from ATP hydrolysis for mediating H⁺ transport across cell membranes, which plays an important role in a range of life activities by acidifying the intracellular and extracellular environment. Variants of V-ATPase genes may lead to complete or partial loss of V-ATPase activity, which in turn may impair the ability of type A intercalated cells in renal tubules to pump H⁺ into the tubular lumen, ultimately resulting in the onset of autosomal recessive distal renal tubular acidosis (dRTA). With the rapid development of molecular techniques, ATP6V0A4 and ATP6V1B1 have now been identified as the pathogenic genes for dRTA. Moreover, animal and cell experiments have substantiated the implication of V-ATPase subunit genes including ATP6V1C2 and ATP6V1G3 in the development of dRTA, though clinical evidence is still limited. This article has reviewed recent progress on the genetic and molecular mechanisms of V-ATPase subunit gene variants which can lead to dRTA, which may shed light on the diagnosis and treatment of this disease.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1399-1404"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Genetic analysis of a child with Malan syndrome].","authors":"Baosong Wang, Xuexi Zhang, Yunjia Li, Tao Liu, Lin Li, Qin Meng","doi":"10.3760/cma.j.cn511374-20240621-00347","DOIUrl":"10.3760/cma.j.cn511374-20240621-00347","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic basis of a child with mental retardation and developmental delay.</p><p><strong>Methods: </strong>A child who had attended the genetic clinic of Linyi People's Hospital from October 2023 to April 2024 was selected as the study subject. Intelligence and development were assessed with simplified Peabody scale. Electroencephalogram and imaging data were collected. Peripheral blood samples of the child and her parents were collected for the screening of genetic metabolic diseases, chromosomal karyotyping, and trio-whole genome sequencing (trio-WGS) analysis. Candidate variant was verified by Sanger sequencing, and RNAseq was carried out to verify the alternative splicing due to the candidate variant. This study has been approved by the Medical Ethics Committee of Linyi People's Hospital (No. YX200083).</p><p><strong>Results: </strong>The patient was an 8-year-and-11-month-old girl. Both of her parents had normal phenotypes. The child was assessed by the simplified Peabody scale as having intellectual disability and developmental delay. MRI showed no definite abnormal signals within the brain parenchyma, and electroencephalogram was normal. Screening of genetic metabolic diseases showed no obvious abnormality. Chromosomal karyotype was normal. Trio-WGS has detected a c.697+1G>A variant in the intron 4 of the NFIX gene, along with 9 other variants within eight genes. The c.697+1G>A variant may cause abnormal splicing of the NFIX gene transcript. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.697+1G>A variant was predicted to be pathogenic (PVS1+PS2+PM2_Supporting), while the evidence for pathogenicity of the other 9 variants was insufficient.</p><p><strong>Conclusion: </strong>The novel de novo c.697+1G>A variant of the NFIX gene probably underlay the pathogenesis of the child, which may have caused the disease by leading to abnormal splicing.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1330-1334"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Analysis of non-targeted variants by invasive prenatal diagnosis for pregnant women undergoing preimplantation genetic testing].","authors":"Si Li, Ziyi Xiao, Chenyu Gou, Xiaolan Li, Yijuan Huang, Yuanqiu Chen, Shujing He, Zhiqiang Zhang, Zi Ren, Song Guo, Weiying Jiang, Yu Gao","doi":"110.3760/cma.j.cn511374-20240320-00181","DOIUrl":"https://doi.org/110.3760/cma.j.cn511374-20240320-00181","url":null,"abstract":"<p><strong>Objective: </strong>To compare the results of invasive prenatal diagnosis and preimplantation genetic testing (PGT) and explore the underlying mechanism.</p><p><strong>Methods: </strong>Clinical data of pregnant women undergoing PGT and invasive prenatal diagnosis at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022 were collected. The results of PGT and invasive prenatal diagnosis were compared, and the outcomes of pregnancies were followed up. This study has been approved by the Medical Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (No. 2022ZSLYEC-491).</p><p><strong>Results: </strong>A total of 172 couples were included in this study, and 26 non-targeted variants were discovered upon prenatal diagnosis, including 10 cases (38.5%) by chromosomal karyotyping, 15 (57.7%) by chromosomal microarray analysis (CMA), and 1 (3.8%) by whole exome sequencing. The 10 karyotypic anomalies had included 6 chromosomal polymorphisms, 2 chromosomal mosaicisms, 1 paternally derived translocation, and 1 missed maternal chromosomal inversion. CMA has identified 15 copy number variations (CNVs), which included 11 microdeletions and microduplications, 3 loss of heterozygosity, and 1 low-level mosaicism of paternal uniparental disomy. One CNV was classified as pathogenic, and another one was likely pathogenic, whilst the remaining 13 were classified as variants of uncertain significance. Therefore, 8.7% of CNVs was detected by invasive prenatal diagnosis after PGT. 92.3% (24/26) of the non-targeted variants have been due to technological limitations of next-generation sequencing (NGS).</p><p><strong>Conclusion: </strong>Invasive prenatal diagnosis after PGT can detect non-targeted variants, which may further reduce the incidence of birth defects.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1283-1289"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Prenatal diagnosis of a fetus with mosaicism ring chromosome 2].","authors":"Ying Zhou, Lingling Xu, Lulu Yan, Changshui Chen, Haibo Li","doi":"10.3760/cma.j.cn511374-20240313-00172","DOIUrl":"10.3760/cma.j.cn511374-20240313-00172","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic basis for a fetus with increased risk for Down syndrome and cardiac anomalies discovered by prenatal ultrasonography.</p><p><strong>Methods: </strong>A pregnant woman presented at the Women and Children's Hospital of Ningbo University on August 21, 2023 were selected as the study subject. Clinical data were retrospectively analyzed. Maternal peripheral blood sample was collected for non-invasive prenatal testing (NIPT) based on fetal free DNA. Amniotic fluid sample was collected for G-banded chromosomal karyotyping analysis. Trio-whole exome sequencing (WES) was also carried out on the amniotic fluid sample and peripheral blood samples from the couple. Copy number variation (CNV) identified by the WES was validated by real-time fluorescent quantitative PCR (qPCR). Chromosomal karyotyping was also carried out for the couple. This study has been approved by the Medical Ethics Committee of Women and Children's Hospital of Ningbo University (No. EC2020-048).</p><p><strong>Results: </strong>Ultrasound examination at 22⁺⁶ gestational weeks had indicated intrauterine growth retardation (IUGR). The fetus was also found to have ventricular septal defect, overriding aorta and pulmonary stenosis. NIPT indicated a low risk for aneuploidy of chromosomes 13, 18 and 21. G-banding analysis revealed that the fetus had a karyotype of 45,XY,-2[5]/46,XY,r(2)(p25q37)[55]. WES has identified a deletion of approximately 1 614.28 kb in the 2p25.3 region, namely seq[hg38]del(2)(p25.3p25.3)chr2: g.10500_1624775del. The same deletion was found in neither parent, suggesting a de novo origin. qPCR results confirmed the expression of target genes in the fetal sample to be significantly reduced, whilst no similar anomaly was found in either parent.</p><p><strong>Conclusion: </strong>The mosaicism ring chromosome 2 probably underlay the IUGR and cardiovascular malformations in this fetus.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1356-1362"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Clinical and genetic analysis of a patient with Ataxia and vitamin E deficiency due to homozygous variant of TTPA gene].","authors":"Mei Wang, Cheng Xiang, Zhidan Hong, Ling Ma, Ming Zhang, Yuanzhen Zhang","doi":"10.3760/cma.j.cn511374-20240103-00006","DOIUrl":"10.3760/cma.j.cn511374-20240103-00006","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical phenotype and genetic characteristics of a patient with Ataxia and vitamin E deficiency syndrome (AVED) due to a variant of TTPA gene.</p><p><strong>Methods: </strong>A patient diagnosed with AVED (proband), intended for assisted reproductive technology for pregnancy in Zhongnan Hospital of Wuhan University in July 2023, was selected as research subject. Clinical data of the proband were collected, and 2 mL of peripheral venous blood samples were collected from the proband and her father and siblings for serum vitamin E level testing. Whole exome sequencing (WES) was carried out. Pathogenic variants were selected based on American public archive of interpretations of clinically relevant variants (ClinVar). Sanger sequencing was performed to validate the candidate variants detected by WES. Pathogenicity of variants was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and the impact of variants was analyzed using multiple bioinformatics tools including SIFT, Mutation Taster, CADD, and SpliceAI. Information on the protein domains was obtained from ClinVar and dbSNP databases, and a hotspot map for the variants of protein-coding region was constructed. This study was approved by the Medical Ethics Committee of Zhongnan Hospital of Wuhan University (No. 2023068K).</p><p><strong>Results: </strong>The proband has a significantly low serum level of vitamin E (5.186 μg/mL), while her father and siblings were normal. WES revealed that she has harbored a homozygous missense c.2T>A (p.0?) variant of the TTPA gene, for which her father and younger sister were heterozygous carriers. Based on the guidelines from the ACMG, the missense c.2T>A (p.0?) variant of the TTPA gene was classified as pathogenic (PVS1+PM2+PM3). Multiple bioinformatics tools had predicted this variant to be located in the initiation codon region and may lead to abnormal synthesis of the TTPA protein, indicating it was deleterious. The hotspot map based on ClinVar and dbSNP databases showed an even distribution of variants across 5 structural domains of the TTPA protein, with high conservation of the first amino acid residue across various species.</p><p><strong>Conclusion: </strong>The homozygous c.2T>A (p.0?) variant of the TTPA gene probably underlie the AVED in the proband. Above discovery has enriched the mutational spectrum of AVED and provided a basis for the diagnosis, genetic counseling, and assisted reproductive strategies for this family.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1335-1343"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Genetic analysis of a child with Congenital insensitivity to pain due to compound heterozygous variants of SCN9A gene].","authors":"Xiaolan Tan, Yuan Yang, Yunqiang Liu","doi":"10.3760/cma.j.cn511374-20240119-00055","DOIUrl":"10.3760/cma.j.cn511374-20240119-00055","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic etiology of a child featuring multiple fractures and congenital insensitivity to pain (CIP).</p><p><strong>Methods: </strong>A child who had presented at the West China Hospital of Sichuan University on March 16, 2023 for recurrent fractures and CIP was selected as the study subject. Peripheral blood samples of the child and his parents was collected. Trio-whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of West China Hospital of Sichuan University (No. 2019-772).</p><p><strong>Results: </strong>Trio-whole exome sequencing revealed that the child has harbored compound heterozygous variants of the SCN9A gene, namely c.560delC (p.P187Rfs*15) and c.829C>T (p.R277*), which were respectively inherited from his father and mother. Homozygous c.829C>T variant had been demonstrated as pathogenic among CIP patients, whilst the c.560delC (p.P187Rfs*15) variant was unreported previously and predicted to be pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (ACMG).</p><p><strong>Conclusion: </strong>The child was diagnosed with CIP due to the compound heterozygous variants of the SCN9A gene. Above finding has enabled genetic counselling and reproductive guidance for this family.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1344-1348"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Anomalies of ATP-dependent chromatin remodeling complexes and human neurodevelopmental genetic disorders].","authors":"Yun Gui, Lulu Li, Jian Wang","doi":"10.3760/cma.j.cn511374-20240226-00123","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20240226-00123","url":null,"abstract":"<p><p>ATP-dependent chromatin remodeling complexes play crucial roles in various biological processes including enhancing local DNA accessibility, regulating gene transcription, and facilitating DNA replication and repair. Based on their functional structural domains, these complexes may be categorized into four families, including SWI/SNF, ISWI, CHD and INO80. Such families are vital factors for regulating gene expression and play pivotal roles in developmental processes. Variants of genes encoding the components of such complexes have been closely associated with human developmental disorders and neurodevelopmental genetic syndromes. This review has summarized the classification, fundamental functions and underlying mechanism of the ATP-dependent chromatin remodeling complexes, as well as common neurological genetic disorders due to variants of genes encoding the subunits of such complexes.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1387-1392"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Analysis of clinical characteristics and genetic variants in two pedigrees affected with Autosomal dominant intellectual developmental disorder 49].","authors":"Yuqiang Lyu, Yanqing Zhang, Ning Li, Kaihui Zhang, Min Gao, Jian Ma, Weitong Guo, Yi Liu, Zhongtao Gai","doi":"10.3760/cma.j.cn-511374-20240102-00002","DOIUrl":"https://doi.org/10.3760/cma.j.cn-511374-20240102-00002","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).</p><p><strong>Methods: </strong>Two MRD49 pedigrees which were admitted to the Children's Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Shandong University (Ethics No. SDFE-IRB/T-2022002).</p><p><strong>Results: </strong>Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PM2_Supporting+PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PS2+PM2_Supporting).</p><p><strong>Conclusion: </strong>This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1296-1301"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}