1.Clinical features and genetic analysis of a case of Wiedemann-Steiner syndrome due to variant of KMT2A gene.
Chinese Journal of Medical Genetics 2023;40(2):222-225
OBJECTIVE:
To explore the clinical features and genetic etiology of a child with Wiedemann-Steiner syndrome.
METHODS:
A child with WSS who was admitted to the Hematology Department of Tianjin Children's Hospital in May 2021 was selected as the subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. The child was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing of the child and his parents.
RESULTS:
The main clinical features of the child have included pancytopenia, growth and mental retardation, and facial dysmorphism. Whole exome sequencing revealed that the child has harbored a heterozygous variant of the KMT2A gene, namely c.7804delA (p.M2602Cfs*39). Sanger sequencing verified the variant to be de novo in origin. The variant was unreported previously and predicted to be pathogenic based on the guidelines of American College of Medical Genetics and Genomics (PVS1+PS2+PM2).
CONCLUSION
The heterozygous c.7804delA (p.M2602Cfs*39) variant of the KMT2A gene probably underlay the WSS in this child. Above finding has enriched the mutational spectrum and clinical phenotypes of the KMT2A gene.
Humans
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Abnormalities, Multiple/genetics*
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Intellectual Disability/genetics*
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Mutation
;
Syndrome
2.Clinical and genetic analysis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome due to a novel frameshift variant of DYM gene.
Lele KUANG ; Rui PENG ; Bin LIU ; Di XI ; Qiurong CHANG ; Yuping GAO
Chinese Journal of Medical Genetics 2022;39(4):370-373
OBJECTIVE:
To explore the genetic basis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome.
METHODS:
Whole exome sequencing and Sanger sequencing were carried out to detect potential pathogenic variants associated with the syndrome. The function of candidate variant was verified by Western blotting.
RESULTS:
A novel homozygous variant, c.1222delG of the DYM gene was detected in the two affected siblings, for which both parents were heterozygous carriers. The variant has caused replacement of Asp by Met at amino acid 408 and generate a premature stop codon p.Asp408Metfs*10. Western blotting confirmed that the variant can result in degradation of the mutant DYM protein, suggesting that it is a loss of function variant.
CONCLUSION
The homozygous c.1222delG frameshift variant of the DYM probably underlay the Dyggve-Melchior-Clausen syndrome in the two affected siblings. Above findings has enabled clinical diagnosis and genetic counseling for the family.
China
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Dwarfism/genetics*
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Humans
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Intellectual Disability
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Osteochondrodysplasias/genetics*
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Pedigree
3.Clinical and genetic analysis of a child with mental retardation autosomal dominant 7.
Zhihong ZHUO ; Yao WANG ; Tianjiao FU ; Xiao FANG ; Xiaoli XU ; Yue WANG ; Huimin KONG ; Huaili WANG
Chinese Journal of Medical Genetics 2022;39(5):530-533
OBJECTIVE:
To analyze the clinical and genetic characteristics of a child with clinical manifestations of hypoplasia, epilepsy and abnormal face.
METHODS:
The clinical data of the child were collected. The peripheral blood samples of the patient and his parents were extracted for high-throughput sequencing, and Sanger sequencing verification and bioinformatics analysis were performed to detect suspected pathogenic variants.
RESULTS:
The clinical manifestations of the child were overall developmental backwardness, seizures, autism, and special facial appearance. High throughput sequencing showed that there was a heterozygous mutation of exon 11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) of the DYRK1A gene. The same variant was found in neither of her parents, suggesting that it has a denovo origin.
CONCLUSION
The exon11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) mutation in DYRK1A gene was the genetic etiology of the case, which enriches the pathogenic gene spectrum of DYRK1A and provides the basis for clinical diagnosis and genetic counseling.
Arthrogryposis
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Child
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Facies
;
Female
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Heterozygote
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Humans
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Intellectual Disability/genetics*
;
Mutation
4.Mental retardation, hypogonadism, epilepsy, white matter lesions and hyperhomocysteinemia in a family.
Dandan SHANG ; Changhe SHI ; Jie QIN ; Bo SONG ; Yuming XU ; Shilei SUN
Chinese Journal of Medical Genetics 2015;32(1):136-137
Adult
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Epilepsy
;
genetics
;
Humans
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Hyperhomocysteinemia
;
genetics
;
Hypogonadism
;
genetics
;
Intellectual Disability
;
genetics
;
Male
;
White Matter
;
pathology
6.De novo variant of CSNK2B causes Poirier-Bienvenu neurodevelopmental syndrome: two case report.
Jia ZHANG ; Yang LI ; Huan LUO ; YaJun SHEN ; Meng YUAN ; Zuozhen YANG ; Jing GAN
Chinese Journal of Medical Genetics 2022;39(5):484-487
OBJECTIVE:
To analyze the clinical characteristics and CSNK2B gene variant of 2 children with Poirier-Bienvenu neurodevelopmental syndrome, and to identify the possible pathogenic causes and provide evidence for clinical diagnosis.
METHODS:
Two children with Poirier-Bienvenu neurodevelopmental syndrome were selected from West China Second University Hospital, Sichuan University. The clinical manifestations, laboratory examination and CSNK2B gene variant were analyzed.
RESULTS:
The main manifestations of 2 children were epilepsy, motor or intellectual retardation. Whole exon sequencing showed that CSNK2B gene c. 291+4A>T heterozygous splicing variant was found in case one, and CSNK2B copy number variation(CNV) was lost in case two. Case one received no special treatment, followed up for 8+ months, seizures and motor development were improved; case two had recurrent seizures for 9+ years, and received levetiracetam and clonazepam antiepileptic treatment. No seizures have occurred for 2 years now, and a large number of epileptic discharges can still be seen in video electroencephalogram (VEEG) with slightly backward intelligence and language development.
CONCLUSION
Our study further proves that the pathogenic variant of CSNK2B is related to epilepsy with developmental disorder, and enrich is the CSNK2B gene variant spectrum. The pathogenesis of CSNK2B has great clinical heterogeneity, with great difference in severity of nervous system injury and different prognosis, and agenesis of corpus callosum may be one of its clinical phenotypes.
Child
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DNA Copy Number Variations
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Developmental Disabilities/genetics*
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Epilepsy/genetics*
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Humans
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Intellectual Disability/genetics*
;
Seizures/genetics*
7.RABL2B gene mutation in a girl with mental retardation and hyperactivity.
Li-Na ZHU ; Xin LIU ; Chun-Zhi WANG ; Yan WANG ; Xiao YANG ; Wei PENG ; Wei WANG ; Ning MA
Chinese Journal of Contemporary Pediatrics 2009;11(9):780-781
Child
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Female
;
Humans
;
Hyperkinesis
;
genetics
;
Intellectual Disability
;
genetics
;
Mutation
;
rab GTP-Binding Proteins
;
genetics
8.Genetic analysis of a case with Pitt-Hopkins syndrome due to variant of TCF4 gene.
Jian MA ; Huawei ZHANG ; Kaihui ZHANG ; Yuqiang LYU ; Min GAO ; Dong WANG ; Zhongtao GAI ; Yi LIU
Chinese Journal of Medical Genetics 2020;37(11):1253-1256
OBJECTIVE:
To explore the genetic basis of a patient presenting with dysmorphism, intellectual disability, psychomotor delay and hypoplasia of corpus callosum by using next generation sequencing.
METHODS:
Genomic DNA was extracted from peripheral blood samples of the patient and his family members and subjected to exome sequencing. Suspected variants were verified with Sanger sequencing.
RESULTS:
The patient was found to carry a heterozygous c.1357delAinsGGA variant in exon 11 of the TCF4 gene, which was verified as de novo by Sanger sequencing. The variant may result in a truncated protein and affect its function.
CONCLUSION
The heterozygous c.1357delAinsGGA variant the TCF4 gene probably underlies the disease in the proband.
Facies
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Genetic Testing
;
Humans
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Hyperventilation/genetics*
;
Intellectual Disability/genetics*
;
Male
;
Transcription Factor 4/genetics*
9.Clinical and genetic analysis of a patient with Mowat-Wilson syndrome.
Pingli ZHANG ; Yanqi HOU ; Peiyuan LIAO ; Xiang YUAN ; Na LI ; Qikun HUANG ; Jing YANG
Chinese Journal of Medical Genetics 2021;38(5):465-468
OBJECTIVE:
To summarize the clinical phenotype and genotype of a Chinese child affected with Mowat-Wilson syndrome (MWS).
METHODS:
Clinical data of the patient were collected. The patient was analyzed by whole-exome sequencing (WES) as well as Sanger sequencing.
RESULTS:
The patient was a male infant with recurrent fever and slow growth. He also had characteristic facies, recurrent spasm, and growth retardation. WES revealed that he has carried a heterozygous nonsense c.2609C>G (p.Ser870X) variant of the ZEB2 gene (30% mosaicism). Based on the American College of Medical Genetics and Genomics standards and guidelines, the variant was predicted to be pathogenic (PVS1+PS1+PS2+PM2).
CONCLUSION
The c.2609C>G variant of the ZEB2 gene probably underlay the MWS in this child. The mosaicism of the variant may explain his mild symptoms.
Child
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Facies
;
Hirschsprung Disease/genetics*
;
Humans
;
Infant
;
Intellectual Disability/genetics*
;
Male
;
Microcephaly/genetics*
;
Mutation
10.Clinical phenotype and genetic analysis of twelve children with ring chromosomes.
Hongsheng YU ; Xijiang HU ; Pingxia XIANG ; Ling LIU ; Chi ZHANG ; Hui HUANG ; Lifang NING
Chinese Journal of Medical Genetics 2023;40(2):191-194
OBJECTIVE:
To explore the prevalence and clinical manifestations of ring chromosomes among children featuring abnormal development.
METHODS:
From January 2015 to August 2021, 7574 children referred for abnormal development were selected, and their peripheral blood samples were subjected to G-banded chromosomal karyotyping analysis.
RESULTS:
Twelve cases of ring chromosomes were detected, which have yielded a prevalence of 0.16% and included 1 r(6), 2 r(9), 1 r(13), 1 r(14), 2 r(15), 1 r(21) and 3 r(X). The children had various clinical manifestations including growth and mental retardation, limb malformation, and congenital heart disease. For two children with r(9) and two with r(15) with similar breakpoints, one child with r(9) and one with r(15) only had growth retardation, whilst another with r(9) and another with r(15) also had peculiar facies and complex congenital heart disease. The r(X) has featured some manifestations of Turner syndrome.
CONCLUSION
Ring chromosomes are among the common causes for severe growth and mental retardation in children with diverse clinical phenotypes. Clinicians should pay attention to those with developmental anomalies and use chromosomal analysis to elucidate their genetic etiology.
Humans
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Ring Chromosomes
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Intellectual Disability/genetics*
;
Turner Syndrome/genetics*
;
Phenotype
;
Heart Defects, Congenital/genetics*