2.Progress of MECP2 duplication syndrome.
Chinese Journal of Pediatrics 2015;53(10):792-795
3.Clinical characterization and genetic testing for a patient with creatine deficiency syndrome 1.
Shu XYU ; Chen XU ; Yuan LYU ; Chuang LI ; Caixia LIU
Chinese Journal of Medical Genetics 2022;39(2):213-215
OBJECTIVE:
To explore the genetic basis for a child affected with cerebral creatine deficiency syndrome 1 (CCDS1).
METHODS:
High-throughput sequencing was carried out to screen pathogenic variant associated with the clinical phenotype of the proband. The candidate variant was verified by Sanger sequencing.
RESULTS:
High-throughput sequencing revealed that the proband has carried heterozygous c.327delG variant of the SLC6A8 gene, which was verified by Sanger sequencing.Neither parent was found to carry the same variant.
CONCLUSION
The de novo heterozygous c.327delG variant of the SLC6A8 gene probably underlay the CCDS1 in this child.
Brain Diseases, Metabolic, Inborn/genetics*
;
Creatine
;
Genetic Testing
;
Heterozygote
;
Humans
;
Mental Retardation, X-Linked
;
Mutation
4.Clinical and genetic analysis of a child with mental retardation and microcephaly with pontine and cerebellar hypoplasia.
Ziwei WANG ; Chuang LI ; Yan ZHAO ; Ling LI ; Yuan LYU ; Hong CUI
Chinese Journal of Medical Genetics 2021;38(10):985-988
OBJECTIVE:
To analyze the clinical phenotype and pathogenic variant in a child diagnosed with mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH).
METHODS:
Clinical phenotype of the child was reviewed. Whole exome sequencing was carried out for the child. Candidate variant was verified by Sanger sequencing of the family member.
RESULTS:
The proband manifested dyskinesia, development delay, cerebellar hypoplasia and bilateral hearing impairment. WES results revealed that the proband has carried a pathogenic c.1641_1644delACAA (p.Thr548Trpfs*69) variant of the CASK gene, which was verified by Sanger sequencing to be a de novo variant.
CONCLUSION
The c.1641_1644delACAA (p.Thr548Trpfs*69) variant of the CASK gene probably underlay the MICPCH in the proband. Above finding has provided a basis for genetic counseling. WES should be considered for the diagnosis of neurological dysplasia.
Cerebellum/abnormalities*
;
Child
;
Developmental Disabilities
;
Family
;
Humans
;
Mental Retardation, X-Linked
;
Microcephaly/genetics*
;
Nervous System Malformations
6.Molecular diagnosis and functional study of a pedigree affected with Lubs X-linked mental retardation syndrome.
Chen JIANG ; Nan PAN ; Weigang LYU ; Ying PENG ; Jing LIU ; Ruolan GUO ; Jiazhen CHANG ; Desheng LIANG ; Lingqian WU
Chinese Journal of Medical Genetics 2019;36(4):340-343
OBJECTIVE:
To explore the genetic basis for a pedigree affected with X-linked mental retardation.
METHODS:
The proband was subjected to chromosomal karyotyping, FMR1 mutation testing and copy number variation analysis with a single nucleotide polymorphism microarray (SNP array). His family members were subjected to multiplex ligation-dependent probe amplification (MLPA) assaying. Expression of genes within the repeated region were analyzed.
RESULTS:
The proband had a normal chromosomal karyotype and normal number of CGG repeats within the FMR1 gene. SNP array identified a 370 kb duplication in Xq28 (ChrX: 153 027 633-153 398 515), which encompassed 14 genes including MECP2. The patient was diagnosed as Lubs X-linked mental retardation syndrome (MRXSL). MLPA confirmed the presence of copy number variation, its co-segregation with the disease, in addition with the carrier status of females. Genes from the duplicated region showed higher levels of expression (1.79 to 5.38 folds) within peripheral blood nucleated cells of the proband.
CONCLUSION
The patients were diagnosed with MRXSL. The expression of affected genes was up-regulated due to the duplication. Genetic counseling and prenatal diagnosis may be provided based on the results.
DNA Copy Number Variations
;
Female
;
Fragile X Mental Retardation Protein
;
Humans
;
Mental Retardation, X-Linked
;
Methyl-CpG-Binding Protein 2
;
Pedigree
;
Pregnancy
7.MECP2 duplication syndrome: a clinical analysis of three cases and literature review.
Dan-Xia TANG ; Dong-Fang LI ; Ruo-Hao WU ; Li-Na ZHANG ; Xiang-Yang LUO
Chinese Journal of Contemporary Pediatrics 2017;19(5):489-493
MECP2 duplication syndrome (MDS) is a rare pediatric disease and mainly manifests as delayed motor development, language loss or delay, recurrent infection, severe intellectual disability, epilepsy, autistic symptoms, and early infantile hypotonia. In this article, the three children with this disease were all boys. Cases 1 and 2 had delayed motor development, and language loss or delay as initial manifestations, and case 3 had recurrent infection as initial manifestation. Physical examination showed hypotonia and negative pathological signs in each case. Case 1 had tonic-clonic seizures and electroencephalography showed focal seizures, for which he was given oxcarbazepine, levetiracetam, and clonazepam as the antiepileptic treatment to control seizures. Case 3 experienced one absence seizure and three head-nodding seizures with normal electroencephalographic findings during these seizures, and therefore, he was not given antiepileptic treatment. In each case, recurrent infection was improved with the increase in age, but there were no significant improvements in language or intelligence. Array-based comparative genomic hybridization (aCGH) showed MECP2 duplication in X chromosome in each case, and so they were diagnosed with MDS. MDS should be considered for children with delayed development complicated by recurrent infection and epileptic seizures, and early aCGH helps with the diagnosis of this disease.
Child
;
Comparative Genomic Hybridization
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Humans
;
Infant
;
Male
;
Mental Retardation, X-Linked
;
complications
;
genetics
;
Methyl-CpG-Binding Protein 2
;
genetics
8.Advance in research on MECP2 corrected duplication syndrome.
Chinese Journal of Medical Genetics 2015;32(3):426-429
Methyl-CpG-binding protein 2 gene (MECP2; OMIM 300005) is located at chromosome Xq28. Mutations of the gene including point mutation, duplication and deletion can lead to severe neurodevelopmental disorders. The disease caused by duplication of the entire MECP2 gene, named as MECP2 duplication syndrome, is mostly seen in males. The clinical manifestation of this syndrome include mental retardation, hypotonia, poor speech development, recurrent infection, progressive spasticity, epilepsy, autism or autistic features with or without midface hypoplasia. Most patients have inherited the duplication from their unaffected mothers, with only a few cases having de novo mutation. Females with duplicated MECP2 gene are typically asymptomatic because of a skewed X chromosome inactivation (XCI) pattern. Proposed mechanisms of this genomic rearrangement include fork stalling and template switching (FoSTeS) and microhomology mediated break-induced replication (MMBIR). Since no effective treatment is available for this disease, proper genetic counseling and prenatal diagnosis for the high risk families are crucial.
Animals
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Female
;
Gene Duplication
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Humans
;
Male
;
Mental Retardation, X-Linked
;
genetics
;
metabolism
;
Methyl-CpG-Binding Protein 2
;
genetics
;
metabolism
9.Clinical features and gene variant of a pedigree affected with X-linked recessive mental retardation Claes-Jensen type.
Ning DING ; Pingping ZHANG ; Yingying MAO ; Shuo FENG ; Zhijie GAO ; Qian CHEN ; Xue ZHANG
Chinese Journal of Medical Genetics 2020;37(12):1352-1355
OBJECTIVE:
To explore the genetic basis for a pedigree affected with X-linked recessive mental retardation Claes-Jensen type.
METHODS:
Genomic DNA was extracted from peripheral blood samples of the patient, his parents (phenotypically normal) and two elder brothers with similar clinical manifestations. Whole exome sequencing was carried out for the proband, and the result was verified by Sanger sequencing.
RESULTS:
The proband was found to harbor a hemizygous c.1565C>T missense variant in exon 11 of the KDM5C gene. The transition has resulted in replacement of serine by phenylalanine at position 522 (p.Ser522Phe). Sanger sequencing showed that the patient's two elder brothers and mother carried the same variant, which was predicted to be probably damaging by SIFT, PolyPhen2 and Mutation_Taster. The three affected brothers presented with similar clinical phenotypes characterized by mental retardation, speech delay, behavioral problem, self-limited epilepsy responsible to medication, short stature and microcephaly. The mother only had mild cognitive impairment and learning disability. The same variant was not found in their father and was unreported previously.
CONCLUSION
The c.1565C>T (p.Ser522Phe) of the KDM5C gene probably underlay the X-linked recessive mental retardation Claes-Jensen type in this pedigree.
Aged
;
Female
;
Histone Demethylases/genetics*
;
Humans
;
Male
;
Mental Retardation, X-Linked/pathology*
;
Mutation, Missense/genetics*
;
Pedigree
;
Phenotype
;
Whole Exome Sequencing
10.Analysis of a patient with X-linked mental retardation by next generation sequencing.
Yuqiang LYU ; Yali YANG ; Yi LIU ; Zhongtao GAI
Chinese Journal of Medical Genetics 2018;35(2):257-260
OBJECTIVETo explore the clinical and genetic features of a Chinese boy featuring X-linked mental retardation.
METHODSClinical features of the patient were analyzed. The DNA of the patient and his parents was extracted and sequenced by next generation sequencing. The results were validated and analyzed with software.
RESULTSThe child displayed X-linked mental retardation. Sequencing showed the patient has carried a c.455T>C (p.L152P) mutation of the GRIA3 gene inherited from his mother.
CONCLUSIONThe c.455T>C (p.L152P) mutation of the GRIA3 gene probably underlies the X-linked mental retardation in this child.
Child, Preschool ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Male ; Mental Retardation, X-Linked ; genetics ; Mutation ; Receptors, AMPA ; genetics