Humans ; Mental Retardation, X-Linked/genetics* ; Methyl-CpG-Binding Protein 2/genetics* ; Gene Duplication

Fragile X mental retardation 1 is the gene underlying fragile X syndrome (FXS). Its product, fragile X mental retardation protein, is closely involved with development of brain and neurons. PCR and Southern blotting have been the major methods for laboratory diagnosis of FXS. In this article, the progress in the molecular diagnosis of FXS is reviewed.
Fragile X Mental Retardation Protein ; genetics ; Fragile X Syndrome ; diagnosis ; genetics ; Humans ; Pathology, Molecular ; methods

Humans ; Mental Retardation, X-Linked ; genetics ; Methyl-CpG-Binding Protein 2 ; genetics

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

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

OBJECTIVE: To explore the genetic basis for a family affected with mental retardation combined with autism. METHODS: For the family featuring X-linked recessive inheritance of mental retardation combined with autism, clinical data and peripheral blood samples were collected. Potential mutations of genes associated with intellectual impairment were sequenced with an Ion PGM platform. Suspected mutations were verified with a PCR-Sanger sequencing method. RESULTS: The patient with mental retardation had mild abnormal electroencephalograph(EEG), while brain MRI and CT scans showed no obvious abnormality. Two ABC (autism behavior checklist) testing scores were 73 and 66 when he was 7- and 13-year-old, respectively. A novel hemizygous mutation, c.64C>T (p.L22F), was detected in the GRIA3 gene in the patient, for which his mother was a heterozygous carrier. The mutation site was predicted to be possibly damaging and disease causing by PolyPhen_2 and MutationTaster. CONCLUSION The novel hemizygous c.64C>T (p.L22F) mutation of the GRIA3 gene probably underlies the phenotypes of mental retardation combined with autism in this family. Considering the variable clinical manifestation of mental retardation and genetic heterogeneity of autism, genetic testing is essential for making the correct diagnosis.
Adolescent ; Autistic Disorder ; genetics ; Child ; Humans ; Intellectual Disability ; genetics ; Male ; Mental Retardation, X-Linked ; genetics ; Mutation ; Receptors, AMPA ; genetics

Fragile X-associated tremor/ataxia syndrome(FXTAS) is a neurodegenerative disease caused by FMR1 gene permutation(PM). The main clinical manifestations are intention tremor and/or ataxia, and the pathogenesis was related to RNA toxicity. In this paper, the research progress of clinical manifestatios, pathological characteristics, epidemiology and molecular mechanisms will be reviewed.
Ataxia ; genetics ; Female ; Fragile X Mental Retardation Protein ; genetics ; Fragile X Syndrome ; complications ; diagnosis ; genetics ; pathology ; Humans ; Male ; Tremor ; genetics

OBJECTIVE: To analyze the (CGG)n repeats of FMR1 gene among patients with unexplained mental retardation. METHODS: For 201 patients with unexplained mental retardation, the (CGG)n repeats of the FMR1 gene were analyzed by PCR and FragilEase RESULTS: For the 201 patients with unexplained mental retardation, 15 were identified with full mutations of the FMR1 gene. The prevalence of fragile X syndrome (FXS) in patients with unexplained mental retardation was determined as 7.5% (15/201). Prenatal diagnosis was provided for 6 pregnant women with pre- or full mutations. Analysis revealed that women with mental retardation and full FMR1 mutations exhibited a skewed XCI pattern with primary expression of the X chromosome carrying the mutant allele. CONCLUSION FXS has a high incidence among patients with unexplained mental retardation. Analysis of FMR1 gene (CGG)n repeats in patients with unexplained mental retardation can facilitate genetic counseling and prenatal diagnosis for their families. FMR1 gene (CGG)n repeats screening should be recommended for patients with unexplained mental retardation.
Female ; Fragile X Mental Retardation Protein/genetics* ; Fragile X Syndrome/genetics* ; Humans ; Intellectual Disability/genetics* ; Mutation ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To analyze the clinical phenotype and genetic variants of a child with X-linked mental retardation caused by IQSEC2 gene mutation, and provide reference for the diagnosis of the disease. METHODS: The child was subjected to next generation sequencing (NGS), and the diagnosis was made by taking consideration of her clinical characteristics. RESULTS: The child has presented with global developmental delay, particularly in fine motor skill and language development, in addition with intellectual disability. Genetic testing revealed that she has harbored a heterozygous c.1861dup variant of the IQSEC2 gene, which was not detected in either parent. CONCLUSION The de novo c.186ldup variant of the IQSEC2 gene probably underlay the X-linked mental retardation in this child. Above finding has, expanded the spectrum of IQSEC2 gene mutations and provide a basis for the diagnosis of similar cases.
Female ; Guanine Nucleotide Exchange Factors/genetics* ; Heterozygote ; Humans ; Intellectual Disability/genetics* ; Mental Retardation, X-Linked/genetics* ; Mutation ; Phenotype

Fragile X syndrome (FXS) is the most common monogenic form of inherited intellectual disability and autism spectrum disorder (ASD). More than 99% of individuals with FXS are caused by the unstable expansion of CGG repeats located within the 5'-untranslated region of the FMR1 gene. The clinical features of FXS include various degrees of cognitive deficit, physical, behavioral and psychiatric problems. Early treatment and prevention from having further affected children can be guided by molecular genetic testing of the FMR1 gene. The following guideline has combined the relevant research, guidelines and consensus worldwide, and summarized the genetic knowledge and clinical treatment for FXS in order to achieve a standardized diagnosis, treatment and prevention for patients and families affected by this disease.
Child ; Humans ; Autism Spectrum Disorder/therapy* ; Fragile X Mental Retardation Protein/genetics* ; Fragile X Syndrome/therapy* ; Intellectual Disability/genetics*