Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.

Background: We previously performed targeted sequencing of autism risk genes in probands from the Autism Clinical and Genetic Resources in China (ACGC) (phase I). Here, we expand this analysis to a larger cohort of patients (ACGC phase II) to better understand the prevalence, inheritance, and genotype-phenotype correlations of likely gene-disrupting (LGD) mutations for autism candidate genes originally identified in cohorts of European descent.

Methods: We sequenced 187 autism candidate genes in an additional 784 probands and 85 genes in 599 probands using single-molecule molecular inversion probes.

A novel NHS mutation causes Nance-Horan Syndrome in a Chinese family.

Background: Nance-Horan Syndrome (NHS) (OMIM: 302350) is a rare X-linked developmental disorder characterized by bilateral congenital cataracts, with occasional dental anomalies, characteristic dysmorphic features, brachymetacarpia and mental retardation. Carrier females exhibit similar manifestations that are less severe than in affected males.

Methods: Here, we report a four-generation Chinese family with multiple affected individuals presenting Nance-Horan Syndrome.

Phenotypic expansion of the interstitial 16p13.3 duplication: a case report and review of the literature.

Genotype-phenotype analysis of at least 25 individuals with interstitial 16p13.3 duplications defines a recognizable syndrome associated with duplication of a critical Rubinstein-Taybi region encompassing only the CREBBP gene. Nevertheless, variable or incompletely penetrant phenotype has been reported previously.

Disruption of Contactin 4 in two subjects with autism in Chinese population.

Autism is a heterogeneous childhood neurodevelopmental disorder that is characterised by deficits in verbal communication, impaired social interactions, restricted interests and repetitive behaviours. Using an Illumina HumanCNV370-Quad BeadChip, we identified two Han Chinese individuals with autism and large duplications (~1.6 Mb and ~2.

A novel splicing mutation in COL1A1 gene caused type I osteogenesis imperfecta in a Chinese family.

Osteogenesis imperfect (OI) is a heritable connective tissue disorder with bone fragility as a cardinal manifestation, accompanied by short stature, dentinogenesis imperfecta, hyperlaxity of ligaments and skin, blue sclerae and hearing loss. Dominant form of OI is caused by mutations in the type I procollagen genes, COL1A1/A2. Here we identified a novel splicing mutation c.

[Linkage analysis of susceptibility loci in 2 target chromosomes in pedigrees with paranoid schizophrenia and undifferentiated schizophrenia].

Objective: To investigate the relationship of susceptibility loci in chromosomes 1q21-25 and 6p21-25 and schizophrenia subtypes in Chinese population.

Methods: A genomic scan and parametric and non-parametric analyses were performed on 242 individuals from 36 schizophrenia pedigrees, including 19 paranoid schizophrenia and 17 undifferentiated schizophrenia pedigrees, from Henan province of China using 5 microsatellite markers in the chromosome region 1q21-25 and 8 microsatellite markers in the chromosome region 6p21-25, which were the candidates of previous studies. All affected subjects were diagnosed and typed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised (DSM-IV-TR; American Psychiatric Association, 2000).

FBXO7 gene mutations may be rare in Chinese early-onset Parkinsonism patients.

A recent study has shown that FBXO7 is a causative gene for PARK15-linked autosomal recessive early-onset Parkinsonism which was described by Davison for the first time in 1954 and known as Pallido-Pyramidal Disease or Parkinsonia-Pyramidal Syndrome in the past. In order to investigate the characteristics of FBXO7 gene mutations in Chinese early-onset Parkinsonism patients, we performed polymerase chain reaction and DNA direct sequencing on 135 patients and 200 controls. In this study, we found 10 polymorphisms including two novel polymorphisms (-274G-->C, c.

Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population.

Objectives: Autism is a neurodevelopmental disorder, and genetic factors play an important role in its pathogenesis. Earlier findings suggest the CNTNAP2 as a predisposition locus of autism, but no study has been carried out on the possible association of CNTNAP2 with autism in the Chinese Han population.

Methods: In this study, three single nucleotide polymorphisms located within the CNTNAP2 were genotyped in 185 Chinese Han autistic families by polymerase chain reaction-restriction fragment length polymorphism analysis, followed by a transmission disequilibrium test.

[Identification of the small supernumerary marker chromosomes in two patients with Turner syndrome].

Objective: To identify the small supernumerary marker chromosomes (sSMC) and guide the genetic counseling and medical treatment in two patients with Turner syndrome.

Methods: High resolution GTG and C banding, SRY amplification by PCR and fluorescence in situ hybridization (FISH) on metaphase chromosomes were performed to the two patients.

Results: The karyotypes of the two patients were 45, X [29]/46,X, +mar[31] and 45,X[71]/46,X, +mar[29] respectively.

Analysis of SCA2 and SCA3/MJD repeats in Parkinson's disease in mainland China: genetic, clinical, and positron emission tomography findings.

To investigate the prevalence and clinical feature(s) of Parkinson's disease (PD) patients with expanded (ATXN2 and MJD1) genes of spinocerebellar ataxia type 2 and 3 (SCA2 and SCA3/MJD) in a mainland Chinese population, CAG triplet repeat expansions of (SCA2 and SCA3/MJD) genes (ATXN2 and MJD1) were analyzed in a cohort of 452 PD patients, including 386 sporadic and 66 familial forms. Striatal dopamine transporter was evaluated in two SCA2 and two SCA3/MJD-positive family members, an idiopathic PD patient and a healthy control using carbon (C11) [(11)C]-radiolabeled-CFT positron emission tomography (PET). We found two patients in one familial PD (FPD) family (1.

[Growing of human embryonic stem cells on feeders derived from themselves].

This study was carried out to determine whether mesenchymal stem cells (MSCs) derived from teratoma of human embryonic stem cells (hESCs) function as feeder cells to support hESCs growth. Approximately 5x10(6) hESCs were injected into the hind limb muscle of each SCID-beige mouse to form teratoma. After 8 weeks, the MSCs were isolated from the teratoma and cultured in Mesencult medium.

[Mutation screening of the dystrophin gene in 14 Chinese Duchenne/Becker muscular dystrophy patients without gross deletions].

Objective: To search for the dystrophin gene mutations of Duchenne muscular dystrophy (DMD) patients without gross deletions, in order to offer accurate genetic counseling and prenatal diagnosis for those families.

Methods: All 79 exons of the dystrophin gene as well as its 5'-UTR and 3'-UTR of 14 Chinese DMD/Becker muscular dystrphy (BMD) patients without detectable gross deletions were screened by denaturing high performance liquid chromatography (DHPLC) and heteroduplex fragments were identified by subsequent sequencing.

Results: Seven causative point mutations, including two novel ones, were detected in 7 patients.

Screening of LRRK2 interactants by yeast 2-hybrid analysis.

Objective: To isolate and identify the potential binding partners of LRRK2, a gene linked to both dominant familial form and sporadic form of Parkinson's disease, thus to further our knowledge of its function.

Methods: We used a sequence containing full-length of COR domain and part of ROC and MAPKKK domain as bait. The bait amplified by polymerase chain reaction (PCR) was then cloned into a yeast expression plasmid pGBKT7.

[Rapid prenatal diagnosis of chromosome aneuploidies in 60 uncultured amniotic fluid samples by fluorescence in situ hybridization].

Objective: To evaluate the feasibility of rapid prenatal diagnosis of chromosome aneuploidies by interphase fluorescence in situ hybridization (FISH) using uncultured amniotic fluid.

Methods: Bacterial artificial chromosome (BAC) DNA probes were prepared and validated by using cultured peripheral blood. Interphase FISH for chromosomes 13, 18, 21, X and Y was performed in 60 amniotic fluid samples for the rapid prenatal diagnosis of chromosome aneuploidies, and the results were compared with the karyotypes from conventional cytogenetic analysis.

[Biological characteristics and safety evaluation of endothelial progenitor cells from the umbilical cord blood].

Objective: To investigate the biological characteristics of endothelial progenitor cells (EPCs) from the umbilical cord blood (UCB), and to evaluate their oncogenicity after long-term culture in vitro.

Methods: The mononuclear cells (MNCs) were isolated from the UCB and cultured in MCDB131 medium supplemented with 20% FBS, VEGF and other growth factors. Morphology of the EPCs was observed, and the growth curve of the EPCs was investigated.

[Identification of the origin of marker chromosome by comparative genomic hybridization].

Objective: To identify the origin of the marker chromosome in a patient with chromosome aberration, and to provide the precise genetic diagnosis.

Methods: Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) were performed to detect the known small marker chromosome in this patient.

Results: The small marker chromosome originated from chromosome 13 pter->q12.

[Preimplantation genetic diagnosis of Duchenne muscular dystrophy by single cell triplex PCR].

Objective: To detect two exons of Duchenne muscular dystrophy (DMD) gene and a gender discrimination locus amelogenin gene by single cell triplex PCR, and to evaluate the possibility of this technique for preimplantation genetic diagnosis (PGD) in DMD family with DMD deletion mutation.

Methods: Single lymphocytes from a normal male, a normal female, two DMD patients (exon 8 and 47 deleted, respectively) and single blastomeres from the couples treated by the in vitro fertilization pre-embryo transfer (IVF-ET) and without family history of DMD were obtained. Exons 8 and 47 of DMD gene were amplified by a triplex PCR assay, the amelogenin gene on X and Y chromosomes were co-amplified to analyze the correlation between embryo gender and deletion status.

[Azoospermia factor microdeletion on Y chromosome in patients with idiopathic azoospermia or severe oligozoospermia].

Objective: To investigate the correlation between male infertility and Y chromosome microdeletions of azoospermia factor (AZF) regions, and to establish a reliable genetic diagnosis in idiopathic infertile male patients with azoospermia or severe oligozoospermia.

Methods: Multiplex PCR amplification of 6 sequence-tagged sites in AZF regions of the Y chromosome was examined among 100 normal karyotype male patients with azoospermia or oligozoospermia.

Results: Four patients (4%) had Y chromosome microdeletions, the microdeletions of 3 patients were idiopathic azoospermic and those of the other 1 patient were secretory azoospermia.

Molecular analysis of hearing loss associated with enlarged vestibular aqueduct in the mainland Chinese: a unique SLC26A4 mutation spectrum.

It has been shown that mutations in the SLC26A4 gene are involved in syndromic deafness characterized by congenital sensorineural hearing impairment and goitre (Pendred's syndrome), as well as in congenital isolated deafness (DFNB4), both of which are associated with enlarged vestibular aqueduct (EVA). The prevalence of SLC26A4 mutations in Pendred's syndrome is clearly established in many ethnic groups, but the data from Mainland Chinese patients with deafness and EVA remain poor. In this report, 15 patients from 13 unrelated Chinese families with deafness and EVA were analyzed for SLC26A4 using direct sequencing.