Effect of MSX1 on the cellular function of cardiomyocytes.

MSX1 (Muscle Segment Homeobox 1) has pleiotropic effects in various tissues, including cardiomyocytes, while the effect of MSX1 on cardiomyocyte cellular function was not well known. In this study, we used AC16 cell culture, real-time fluorescence quantitative PCR (qPCR), protein blotting (Western blot), flow cytometry apoptosis assay and lactate dehydrogenase (LDH) ELISA (Enzyme-Linked Immunosorbnent Assay) to investigate the effect of the MSX1 gene on cardiomyocyte function. The results showed that MSX1 plays a protective role against hypoxia of cardiomyocytes. However, further studies are required to fully understand the role of MSX1 in the regulation of LDH expression in different cell types and under different conditions.

Copy number variations independently induce autism spectrum disorder.

The examination of copy number variation (CNV) is critical to understand the etiology of the CNV-related autism spectrum disorders (ASD). DNA samples were obtained from 64 ASD probands, which were genotyped on an Affymetrix CytoScan HD platform. qPCR or FISH were used as a validation for some novel recurrent CNVs. We further compared the clinical phenotypes of the genes in the Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources (DECIPHER) database with these overlapping genes. Using vast, readily available databases with previously reported clinically relevant CNVs from human populations, the genes were evaluated using Enrichment Analysis and GO Slim Classification. By using the Ploysearch2 software, we identified the interaction relationship between significant genes and known ASD genes. A total of 29 CNVs, overlapping with 520 genes, including 315 OMIM genes, were identified. Additionally, myocyte enhancer factor 2 family (MEF2C) with two cases of CNV overlapping were also identified. Enrichment analysis showed that the 520 genes are most likely to be related to membrane components with protein-binding functions involved in metabolic processes. In the interaction network of those genes, the known ASD genes are mostly at the core position and the significant genes found in our samples are closely related to the known ASD genes. CNVs should be an independent factor to induce autism. With the strategy of our study, we could find the ASDs candidate genes by CNV data and review certain pathogenesis of this disorder. Those CNVs were associated with ASD and they may contribute to ASD by affecting the ASD-related genes.

Analysis of hematological phenotype and genotype of 23 patients from Guangdong with co-inherited hemoglobin Hb Westmead and β-thalassemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the genotype-phenotype correlation among carriers from Guangdong with co-inherited hemoglobin Hb Westmead (HbWS) and β-thalassemia.</p><p><b>METHODS</b>Twenty three patients (including 9 males and 14 females, aged 1-53 year old) were diagnosed by hematological analysis and genetic testing. Complete blood cell count and hemoglobin electrophoresis analysis were performed on a XE4000i automatic hemocyte analyzer. Hb, HbF and HbA2 were tested by high performance liquid chromatography (HPLC). Gap-PCR was adopted to detect three common thalassemia deletions. Reverse dot-blotting (RDB) assay was applied for detecting three common non-deletional α2 gene mutations and β-thalassemia.</p><p><b>RESULTS</b>Among the 23 patients, 12 showed anemia, among whom 9 had mild anemia and 3 had moderate anemia. The lowest Hb was 68 g/L, and both mean corpuscular volume and mean corpuscular hemoglobin were lower than average, while HbA2 was higher than 3.5%. Genetic analysis confirmed that 5 cases had αWS-α/α-α, β CD654/β N (21.7%), 4 had α WS-α/α-α, β CD41-42/β N (17.4%), 5 had α WS-α/α-α, β CD17/β N (21.7%), 4 had α WS-α/α-α, β CD28/β N (17.4%), 1 had α WS-α/α-α, β CD71-72/β N (4.3%), 1 had αWS-α/α-α, β CD27-28/β N (4.3%), 1 had α WS-α/α-α, β CD41-42/β CD17 (4.3%), 2 had a concomitant β-thalassemia heterozygosity and -α 3.7 deletion.</p><p><b>CONCLUSION</b>Patients with co-existing Hb WS and other β-thalassemia trait may show variable clinical features. Such compound heterozygotes are usually misdiagnosed during screening by hemoglobin electrophoresis, accurate diagnose should be attained by molecular diagnosis.</p>

Prader-Willi syndrome with a long-contiguous stretch of homozygosity not covering the critical region.

Prader-Willi syndrome is a common and complex disorder affecting multiple systems. Its main manifestations are infantile hypotonia with a poor sucking reflex, a characteristic facial appearance, mild mental retardation, hypogonadism and early-onset obesity. Prader-Willi syndrome is due to the absence of paternally expressed imprinted genes at 15q11.2-13, and 3 main mechanisms are known to be involved in its pathogenesis: paternal microdeletions, maternal uniparental disomy events, and imprinting defects. DNA methylation analysis can detect almost all individuals with Prader-Willi syndrome but is unable to distinguish between the molecular classes of the disease. Thus, additional methods are necessary to identify the molecular classes. Here, we employed chromosomal microarray analysis-single nucleotide polymorphism for diagnosis and detected a long-contiguous stretch of homozygosity on chromosome 15, which is highly predictive of maternal uniparental disomy on chromosome 15. Other methods, including fluorescence in situ hybridization, chromosomal microarray analysis-comparative genomic hybridization, genotyping and family linkage analysis, were performed for further validation. In conclusion, our study highlights the use of long-contiguous stretch of homozygosity detection for the diagnosis of Prader-Willi syndrome.

Prenatal diagnosis of pure partial monosomy 18p associated with holoprosencephaly and congenital heart defects.

We applied CMA to detect chromosomal variations during a prenatal diagnosis and detected a 4.5Mb pure microdeletion at 18p11.3 that was not detected by conventional karyotyping. Fluorescent in situ hybridization (FISH) analysis was performed to confirm the deletion. Accurate breakpoints of the deletion in this patient were used to build correlations between monosomy 18p and the concomitant phenotypes, particularly holoprosencephaly (HPE), which is rarely reported in monosomy 18p11.3.