Non-immune factors are the most common cause of hydrops fetalis, which may manifest as abnormal accumulation of fluid in the body cavities. Hydrops fetalis is a complex condition with a high mortality rate. The prognosis is depending on the underlying disease and is particularly poor in those with chromosomal aberrations or monogenic disorders. In this paper, advance in the research on non-immune hydrops fetalis is reviewed.

Thiamine, also known as vitamin B1, is an important vitamin for the body. The activated form of thiamine pyrophosphate is involved in cell metabolism as an important co-enzyme. Defects of thiamine transport and activation may cause lack of thiamine and affection of cell metabolism, leading a variety of diseases. This review has summarized defects of thiamine transport and activation and related diseases.

OBJECTIVE To assess the association of SLC12A3 and SCNN1B gene polymorphisms (rs11643718 and rs12447134) with essential hypertension among ethnic Koreans from Mudanjiang, China. METHODS For 204 patients with essential hypertension and 186 healthy controls, the genotypes of rs11643718 and rs12447134 loci were determined with an improved multiplex ligase detection reaction (iMLDR) method. RESULTS Allelic and genotypic frequencies of rs11643718 of SLC12A3 gene are associated with the onset of disease hypertension (P <0.05) as well as systolic blood pressure (P < 0.01, under a recessive model). No association was found between rs12447134 of SCNN1B gene with the onset of disease (P > 0.05) but diastolic blood pressure (P < 0.05, under a recessive model). CONCLUSION The polymorphisms of rs11643718 locus is associated with the susceptibility for essential hypertension among ethnic Koreans from Mudanjiang area and can be used as a predictor for the disease.

OBJECTIVE To assess the association of polymorphisms of KIR2DL4 gene with leukemia among ethnic Hans from southern China. METHODS A total of 590 leukemia patients were recruited, which included 283 cases of acute lymphoblastic leukemia (ALL), 277 cases of acute myeloid leukemia (AML), and 80 cases of chronic myeloid leukemia (CML). Meanwhile, 306 healthy controls were randomly selected from volunteer blood donors. Both groups were subjected to sequence-based typing of the entire coding sequence of the KIR2DL4 gene using an in-house assay. The genotype for each sample was determined with Assign 4.7 SBT software. The frequencies of each detected KIR2DL4 allele, the 9A type KIR2DL4 allele and 10A type KIR2DL4 allele of the ALL, AML and CML groups were compared with those of the control group. RESULTS Five KIR2DL4 alleles, namely KIR2DL4*001, *005, *006, *008 and *011, were detected in the ALL, AML and CML groups as well as the control group. A significant difference was detected in the frequencies of KIR2DL4*011 and 10A type KIR2DL4 allele between the ALL group and the control group (KIR2DL4*011: OR = 1.66, P = 0.01; 10A type KIR2DL4: OR = 0.42, P = 0.03), but was lost after P correction (Pc > = 0.05). No significant difference was detected in the frequencies of KIR2DL4 alleles, the 9A type KIR2DL4 and 10A type KIR2DL4 allele between the AML and CML patient groups compared with the control group (P > 0.05, Pc > 0.05). CONCLUSION The allelic diversity of the KIR2DL4 locus showed no significant association with leukemia among ethnic Hans from southern China.

OBJECTIVE To assess the association of single nucleotide polymorphisms (SNPs) of the T-cadherin (CDH13) gene with metabolic syndrome (MS) among ethnic Han Chinese.METHODS Genotypes of 6 SNPs(rs11646213, rs12596316, rs3865188, rs12444338, rs12051272, and rs7195409) of the CDH13 gene among 453 patients with MS and 526 controls were determined with a TaqMan method, and their association with MS was assessed. RESULTS For 5 SNPs (rs11646213, rs3865188, rs12444338, rs12051272, and rs7195409), no difference was found in allelic and genotypic frequencies of the CDH13 gene between the two groups. Comparing with rs12596316 (AA+GG) genotype, rs12596316 AG genotype has significantly increased the risk of MS(P = 0.01,OR = 1.38,95%CI: 1.07-1.78), though no association was found between particular alleles of the rs12596316 with MS.There was no difference in the frequencies of rs11646213-rs12596316-rs3865188-rs12444338-rs12051272 haplotype between the two groups(P > 0.05). CONCLUSION No association was found between the five SNPs (rs11646213, rs3865188, rs12444338, rs12051272 and rs7195409) of the CDH13 gene with the MS, while the rs12596316AG genotype of the CDH13 gene is associated with the susceptibility to MS among ethnic Han Chinese.

OBJECTIVE To analyze the clinical features and genetic mutations in a neonate with atypical Cri-du-chat syndrome, whom only featured with weak cry but had no dysmorphic facial features and congenital heart disease. METHODS G-banding karyotyping was performed on the child and her parents. The result was validated by fluorescence in situ hybridization (FISH). Chromosome microarray (CMA) was used to further delineate the mutation. RESULTS G-banding analysis suggested that the child had a karyotype of 46,XX,del(5)(p14p15), while both of his parents had a normal karyotype. FISH confirmed the absence of D5S23 and D5S721 at 5p15.2. A 25.7 Mb deletion was detected in the 5p15.33p14.1 region by CMA. CONCLUSION The phenotype of Cri-du-chat syndrome can vary significantly among patients, particularly in neonates, and can be easily mis-diagnosed. Combined cytogenetic and molecular analysis can identify the missing fragments with greater precision.

OBJECTIVE To identify potential mutation in a patient with cutis laxa through exome sequencing of genetic disease-related genes and explore its clinical and genetic features. METHODS Clinical data was collected for the proband and her parents. Exome sequencing was carried out on the proband. Suspected mutations were verified by Sanger sequencing. RESULTS Exome sequencing identified a compound heterozygous mutation of the ATP6V0A2 gene, c.187C>T (p.R63X) and c.1189G>C (p.A397P), in the proband. The mutations were respectively inherited from the father and mother. The patient was diagnosed with autosomal recessive cutis laxa type 2A (ARCL2A). CONCLUSION A case with ARCL2A was diagnosed. The novel mutation has expanded the spectrum of ATP6V0A2 mutations. Exome sequencing is a useful tool for the diagnosis of complex genetic diseases.

OBJECTIVE To assess the value of whole genome sequencing for the identification of de novo structural chromosomal abnormalities. METHODS Whole genome sequencing was utilized to analyze a boy with a peripheral blood karyotype of 46,XY,ins(3)(q21p13p21). The patient manifested with ocular abnormalities including blepharophimosis and ptosis. RESULTS Whole genome sequencing suggested a fragmentation of chromosome 3 (from position 55 473 257 to 78 341 929) has been inserted into between 136 876 730 to 138 643 831, and the breakpoints have occurred in the intergenic region. Meanwhile, there was a deletion between 138 643 831 and 138 694 476. This region contains FOXL2, a pathogenic gene associated with blepharophimosis-ptosis-epicanthus inversus syndrome. CONCLUSION De novo structural chromosomal abnormalities may be caused by novel breakpoints or microdeletion flanking the deletion region. To confirm its pathogenic nature, a mutation needs to be assessed at both genetic and genomic levels, for which whole genome sequencing is a good option.

OBJECTIVE To detect potential mutations of the EXT1 and EXT2 genes in a pedigree affected with hereditary multiple exostosis (HME). METHODS For a four-generation family with 7 affected individuals from 17 family members,genomic DNA was extracted from peripheral venous blood samples. All exons of the EXT1 and EXT2 genes were screened for potential mutation by PCR and Sanger sequencing. RESULTS A novel heterozygous frameshift mutation c.1202delT (p.I401Tfs*2)was found in exon 4 of the EXT1 gene in the proband and the other 6 affected individuals. The same mutation was not detected among the healthy members from the family. The mutation has given rise a truncated EXT1 protein with loss of 345 amino acids. CONCLUSION A novel frameshift mutation of the EXT1 gene has been identified in a pedigree affected with HME, which has enriched the mutational spectrum of the EXT1 gene and may facilitate genetic counseling and prenatal diagnosis for the family.

OBJECTIVE To explore the genetic basis for a family affected with Peutz-Jeghers syndrome (PJS). METHODS Genomic DNA was extracted from peripheral blood and oral swab samples from the patient and her relatives. Next-generation sequencing (NGS) was used to analyze 106 target genes by capturing the exons and adjacent intronic regions. Suspected pathogenic mutation was verified by NGS. RESULTS A missense STK11 mutation was detected in the proband, which was not reported previously. The mutation has caused substitution of Leucine by Proline. NGS has detected the same mutation in the mother but not among other relatives. CONCLUSION This hereditary case of PJS may be attributed to the missense mutation of the STK11 gene.