Comparison of low density lipoprotein cholesterol concentrations by direct measurement and Friedewald formula in diabetic patients with and without hemoglobin E disorders.

J Med Assoc Thai. 2013 Apr;96(4):407-15

Authors: Srisurin W

Abstract
BACKGROUND: Low density lipoprotein cholesterol (LDL) levels were significantly lower in diabetic patients with homozygous hemoglobin E (HbEE) measured by a homogeneous assay.
OBJECTIVE: Comparison of direct measurement of LDL (dLDL) determined by a homogeneous assay and calculated LDL (cLDL) determined by the Friedewald formula in diabetic patients with and without hemoglobin E disorders.
MATERIAL AND METHOD: The hemoglobin E (HbE) screening test and hemoglobin (Hb) typing were conducted in diabetic patients at Surin Hospital. In 2,973 cases with triglyceride (TG) levels under 400 mg/dL, classification was determined into three groups, negative screening (NS), HbE trait (HbEA), and HbEE. The measurements of total cholesterol (TC) and TG were performed using enzymatic methods. The direct measurements of high density lipoprotein cholesterol (HDL) andLDL were performed using homogeneous methods.
RESULTS: The prevalence of HbEE and HbEA were 7.6% and 35.7% respectively. The means of TG, CHOL, dLDL, cLDL, and non-HDL cholesterol (non-HDL-C) were significantly lower in HbEE (p = 0.009, p<0.001, p< 0.001, p< 0.001, and p< 0.001 respectively). The mean of cLDL in each group was significantly lower than the mean of dLDL (p< 0.001 at all). By the Passing-Bablok regression, the interception with 95% confidence interval (95% CI) ofNS, HbEA, and HbEE were 4.322 (3.082 to 5.485), 6.625 (5.094 to 7.981), and 6.60 (3.347 to 10.356) respectively. The slope with 95% CI were 1.017 (1.007 to 1.027), 1.002 (0.991 to 1.016), and 1.0 (0.963 to 1.033) respectively. Using the Bland-Altman method, the mean with standard deviation of the difference between dLDL and cLDL in NS, HbEA, and HbEE were 6.758 (7.856) mg/dL, 7.350 (8.212) mg/dL, and 7.225 (7.129) mg/dL respectively. The 95% limits of agreement between the dLDL and cLDL in NS, HbEA, and HbEE were -8.640 to 22.156 mg/dL, -8.746 to 23.446 mg/dL, and-6.748 to 21.197 mg/dL respectively. The statistically significant difference of having more patients with cLDL <100 mg/dL than dLDL <100 mg/dL in each group were observed in most of the subgroups of TG levels at 100 mg/dL to <200 mg/dL and higher HbEE had more patients of dLDL <100 mg/dL and cLDL <100 mg/dL than NS. The adjusted odds ratio and 95% CI were 1.383 (1.022 to 1.871) with p = 0. 036 and 1.838 (1.375 to 2.456) with p< 0.001 respectively.
CONCLUSION: The direct homogeneous method showed a higher LDL concentration than the Friedewald formula indicated in diabetes and diabetes with HbE disorders. The percentage of higher LDL levels by direct method than Friedewald formula significantly increased along the subgroups of higher TG levels. The dissociation occurred at TG levels of 100 mg/dL and higher Systematic biases between both methods were found in all groups but the proportional difference between both methods was only observed in diabetes without HbE disorders.

PMID: 23691694 [PubMed - in process]

Combined array CGH plus SNP genome analyses in a single assay for optimized clinical testing.

Eur J Hum Genet. 2013 May 22;

Authors: Wiszniewska J, Bi W, Shaw C, Stankiewicz P, Kang SH, Pursley AN, Lalani S, Hixson P, Gambin T, Tsai CH, Bock HG, Descartes M, Probst FJ, Scaglia F, Beaudet AL, Lupski JR, Eng C, Wai Cheung S, Bacino C, Patel A

Abstract
In clinical diagnostics, both array comparative genomic hybridization (array CGH) and single nucleotide polymorphism (SNP) genotyping have proven to be powerful genomic technologies utilized for the evaluation of developmental delay, multiple congenital anomalies, and neuropsychiatric disorders. Differences in the ability to resolve genomic changes between these arrays may constitute an implementation challenge for clinicians: which platform (SNP vs array CGH) might best detect the underlying genetic cause for the disease in the patient? While only SNP arrays enable the detection of copy number neutral regions of absence of heterozygosity (AOH), they have limited ability to detect single-exon copy number variants (CNVs) due to the distribution of SNPs across the genome. To provide comprehensive clinical testing for both CNVs and copy-neutral AOH, we enhanced our custom-designed high-resolution oligonucleotide array that has exon-targeted coverage of 1860 genes with 60 000 SNP probes, referred to as Chromosomal Microarray Analysis - Comprehensive (CMA-COMP). Of the 3240 cases evaluated by this array, clinically significant CNVs were detected in 445 cases including 21 cases with exonic events. In addition, 162 cases (5.0%) showed at least one AOH region >10 Mb. We demonstrate that even though this array has a lower density of SNP probes than other commercially available SNP arrays, it reliably detected AOH events >10 Mb as well as exonic CNVs beyond the detection limitations of SNP genotyping. Thus, combining SNP probes and exon-targeted array CGH into one platform provides clinically useful genetic screening in an efficient manner.European Journal of Human Genetics advance online publication, 22 May 2013; doi:10.1038/ejhg.2013.77.

PMID: 23695279 [PubMed - as supplied by publisher]

A novel homozygous mutation of GJC2 derived from maternal uniparental disomy in a female patient with Pelizaeus-Merzbacher-like disease.

J Neurol Sci. 2013 May 16;

Authors: Shimojima K, Tanaka R, Shimada S, Sangu N, Nakayama J, Iwasaki N, Yamamoto T

Abstract
Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating disorder of the central nervous system characterized by nystagmus, motor developmental delay, ataxia, and progressive spasticity. The gap junction protein gamma-2 gene (GJC2), encoding the gap junction protein connexin 47, is one of the genes responsible for this condition. In this study, a novel homozygous mutation in GJC2 (c.746C>G; p.P249R) was identified in a 21-year-old female patient with PMLD. Although her mother was a carrier of this mutation, the Mendelian inheritance pattern could not be determined because the paternal sample was unavailable. Alternatively, chromosomal microarray testing together with single nucleotide polymorphism typing (CGH+SNP) was performed to determine the gene copy number and analyze the haplotype in the 1q42.13 region in which GJC2 is located. The result showed no deletion, but the GJC2 region was involved in the loss-of-heterozygosity region. Furthermore, haplotype of chromosome 1, in which GJC2 is located, revealed that both copies of chromosome 1 were derived from the patient's mother, indicating maternal uniparental disomy of chromosome 1. This study showed the advantage of the SNP genotyping microarray for detecting the origin of the mutation.

PMID: 23684670 [PubMed - as supplied by publisher]

Pregnancy outcomes amongst thalassemia traits.

Arch Gynecol Obstet. 2013 May 17;

Authors: Hanprasertpong T, Kor-Anantakul O, Leetanaporn R, Suntharasaj T, Suwanrath C, Pruksanusak N, Pranpanus S

Abstract
OBJECTIVE: To compare the pregnancy outcome between pregnancies affected and not affected by thalassemia trait. METHODS: A retrospective case-control cohort study was conducted on singleton pregnant women who attended antenatal care and delivered at Songklanagarind Hospital. All of the participating thalassemia trait pregnant women were diagnosed based on hemoglobin typing and/or DNA analysis. A ratio of around 1-1 was used to compare their pregnancy outcomes with normal pregnant women. RESULTS: Seven hundred thirty-nine thalassemia trait and 799 normal pregnant women were included in the study. All of the women were Thai nationals living in the Southern Region of Thailand and nearly all of them had spontaneously conceived. Maternal complication rates of gestational diabetes, preterm birth, antepartum bleeding, postpartum bleeding, shoulder dystocia and puerperal morbidity, and the rates of neonatal complications: macrosomia, fetal weight <2,000 g, intrauterine growth restriction (IUGR), stillbirth, low Apgar score (<7) at 1 and 5 min and NICU admission, were not significantly different between the two groups. The rate of pre-eclampsia, however, was significantly different, with RRs of 1.73 (CI 1.01-3.00). CONCLUSION: The thalassemia trait condition did not affect the risk of gestational diabetes, postpartum hemorrhage, stillbirth, preterm birth and puerperal morbidity. However, pre-eclampsia should be warranted especially among nulliparous and high-BMI pregnant women.

PMID: 23681496 [PubMed - as supplied by publisher]