Genome-wide and Interaction Linkage Scan for Nonsyndromic Cleft Lip with or without Cleft Palate in Two Multiplex Families in Shenyang,China

Objectives To identify the loci involved in nonsyndromic cleft lip with or without cleft palate （NSCL/P） in Northern Chinese people in Shenyang by using genomewide and interaction linkage scan.Methods Two multiplex families in Shenyang from North China were ascertained through probands with NSCL/P.Blood of every member was drawn for DNA extraction and analysis.Genotypes were available for 382 autosomal short tandem repeat （STR） markers from the ABI Prism Linkage Mapping Set version 2.5.Linkage between markers and NSCL/P was assessed by 2-point parametric LOD scores,multipoint heterogeneity parametric LOD scores （HLODs）,and multipoint nonparametric linkage score （NPL）.Results The initial scan suggested linkage on Chromosomes 1,2,and 15.In subsequent fine mapping,1q32-q42 showed a maximum multipoint LOD score of 1.9（empirical P=0.013） and an NPL score of 2.35 （empirical P=0.053）.For 2p24-p25,the multipoint NPL increased to 2.94 （empirical P=0.007）.2-locus interaction analysis obtained a maximum NPL score of 3.73 （P=0.00078） and a maximum LOD score of 3 for Chromosome 1 （at 221 cM） and Chromosome 2 （at 29 cM）.Conclusion Both parametric and nonparametric linkage scores greatly increased over the initial linkage scores on 1q32-q42,suggesting a susceptibility locus in this region.Nonparametric linkage gave a strong evidence for a candidate region on chromosome 2p24-p25.The superiority of 2-locus linkage scores compared to single-locus scores gave additional evidence for linkage on 1q32-q42 and 2p24-p25,and suggested that certain genes in the two regions may contribute to NCSL/P risks with interaction.

Causes of severe neonatal hyperbilirubinemia: a multicenter study of three regions in China

Background Available evidence suggests that our country bear great burden of severe hyperbilirubinemia.However,the causes have not been explored recently in different regions of China to guide necessary clinical and public health interventions.Methods This was a prospective,observational study conducted from March 1,2018,to February 28,2019.Four hospitals in three regions of China participated in the survey.Data from infants with a gestational age≥35 weeks,birth weight>2000 g,and total serum bilirubin(TSB)level≥17 mg/dL(342μmol/L)were prospectively collected.Results A total of 783 cases were reported.Causes were identified in 259 cases.The major causes were ABO incompatibility(n=101),glucose-6-phosphate dehydrogenase deficiency(n=76),and intracranial hemorrhage(n=70).All infants with glucose-6-phosphate dehydrogenase deficiency were from the central south region.Those from the central south region had much higher peak total bilirubin levels[mean,404μmol/L;standard deviation(SD),75μmol/L]than those from the other regions(mean,373μmol/L;SD,35μmol/L)(P<0.001).Conclusions ABO incompatibility was the leading cause in the east and northwest regions,but cases in the central south region were mainly caused by both ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency,and infants in this region had a much higher peak total bilirubin level.Intracranial hemorrhage may be another common cause.More thorough assessments and rigorous bilirubin follow-up strategies are needed in the central south region.