OBJECTIVETo identify pathogenic mutation in a pedigree affected with craniofacial and skeletal abnormalities featuring an autosomal dominant inheritance.

METHODSClinical data and peripheral venous blood samples of the pedigree were collected. A total of 326 exons of skeletal disease-related genes were screened using Roche NimbleGen probes, and the results were confirmed by Sanger sequencing. Suspected variants were analyzed by bioinformatic software.

RESULTSA novel heterozygous mutation c.480C>A (p.160K>N) of HDAC4, the pathogenic gene for brachydactyly mental retardation syndrome, was found in the affected proband, his father and uncle. The proband and his father also carried a novel heterozygous c.880-882delAAG (p.294delK) mutation of TRPS1, the pathogenic gene for tricho-rhino-phalangeal syndrome. Bioinformatic analysis suggested that both mutations are pathogenic. In addition, three novel genetic variants, namely c.4817G>A (p.1606S>L) of MLL2, c.83A>G (p.28H>R) of TP63, and c.1712G>C (p.571T>S) of ERCC2, were also identified in this family.

CONCLUSIONThe HDAC4 c.480C>A (p.160K>N) mutation probably underlies the disease in this pedigree, while the TRPS1 c.880-882delAAG (p.294delK) mutation may be related with certain features of the affected family members. Genetic analysis has facilitated the diagnosis of this complex disease.

Asian Continental Ancestry Group ; genetics ; Craniofacial Abnormalities ; genetics ; Female ; Genetic Testing ; methods ; Heterozygote ; Humans ; Infant ; Male ; Mutation ; genetics ; Pedigree

OBJECTIVETo analyze the clinical phenotypes of a pedigree affected with periodic paralysis and explore its molecular basis.

METHODSClinical data and peripheral blood samples of the pedigree were collected. The proband and his father both complained of periodic paralysis and dysmorphic features. The exome of the proband was screened using Roche NimbleGen probes, and the results were confirmed by Sanger sequencing. Suspected mutations were subjected to bioinformatic and gene-disease correlation analysis.

RESULTSA c.653G>A (p.R218Q) mutation of the KCNJ2 gene was detected in both the proband and his father. Bioinformatics analysis suggested it to be pathogenic.

CONCLUSIONThe clinical manifestation of the pedigree was suggestive of Andersen-Tawil syndrome. KCNJ2 c.653G>A (p.R218Q) was the pathogenic mutation in this pedigree.

Objective To investigate insulin resistance and first-phase insulin secretion among the obese children with normal glucose tolerance,impaired glucose tolerance (IGT) and type 2 diabetes mellitus(T2DM) and to further explore their effects on children with T2DM.Methods Both physical examination and oral glucose tolerance test (OGTT) were performed to determine the glucose tolerance levels on a total of 87 subjects.They were divided into normal glucose tolerance group,IGT group and T2DM group according to their glucose tolerance levels.Insulin resistance and insulin secretion were represented by insulin sensitivity index (IAI) and △ I30/△ G30 =(I30min-I0min) /(G30 min-G0 min),respectively.SPSS software version 10.0 was used for statistical analysis.Differences from the groups were assessed by performing One-way ANOVA,and P ＜ 0.01 was considered significant.Results Among 87 subjects,52 cases turned out to have normal glucose tolerance (normal glucose tolerance group),16 cases were with IGT (IGT group) and 19 cases were with T2DM (T2DM group),respectively.The groups of normal glucose tolerance,IGT and T2DM were found to have the IAI values of-4.36 ±0.79,-4.80 ±0.56 and-4.73 ±0.53,respectively,which indicated that the IAI value of normal glucose tolerance group was significantly higher than those in both IGT and T2DMgroups(F =5.28,P ＜ 0.01),while there was no significant difference between the 2 groups of IGT and T2DM.The △I30/△G30 values of the obesity,IGT and T2DM groups were also indicated as 57.02-± 30.20,28.19 ± 23.47 and 11.65 ± 7.50,respectively,and therefore it could be revealed that the △ I30/△ G30 value of the IGT and T2DM groups were both significantly lower than that of the normal glucose tolerance group (F =47.90,P ＜ 0.01).Conclusions Both insulin sensitivity and first-phase insulin secretion respectively show statistically significant decrease in IGT andT2DM groups compared with those in obesity group,which indicates that they both may play important roles in diabetes onset in children.