Objective To investigate the role of double contrast-enhanced ultrasonography (DCUS) in the diagnosis of rectal gastrointestinal stromal tumors (GISTs). Methods In eleven patients with rectal GISTs before surgery, gastrointestinal ultrasound contrast agent were injected into rectal lumen and tumor’s two dimensional ultrasound features were analyzed. Microbubbles were injected into the vein to investigate the feature of lesion microcirculation perfusion. After the surgery, according to the tumor diameter and mitotic count, rectal GISTs were classified as very low-risk, low-risk, intermediated-risk and high-risk tumors. The very low-risk and low-risk tumors were grouped together as one group while the intermediated-risk and high-risk tumors were grouped together as another group. According to ultrasound performance and pathological type, ultrasonic features of rectal GISTs with different risk levels were estimated. Results Among all rectal GISTs cases, 63.6%(7/11) were low-risk. Under DCUS, the tumor diameter was less than 5 cm, with regular round, hypoechogenicity, uniform low enhancement and less internal liquefaction necrosis. For the 36.4%(4/11) high-risk cases, under DCUS, the tumor diameter was≥5 cm, with irregular round or lobulation, mixed hyperechogenicity and hypoechogenicity, nonuniform high enhancement, large blood vessel and common liquefied necrosis region. The biological behavior of rectal GISTs was relevant to lesion size, liquefaction necrosis and enhancement mode of ultrasound contrast and irrelevant to the bound and shape of lesion. The accuracy of DCUS and contrast-enhanced ultrasonography were 90.9%(10/11) and 72.7%(8/11) respectively. Conclusions DCUS is considered as an effective tool in diagnosingrectal GISTs and can get useful information of the biological characteristics. It has great value for the diagnosis and treatment of rectal GISTs.

OBJECTIVE: To explore the genotype-phenotype correlation in a child with Kabuki syndrome type 1 (KS1) caused by a mosaic frameshift variant of KMT2D gene. METHODS: Trio-based whole exome sequencing (WES) was carried for the patient and her parents. Candidate variant was verified by Sanger sequencing. RESULTS: The proband, a 3-year-and-2-month-old Chinese girl, presented with distinctive facial features, cognitive impairment, mild developmental delay, dermatoglyphic abnormalities, minor skeletal anomalies, ventricular septal defect, and autistic behavior. Trio-based WES revealed that the proband has carried a de novo mosaic frameshit variant of the KMT2D gene, namely NM_003482.3:c.13058delG (p.Pro4353Argfs*31) (GRCh37/hg19), for which the mosaicism rate was close to 21%. The variant was unreported previously and was confirmed by Sanger sequencing. Chromosomal microarray analysis (CMA) has revealed no pathogenic or likely pathogenic copy number variations. Compared with previously reported cases, our patient has presented obvious behavior anomalies including autism, anxiety and sleep problems, which were rarely reported. CONCLUSION This study has expanded the spectrum of KMT2D gene variants, enriched the clinical phenotypes of KS1, and facilitated genetic counseling for the family.
Abnormalities, Multiple ; China ; DNA Copy Number Variations ; DNA-Binding Proteins/genetics* ; Face/abnormalities* ; Female ; Hematologic Diseases ; Humans ; Infant ; Neoplasm Proteins/genetics* ; Phenotype ; Vestibular Diseases

OBJECTIVE: To explore the genetic basis for a child featuring complex cortical dysplasia and other brain malformations (CDCBM3). METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out for the family trio. Suspected variant was verified by Sanger sequencing. RESULTS: The proband, a 1-year-and-2-month old Chinese boy, had presented with motor developmental delay, lissencephaly, severe cognitive impairments, absent speech and congenital laryngomalacia. WES revealed that he has harbored a heterozygous missense variant of the KIF2A gene, namely NM_001098511.2: c.952G>A, p.Gly318Arg (GRCh37/hg19). The highly conserved residue is located around the ATP nucleotide-binding pocket in the kinesin motor domain (PM1). The variant was not found in the Genome Aggregation Database and the 1000 Genomes Project (PM2), and was predicted to be deleterious on the gene product by multiple in silico prediction tools (PP3). This variant was unreported previously and was de novo in origin (PS2). Based on the ACMG guidelines, it was categorized as likely pathogenic (PS2+PM1+PM2+PP3). Furthermore, the congenital laryngomalacia found in our patient was absent in previously reported CDCBM3 cases. CONCLUSION The novel variant of the KIF2A gene probably underlay the disorders in the proband. Above finding has expanded the phenotypic and mutational spectrum of CDCBM3.
Asians/genetics* ; Brain ; China ; Humans ; Infant ; Kinesins/genetics* ; Male ; Malformations of Cortical Development/genetics* ; Whole Exome Sequencing

OBJECTIVE: To explore the genotype-phenotype correlation of a case with GM1-gangliosidosis caused by compound heterogenic variants in GLB1. METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Trio-based whole-exome sequencing (WES) was performed for the family and suspected mutation was verified by Sanger sequencing. RESULTS: The proband, a 2-year-3-month old Chinese girl, presented with psychomotor deterioration, absent speech, intellectual disabilities and behavior problem. Trio-based WES has identified compound heterozygosity for 2 variants in the GLB1 gene: NM_000404.2:c.1343A>T, p.Asp448Val and c.1064A>C, p.Gln355Pro (GRCh37/hg19),which was inherited from the mother and father, respectively. Homozygous or compound heterozygous pathogenic variants in GLB1, encoding β-galactosidase, are responsible for GM1-gangliosidosis,an autosomal recessive lysosomal storage disorder characterized by variable degrees of neurodegeneration and skeletal abnormalities. The p.Asp448Val variant has been classified as pathogenic for GM1 gangliosidosis in medical literatures for the reason that functional studies demonstrated that expression of the p.Asp448Val variant in COS-1 cells resulted in no detectable β-galactosidase activity compared to wild type GLB1. The p.Gln355Pro variant has not been reported in literatures or database. The variant is highly conserved residue (PM1), and was not found in either the Genome Aggregation Database or the 1000 Genomes Project (PM2) and was predicted to have a deleterious effect on the gene product by multiple in silico prediction tools (PP3). Next, the β-galactosidase activity of the patient's peripheral blood leukocytes was determined by fluorescent method. The result was 0.0 nmol/mg. It showed that the p.Gln355Pro variant also resulted in loss of β-galactosidase activity, thus the variant was classified into clinical pathogenic variant. CONCLUSION Our study expands the mutational spectrum of the GLB1 gene and provides genetic counseling for the family.
Asians/genetics* ; China ; Female ; G(M1) Ganglioside ; Gangliosidosis, GM1/genetics* ; Humans ; Mutation ; beta-Galactosidase/genetics*