OBJECTIVE: To explore the genetic bases of 3 patients with periventricular nodular heterotopia and epileptic seizure. METHODS: The clinical data of three patients presenting with periventricular nodular ectopic with epileptic seizure were analyzed. Whole exome sequencing (WES) was performed on the patients, and Sanger sequencing was used to validate the suspected variants. RESULTS: In three female patients, head MRI showed nodular gray matter ectopic in the bilateral ventricle. WES identified the heterozygous c.2720del T(p.Leu907Argfs*39) variant of FLNA gene in case 1 and her mother (case 2), and heterozygous c.1387_1390del GTGC(p.Val463Profs*34) of FLNA gene in case 3. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC (p.Val463Profs*34) variants of FLNA gene were predicted to be pathogenic (PVS1+PM2+PP1) and likely pathogenic(PVS1+PM2), respectively. CONCLUSION The c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC(p.Val463Profs*34) variants of FLNA gene may be the genetic cause of the three patients.
Epilepsy/genetics* ; Female ; Filamins/genetics* ; Heterozygote ; Humans ; Magnetic Resonance Imaging ; Mutation ; Periventricular Nodular Heterotopia/genetics* ; Seizures

OBJECTIVE: To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure. METHODS: Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations. CONCLUSION Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.
Abnormalities, Multiple/genetics* ; Bone Diseases, Developmental/genetics* ; Epilepsy/genetics* ; Facies ; Humans ; Intellectual Disability/genetics* ; Phenotype ; Repressor Proteins/genetics* ; Seizures/genetics* ; Tooth Abnormalities/genetics*

Objective To explore the expression and significance of serum DKK1 in patients with gastric cancer. Methods We selected 170 gastric cancer patients (gastric cancer group) and 170 subjects with non-gastric cancer during the same period (control group). ELISA was used to detect the DKK1 level. The ROC curve was used to evaluate the diagnostic performance, and we analyzed the relation between DKK1 level and age, gender, family history of gastric cancer, cigarette smoking, alcohol consumption, tumor size, TNM stage, infiltration depth, lymph node metastasis, liver metastasis, vascular invasion, perineural invasion. Results The serum DDK1 level in GC patients was higher than that in control group (P < 0.0001). ROC curve showed that the possible optimal cut-off value of DKK1 for gastric cancer patients was 167.8 pg/ml, AUC was 0.908, sensitivity was 80.59%, and specificity was 84.71%. There was no significant relation between the serum DKK1 level and age, gender, family history of gastric cancer, cigarette smoking, alcohol consumption, tumor size, liver metastasis, vascular invasion or distant metastasis (all P > 0.05). However, DKK1 level was significantly related with TNM stage, infiltration depth, lymph node metastasis and perineural invasion (all P < 0.05). Conclusion Serum DKK1 level is higher in gastric cancer patients than that of control group and related with the severity of lesions, which indicates that serum DKK1 may be a potential biomarker for gastric cancer screening.