OBJECTIVETo investigate the proliferative potential of the epithelial cells in odontogenic keratocyst, radicular cyst, dentigerous cyst and ameloblastoma.

METHODSDNA contents and ploidy of basal and spinous cells in keratocyst, radicular cyst, dentigerous cyst, and the peripheral column cells and central reticular cells in ameloblastoma were analysis respectively.

RESULTSThe more and higher DNA contents and the proliferating ploidy of keratocyst and ameloblastoma than those of radicular cyst and dentigerous cyst indicate the active proliferating potential. The spinous cells showed more active proliferating growth than the basal cells of keratocyst. The higher DNA contents of radicular cyst are related to the stimulus of the inflammation. The dentigerous cysts have more di-ploidy cells without active growth potential.

CONCLUSIONSThe active cell proliferating growth in keratocyst and ameloblastoma is probably the pathological basis of their local aggressive biological behavior.

Ameloblastoma ; genetics ; pathology ; Cell Division ; genetics ; DNA ; metabolism ; Humans ; Jaw Neoplasms ; genetics ; pathology ; Odontogenic Cysts ; genetics ; pathology ; Ploidies

Objective: To detect the SMO mutations in odontogenic keratocyst (OKC) and to explore the mechanism behind. Methods: Patients with OKC who received treatment in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology,Peking University, from September 2012 to June 2017 were enrolled. OKC samples from 10 patients diagnosed as naevoid basal cell carcinoma syndrome (NBCCS)-related OKC (4 females and 6 males) and 20 patients diagnosed as sporadic OKC (7 females and 13 males) were collected. Genomic DNAs were extracted from fibrous capsules and epithelial lining respectively. SMO mutations were detected and analyzed by Sanger sequencing. Results: Three SMO mutations were found in one NBCCS-associated OKC who carrying c.2081C>G (p.P694R) mutation) and two sporadic OKC who carrying c.907C>T (p.L303F) mutation and c.1247_1248delinsAA (p.G416E), respectively), among which the first two mutations were novel mutations that had not been reported before. Besides, two mutations in sporadic OKC were not paired with PTCH1 mutations. Conclusions: In addition to PTCH1 gene mutations, SMO gene mutations also exist in OKC which might be related to the development of OKC.
Basal Cell Nevus Syndrome/genetics* ; Female ; Humans ; Male ; Mutation ; Odontogenic Cysts/genetics* ; Odontogenic Tumors/genetics* ; Smoothened Receptor/genetics*

OBJECTIVETo detect potential mutation of MLC1 gene in a child affected with megalencephalic leukoencephalopathy with subcortical cysts (MLC).

METHODSClinical symptoms of the patient were retrieved. Peripheral blood DNA samples from the patient, her parents and healthy controls were collected. Potential mutation of the MLC1 gene was detected by polymerase chain reaction and Sanger sequencing.

RESULTSThe patient presented with severe motor developmental delay and a giant skull. Magnetic resonance scan showed diffuse white matter swelling in bilateral hemispheres. DNA sequencing identified a novel homozygous c.177-c.180delC mutation of the MLC1 gene. The parents of the patient both carried a heterozygous mutation c.177-c.180delC but had a normal phenotype.

CONCLUSIONA novel MLC1 mutation c.177-c.180delC has been identified in a patient with MLC. The mutation is presumably disease-causing and has derived from parents who are both carriers.

Child, Preschool ; Cysts ; genetics ; Female ; Hereditary Central Nervous System Demyelinating Diseases ; genetics ; Humans ; Membrane Proteins ; genetics ; Mutation

Hirschsprung's disease is one of the most common causes of intestinal obstruction in neonates and infants. The underlying pathology of this disease is the absence of the ganglion cells in both the myenteric (Auerbach's) plexus and the submucosal (Meissner's) plexus. Since Hirschsprung's report in 1886, there have been thousands of papers on Hirschsprung's disease but the cause of the absence of the ganglion cells has not been identified. Hirschsprung's disease can be successfully treated with the Swenson, the Duhamel, and the Soave operations even though the pathogenesis is unknown. With the recent progress of molecular biology and genetics, a more detailed approach to the pathogenesis of Hirschsprung's disease can be undertaken. In addition, there have been recent developments in the surgical approach. In this review, recent advances in surgery for Hirschsprung's disease are presented.
Ganglion Cysts ; Genetics ; Hirschsprung Disease* ; Humans ; Infant ; Infant, Newborn ; Intestinal Obstruction ; Molecular Biology ; Pathology

OBJECTIVE: This study aimed to investigate the clinical phenotype and genetic characteristics of Chinese families with Van der Woude syndrome (VWS). METHODS: Clinical manifestations between 14 families and within each family were recorded. Possible inheritance modes and pathogenic genes were analyzed. Phenotypic distribution and gene frequencies were calculated. RESULTS: Of the pedigrees investigated, an autosomal dominant inheritance pattern was suggested. All patients had typical symptoms. The pathogenic gene was interferon regulatory factor 6 (IRF6). Phenotypic distribution frequencies were as follows: lip pits (91.9%), cleft lip and/or palate (73.0%), and hyperdontia (8.1%). There were significant differences in clinical phenotypes among individuals of different families and individuals of the same family. CONCLUSIONS VWS in a Chinese population was dominantly inherited with high penetrance and variable expressivity. The pathogenic gene was IRF6. VWS in a Chinese population was genotyped as VWS1.
Abnormalities, Multiple ; genetics ; Cleft Lip ; genetics ; Cleft Palate ; genetics ; Cysts ; genetics ; Humans ; Interferon Regulatory Factors ; genetics ; Lip ; abnormalities ; Mutation ; Pedigree ; Syndrome

The clinical data of a patient with megalencephalic leukoencephalopathy (MLC) with subcortical cysts and her parents were collected. MLC1 gene mutation was detected by polymerase chain reaction and direct DNA sequencing. The patient presented with motor developmental delay and giant skull, and brain magnetic resonance imaging showed diffuse white matter swelling accompanied by subcortical cysts in bilateral frontal and parietal lobes. Gene sequencing identified two heterozygous mutations of MLC1, including missense mutation in exon 3 (c.217G>A, p.Gly73Arg) and splice site mutation in intron 9 (c.772-1G>C in IVS9-1). The patient's parents both had heterozygous mutation c.772-1G>C in IVS9-1 with normal phenotype. It can be presumed that c.772-1G>C in IVS9-1 comes from the parents, and c.217G>A (p.Gly73Arg) is a de novo mutation.
Asian Continental Ancestry Group ; genetics ; Cysts ; genetics ; Female ; Hereditary Central Nervous System Demyelinating Diseases ; genetics ; Humans ; Infant ; Membrane Proteins ; genetics ; Mutation

OBJECTIVE: To explore the clinical features and genetic variant in a child featuring megalencephalic leukoencephalopathy with subcortical cyst (MLC) type 2B. METHODS: Clinical and imaging data of the child was collected. Potential variant of hepatocyte adhesion molecule (HEPACAM) gene was detected by Sanger sequencing. The growth and development of her mother and uncle was also reviewed. RESULTS: The patient, a 1-year-and-7-month female, presented with convulsion, mental retardation and abnormally increased head circumference. Cranial MRI revealed extensive long T1 long T2 signals in the white matter of bilateral cerebral hemisphere, right anterior sac cyst, cerebral gyrus widening, and shallow sulcus. Sanger sequencing identified a c.437C>T missense variant in exon 3 of the HEPACAM gene. The same variant was detected in her mother but not father. Her mother and maternal uncle both had a history of increased head circumference when they were young. In their adulthood, the head circumference was in the normal range but still greater than the average. CONCLUSION The heterozygous variant of the HEPACAM gene probably underlies the MLC2B in this child. The variant has derived from her asymptomatic mother, which suggested incomplete penetrance of the MLC2B.
Adult ; Cell Cycle Proteins ; genetics ; Cerebrum ; diagnostic imaging ; Cysts ; diagnostic imaging ; genetics ; Female ; Genetic Variation ; Hereditary Central Nervous System Demyelinating Diseases ; diagnostic imaging ; genetics ; Humans ; Infant

Odontogenic keratocysts (OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome (NBCCS). OKCs are locally aggressive, cause marked destruction of the jaw bones and have a propensity to recur. PTCH1 mutations (at ∼80%) are frequently detected in the epithelia of both NBCCS-related and sporadic OKCs, suggesting that PTCH1 inactivation might constitutively activate sonic hedgehog (SHH) signalling and play a major role in disease pathogenesis. Thus, small molecule inhibitors of SHH signalling might represent a new treatment strategy for OKCs. However, studies on the molecular mechanisms associated with OKCs have been hampered by limited epithelial cell yields during OKC explant culture. Here, we constructed an isogenic PTCH1 cellular model of PTCH1 inactivation by introducing a heterozygous mutation, namely, c.403C>T (p.R135X), which has been identified in OKC patients, into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. This was followed by the induction of epithelial differentiation. Using this in vitro isogenic cellular model, we verified that the PTCH1 heterozygous mutation causes ligand-independent activation of SHH signalling due to PTCH1 haploinsufficiency. This activation was found to be downregulated in a dose-dependent manner by the SHH pathway inhibitor GDC-0449. In addition, through inhibition of activated SHH signalling, the enhanced proliferation observed in these induced cells was suppressed, suggesting that GDC-0449 might represent an effective inhibitor of the SHH pathway for use during OKC treatment.
Anilides ; pharmacology ; Basal Cell Nevus Syndrome ; Hedgehog Proteins ; genetics ; pharmacology ; Humans ; Molecular Targeted Therapy ; Odontogenic Cysts ; genetics ; physiopathology ; therapy ; Odontogenic Tumors ; genetics ; physiopathology ; therapy ; Pyridines ; pharmacology

OBJECTIVETo study hTERT mRNA expression in ameloblastoma (AB) and odontogenic keratocyst (OKC) and to investigate genesis, development and biological characteristics of AB and OKC.

METHODShTERT mRNA expression in 54 cases of AB, 16 cases of OKC, 7 cases of oral normal mucosa was detected by in situ hybridization.

RESULTSThe positive rates of hTERT mRNA in AB, OKC, and oral normal mucosa were 94.4% (51/54), 87.5% (14/16), 1/7, respectively. There was significant statistical difference (P < 0.001). About clinicalpathology of AB, there was no difference for hTERT expression (P > 0.05) hTERT mRNA was positive in peripheral and stellate reticula cells.

CONCLUSIONS(1) hTERT activity plays an important role in genesis, development of AB. (2) hTERT positive rate is related to cell differentiation and clinical biological behavior.

Ameloblastoma ; DNA-Binding Proteins ; metabolism ; Humans ; Jaw Neoplasms ; Odontogenic Cysts ; Odontogenic Tumors ; metabolism ; RNA, Messenger ; metabolism ; Telomerase ; genetics

Genetic polymorphisms of encoding antigen B2 gene (AgB2) in Echinococcus granulosus were studied using PCR-RFLP and DNA sequencing among 20 Egyptian isolates. Five isolates from different host origins (humans, camels, pigs, and sheep) were collected and used. All examined isolates of each host group gave very similar patterns of PCR-RFLP after restriction enzyme digestion with AluI, with the gene size of approximately 140 bp and 240 bp for sheep and human isolates, and approximately 150 bp and 250 bp for pig and camel isolates. No digestion pattern was obtained after incubation of all studied isolates with EcoRI. These results reveal high intra-group homogeneity. DNA sequence analysis highlighted that human infecting strain showed 100% identity with respect to sheep infecting isolate, 96% and 99% with pig and camel infecting isolates, respectively.
Animals ; Camels ; Cysts/parasitology ; Echinococcosis/*parasitology/*veterinary ; Echinococcus granulosus/*genetics/isolation & purification ; *Genetic Variation ; Humans ; Lipoproteins/*genetics ; Parasitic Diseases, Animal/*parasitology ; Sheep