ASSOCIATION BETWEEN POLYMORPHISM IN THE PROMOTER REGION (G/C-915) OF PAX9 GENE AND THIRD MOLAR AGENESIS

Purpose:

Hypodontia is the congenital absence of one or more (up to six) permanent and/or deciduous teeth, being one of the most common alterations of the human dentition. Genetic polymorphisms are variations of DNA sequences occurring in a population. This study investigated whether G-915C single nucleotide polymorphism (SNPs) in the PAX9 gene promoter is associated with hypodontia in humans.

Material and Methods:

The polymorphism in region G/C-915 of PAX9 gene (NCBI ref SNP ID: rs 2073247) of 240 patients was analyzed, being 110 controls and 130 individuals with third molar agenesis. After DNA extraction, the region of interest was amplified by PCR technique using two different primers. The significance of the differences in observed frequencies of polymorphisms in both groups was assessed by odds-ratio and chi-squared test with 95% confidence interval.

Results:

Genotype CC was more frequent in patients with agenesis (11.5%) compared to the control (1.8%), while GG was more prevalent in the control group (39.1%) compared to the individuals with agenesis (26.2%).

Conclusion:

These data showed that the allele C could be associated with the third molar agenesis.     

Noggin inhibition of mouse dentinogenesis

ObjectivesThe Bone Morphogenetic Proteins (BMPs) direct tooth development and still express in the adult tooth. We hypothesized that inhibition of BMP function would therefore disrupt dentinogenesis by differentiated odontoblasts.MethodsWe generated mice overexpressing the BMP-inhibitory protein Noggin in differentiated odontoblasts and osteocytes under control of a Dmp1 promoter-driven cre transgene. We compared the dentin phenotype in these mice with that in WT littermates and in mice with a Smad4 odontoblast/osteocyte knockout mediated by the same cre and therefore lacking all BMP and Tgfβ signaling in the same tissues.ResultsThree-month-old first molars from both Noggin-expressing and Smad4-deleted mice showed decreased dentin volume with enlarged pulp cavities, and both displayed less organized and mineralized dentinal tubules compared to WT. The Smad4-ablated phenotype was more severe. While dentin sialophosphoprotein (DSPP) and bone sialoprotein (BSP) were decreased in the dentin of both lines, dentin matrix protein 1 (DMP1) was sharply increased in Noggin-expressing teeth.ConclusionsThe phenotypes we observed in Noggin-overexpressing and Smad4-conditional knockout teeth resemble the phenotype of Dentinogenesis Imperfecta (DGI) type III. Our results show that BMPs regulate post-natal dentinogenesis and that BMP-inhibitory proteins like Noggin play a role in that regulation. The increased severity of the Smad4 phenotype indicates that Tgfβ ligands, in addition to BMPs, play a crucial role in post-developmental dentinogenesis.     

160 kb deletion in ISPD unmasking a recessive mutation in a patient with Walker–Warburg syndrome

Walker–Warburg syndrome (WWS) is a severe muscular dystrophy with eye and brain malformations. On a molecular level, WWS is a disorder of the O-linked glycosylation of α-dystroglycan and therefore referred to as one of the dystroglycanopathies. The disease family of muscular dystrophy–dystroglycanopathy (MDDG) contains a spectrum of severe to mild disorders, designated as MDDG type A to C. WWS, as the most severe manifestation, corresponds to MDDG type A. Defects in the genes POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, GTDC2, G3GALNT2, GMPPB, B3GNT1, TMEM5 and COL4A1 and ISPD have been described as causal for several types of MDDG including WWS, but can only be confirmed in about 60–70% of the clinically diagnosed individuals. The proteins encoded by these genes are involved in the posttranslational modification of α-dystroglycan. Mutations in POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, GMPPB, TMEM5 and COL4A1 and ISPD lead to a wide spectrum of phenotypes of congenital muscular dystrophies with or without eye and brain abnormalities. Patients with WWS frequently demonstrate a complete lack of psychomotor development, severe eye malformations, cobblestone lissencephaly and a hypoplastic cerebellum and brainstem, seizures, hydrocephalus and poor prognosis. Here, we present a boy with WWS who showed compound heterozygous changes in ISPD and discuss the clinical and radiological phenotype and the molecular genetic findings, including a novel pathogenic mutation in ISPD.     

老年人拔牙情况及术后出血原因分析与护理

目的:分析老年人拔牙情况及拔牙术后出血原因,探讨护理方法。方法:回顾性分析112例老年人拔牙原因、出血时间、出血原因等临床因素,总结护理方法。结果:老年人拔牙的主要原因是牙周病松动牙、残根、修复需要和创伤后拔牙,大部分出血发生于牙拔除12 h内,通过局部和全身对症处理均得到有效止血。结论:局部及全身因素均可造成拔牙术后出血,术前详细询问病史,运用微创拔牙术,采取相应的护理措施可减少拔牙术后出血。     

Gonadal agenesis with hypoplastic paramesonephric ducts (PMNDs) derivatives in dizygotic twins

The co-occurrence of gonadal agenesis alongside hypoplastic derivatives of the paramesonephric ducts has rarely been observed. Patient(s): 16-year-old dizygotic twin sisters were referred to our department because of primary amenorrhea. X-ray, bone densitometry, ultrasonography, pelvic MRI and measurement of pituitary, ovary, and thyroid hormones were performed. Both twins showed hypergonadotropic hypogonadism, bilateral gonadal agenesis, fallopian tube, uterus, and vaginal hypoplasia but normal kidney and urinary tract structures and skeletal system. Analysis of Q-banded chromosomes in peripheral blood for the search for centromeric X-chromosome DNA and SRY gene was normal as well as the molecular analysis of FMR1, GDF9, and BMP15 genes. Estradiol gel was administered for one year followed by estroprogestin treatment. Both twins growth increased; breast development was stimulated and first menses occurred. Deregulation in the expression of the various HOX genes along the axis of the developing reproductive tract in a determinate time of development may be one of the mechanisms involved in the origin of this complex and rare association.     

Partial Cervical Agenesis and Complete Vaginal Atresia

BackgroundThe objective of this study was to report 2 cases of the combined congenital anomalies of complete vaginal atresia and partial cervical agenesis, and highlight the limitations of magnetic resonance imaging for definitive initial diagnosis, and consequently the importance of early definitive management, to avoid life-threatening sepsis. Herein we provide a retrospective case audit of two patients with congenital abnormalities between 2005 and 2013 who were treated in a quaternary statewide pediatric and adolescent gynecology center.CasesTwo patients with the combined congenital anomalies of complete vaginal agenesis and partial cervical agenesis highlight the difficulties encountered with the limitations of magnetic resonance imaging in accuracy of diagnosis, as well as development of life-threatening sepsis that requires hysterectomy. Both patients were initially imaged as having distended endometrial cavities and cervical canals with what was thought to be an obstructive upper vaginal septum and absent lower vagina. Both required initial neovagina creation, however the cervices were never clinically or surgically visualized.Summary and ConclusionPartial cervical agenesis is a relatively rare form of Müllerian abnormality which, if not diagnosed and definitively treated early, can have significant morbidity and mortality. Although magnetic resonance imaging is the diagnostic imaging gold standard for Müllerian abnormalities, it is important to recognize the limitations of this modality, the potential sequelae of these limitations, and to appreciate the importance of early accurate diagnosis and treatment of this condition. Importantly, if the imaging diagnosis does not completely correlate with the clinical and surgical findings, then a high suspicion of complete or partial cervical agenesis is prudent, because the consequences of nondefinitive early treatment can be life-threatening and potentially fatal.     

Improved testing for CMT1A and HNPP using multiplex ligation-dependent probe amplification (MLPA) with rapid DNA preparations: comparison with the interphase FISH method

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are the two most common peripheral neuropathies, with incidences of about 1 in 2,500. Several techniques can be used to detect the typical 1.5-Mb duplication or deletion associated with these respective conditions, but none combines simplicity with high sensitivity. MLPA is a new technique for measuring sequence dosage. We have assessed its performance for the detection of the specific 1.5-Mb duplication/deletion by prospectively testing 50 patients referred with differential diagnoses of CMT or HNPP. Probes were designed to evaluate the TEKT3, PMP22, and COX10 genes within the CMT1A/HNPP region. We have compared the results with our existing fluorescence in situ hybridization (FISH) assay, which was performed in parallel. There was concordance of results for 49 patients. Of note, one patient showed an intermediate multiplex ligation-dependent probe amplification (MLPA) result with an abnormal FISH result, which is consistent with mosaicism. The assay works equally well with either purified DNA or rapid DNA preparations made by direct cell lysis. The use of the latter significantly reduces the cost of the assay. MLPA is a sensitive, specific, robust, and cost-effective technique suitable for fast, high-throughput testing and offers distinct advantages over other testing methods.