Expanding the spectrum of PTH1R mutations in patients with primary failure of tooth eruption

Objectives

Primary failure of tooth eruption (PFE) is a rare autosomal-dominant disease characterized by severe lateral open bite as a consequence of incomplete eruption of posterior teeth. Heterozygous mutations in the parathyroid hormone 1 receptor (PTH1R) gene have been shown to cause PFE likely due to protein haploinsufficiency. To further expand on the mutational spectrum of PFE-associated mutations, we report here on the sequencing results of the PTH1R gene in 70 index PFE cases.

Materials and methods

Sanger sequencing of the PTH1R coding exons and their immediate flanking intronic sequences was performed with DNA samples from 70 index PFE cases.

Results

We identified a total of 30 unique variants, of which 12 were classified as pathogenic based on their deleterious consequences on PTH1R protein while 16 changes were characterized as unclassified variants with as yet unknown effects on disease pathology. The remaining two variants represent common polymorphisms.

Conclusions

Our data significantly increase the number of presently known unique PFE-causing PTH1R mutations and provide a series of variants with unclear pathogenicity which will require further in vitro assaying to determine their effects on protein structure and function.

Clinical relevance

Management of PTH1R-associated PFE is problematic, in particular when teeth are exposed to orthodontic force. Therefore, upon clinical suspicion of PFE, molecular DNA testing is indicated to support decision making for further treatment options.     

异落新妇甙的结构研究

从百合科菝葵属植物土茯苓(Smilaxg labra Roxb.)根茎的乙醇提取物中分得一个新的天然化合物(I),命名为异落新妇甙(isoastilbin)。根据元素分析,UV,IR,¹H-NMR,¹³C-NMR,2DNMR及FAB-MS,确定化合物I的结构为5,7,3',5'-四羟基二氢黄酮醇-3-O-α-L-鼠李糖甙。     

Bioactive asterosaponins from the starfish Culcita novaeguineae

Two new sulfated steroidal pentaglycosides（asterosaponins）,novaeguinosides Ⅰ（2） and （Ⅱ）2,along with the known regularoside B（1）were isolated from the starfish Culcita novaeguineae.Their structures were elucidated by extensive NMR techniques as well as chemical evidence.     

Klinik und Differentialdiagnose der cranialen Migrationshemmung des Rückenmarks

Zusammenfassung Nach einer Literatur-und pathomorphologischen Übersicht wird an Hand von 23 Fällen einer spinalen Malformation unterschiedlicher Genese das klinische Bild der cranialen Migrationshemmung herausgearbeitet. Für die Diagnose ist neben Hautveränderungen über der dorsalen Mittellinie, wie sie für den dysrhaphischen Formenkreis typisch sind, die neurologische Symptomatik der unteren Extremitäten richtungweisen. Der Beweis einer Aszensionshemmung kann nur durch die Myelographie erbracht werden. Die Bedeutung frühzeitiger operativer Maßnahmen zur Verhinderung progredienter Ausfälle wird besonders herausgestellt.

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Clinical features and differential diagnosis of the restricted cranial migration of the spinal cord

After a review of the literature on, and the pathology of spinal malformations the clinical features of a restricted ascent of the spinal cord are described with reference to 23 cases of spinal dysrhaphism of varying genesis. The suppression of cranial migration is caused either by a diastematomyelia, a lipoma, or a dermoid sinus with direct connection to the spinal cord, or else by myelomeningoceles and cicatrices after arachnitis.The symptoms occur particularly during the early years of life and in the age group of between 20 and 30.The manifestations of the disease are changes over the dorsal midline which are typical for spinal dysraphism, neurological defects of the lower limbs, and abnormalities in the function of bladder and rectum. Deformations of the feet and trophic disturbances have been encountered.Important for the diagnosis is a radiographic investigation of the spine since a restriction of the cranial migration can only be proved by myelography. Operation with view of a release of the spinal cord is the method of choice. The importance of early operative measures for the prevention of progredient deficiencies is particularly stressed.

     

A bronchogenic cyst of the right ventricular endocardium

In a 73-year-old male patient with a history of prostate cancer, a right ventricular endoluminal tumor was diagnosed by echocardiography. An endocardial papillary fibroelastoma or myxoma appeared possible; a malignant tumor could not be ruled out. The tumor was resected using extracorporeal circulation and cardioplegic arrest. Histopathology study revealed a bronchogenic cyst with ciliated epithelium.