Connector design effects on the in vitro fracture resistance of 3-unit monolithic prostheses produced from 4 CAD-CAM materials.

STATEMENT OF PROBLEM: Studies that compared the fracture strength of monolithic lithium disilicate and 5-mol% yttria partially stabilized zirconia multiunit fixed dental prostheses are sparse. PURPOSE: As the connector is the weakest part of a fixed dental prosthesis, the purpose of this in vitro study was to investigate the effect of connector designs and material on the fracture strength of 3-unit monolithic fixed dental prostheses. MATERIAL AND METHODS: Resin-ceramic canine and premolar teeth (N=144) were prepared for fixed dental prosthesis abutments. Prostheses with 3 connector designs (width=height, widthheight) were made from 2 types of lithium disilicate (IPS e.max CAD and Amber Mill) and 5-mol% yttria partially stabilized zirconia (3M Lava Esthetic and Katana Zirconia UTML). Fracture strengths were measured after 200 000 cycles of dynamic loading of 50 N and thermocycling at 5 °C and 55 °C, and the fracture patterns were analyzed. Two-way analysis of variance and the Fisher exact test were used for statistical analysis (α=.05). RESULTS: The material and connector design affected the fracture strength of fixed dental prostheses (P<.05), and a significant interaction was found between the material and connector design (P<.05). The IPS e.max CAD material had significantly lower fracture strength than Amber Mill, 3M Lava Esthetic, or Katana Zirconia UTML (P<.05). Connector designs with a greater width versus height showed significantly lower fracture strengths than other designs (P<.05). CONCLUSIONS: The connector design of 3-unit fixed dental prostheses, particularly the connector height, may affect fracture strength depending on the prosthesis material.

Severe phenotypes in a Charcot-Marie-Tooth 1A patient with PMP22 triplication.

Charcot-Marie-Tooth disease (CMT) is a genetically and clinically heterogeneous hereditary motor and sensory neuropathy signified by a distal symmetric polyneuropathy. The most frequent subtype is type 1A (CMT1A) caused by duplication in chromosome 17p12 that includes PMP22. This study reports a woman with a family history of CMT1A due to PMP22 duplication. However, she presented with a more severe phenotype than her sibling or ancestors and was found to have a PMP22 triplication instead of the duplication. This was caused by de novo mutation on her affected mother's duplication chromosome. Her lower limb magnetic resonance imaging revealed severe diffused atrophy and fatty replacement. However, her affected sister with typical PMP22 duplication showed almost intact lower limb. Triplication patient's median motor nerve conduction velocity was far lower compared with her sister. Her onset age was faster (8 years) than her sister (42 years). CMT1A triplication might be generated by a female-specific chromosomal rearrangement mechanism that is different from the frequent paternal-originated CMT1A duplication. It also suggests that the wide phenotypic variation of CMT1A might be partly caused by unstable genomic rearrangement, including PMP22 triplication.

A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy.

BACKGROUND: Mutations in MPV17 cause the autosomal recessive disorder mitochondrial DNA depletion syndrome 6 (MTDPS6), also called Navajo neurohepatopathy (NNH). Clinical features of MTDPS6 is infantile onset of progressive liver failure with seldom development of progressive neurologic involvement. METHODS: Whole exome sequencing (WES) was performed to isolate the causative gene of two unrelated neuropathy patients (9 and 13 years of age) with onset of the syndrome. Clinical assessments and biochemical analysis were performed. RESULTS: A novel homozygous mutation (p.R41Q) in MPV17 was found by WES in both patients. Both showed axonal sensorimotor polyneuropathy without liver and brain involvement, which is neurophysiologically similar to axonal Charcot-Marie-Tooth disease (CMT). A distal sural nerve biopsy showed an almost complete loss of the large and medium-sized myelinated fibers compatible with axonal neuropathy. An in vitro assay using mouse motor neuronal cells demonstrated that the abrogation of MPV17 significantly affected cell integrity. In addition, the expression of the mutant protein affected cell proliferation. These results imply that both the loss of normal function of MPV17 and the gain of detrimental effects of the mutant protein might affect neuronal function. CONCLUSION: We report a novel homozygous mutation in MPV17 from two unrelated patients harboring axonal sensorimotor polyneuropathy without hepatoencephalopathy. This report expands the clinical spectrum of diseases caused by mutations of MPV17, and we recommend MPV17 gene screening for axonal peripheral neuropathies.

Initial Change in the Occlusal Force and Occlusal Contact Area Following Single Molar Implant Restoration.

PURPOSE: The occlusal force and occlusal contact area may be used to evaluate oral function following restoration of a missing tooth. This study aimed to monitor the initial changes in these factors after single molar implant restoration. MATERIALS AND METHODS: Patients who underwent single implant restoration between December 2018 and September 2019 were recruited for this study. Occlusal force was measured before, immediately after, and 1 month after prosthesis placement. The occlusal contact area was evaluated immediately and 1 month after the placement. Data were grouped by sex, restored tooth, and restored side for analysis. RESULTS: In most groups, occlusal force was significantly increased 1 month after the placement compared with that before placement (P < .05), and the change was more significant in the first molar group than in the second molar group. There was a significant difference in the occlusal contact area of the implant prosthesis immediately and 1 month after placement when a thickness of 9 µm was used. The occlusal contact area of the natural tooth in the mesial side was significantly increased 1 month after placement (P < .05). CONCLUSION: Occlusal force was significantly increased 1 month after implant restoration, and restoration of the first molar had the most significant effect on the occlusal force. Occlusal contact areas may differ according to the occlusal indicator used in the clinical setting because the changes were significant with only 0 to 9 µm.

A novel Lys141Thr mutation in small heat shock protein 22 (HSPB8) gene in Charcot-Marie-Tooth disease type 2L.

Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous peripheral neuropathies. HSPB8 gene encodes heat shock protein 22 (HSP22) which belongs to the superfamily of small stress induced proteins. Mutations in HSPB8 are implicated to CMT2L and distal hereditary motor neuropathy 2A (dHMN2A). All three reported HSPB8 mutations are interestingly located in the Lys141 residue. In the present study, we examined a Korean axonal CMT patient who presented distal limb atrophy, sensory loss, areflexia, and axonal loss of large myelinated fibers. Whole exome sequencing identified a novel missense mutation c.422A>C (p.Lys141Thr) in HSPB8 as the underlying cause of the CMT2 patient. The mutation was regarded as a de novo case because both unaffected parents have no such mutation. The patient with HSPB8 mutation is the first case in Koreans. Clinical heterogeneities have been revealed in patients with Lys141 mutation; the present patient revealed similar phenotype of CMT2L. In addition, the lower limb MRI revealed a similarity between our HSPB8 and HSPB1 patients. It seems that the Lys141 site in the alpha-crystallin domain of HSPB8 is regarded as a mutational hot spot for peripheral neuropathy development, and mutations even in the same codon can exhibit different CMT phenotypes.

Exome Sequencing Reveals a Novel PRPS1 Mutation in a Family with CMTX5 without Optic Atrophy.

BACKGROUND: X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is caused by mutations in the gene encoding phosphoribosyl pyrophosphate synthetase I (PRPS1). There has been only one case report of CMTX5 patients. The aim of this study was to identify the causative gene in a family with CMTX with peripheral neuropathy and deafness. CASE REPORT: A Korean family with X-linked recessive CMT was enrolled. The age at the onset of hearing loss of the male proband was 5 months, and that of steppage gait was 6 years; he underwent cochlear surgery at the age of 12 years. In contrast to what was reported for the first patients with CMTX5, this patient did not exhibit optic atrophy. Furthermore, there was no cognitive impairment, respiratory dysfunction, or visual disturbance. Assessment of his family history revealed two male relatives with very similar clinical manifestations. Electrophysiological evaluations disclosed sensorineural hearing loss and peripheral neuropathy. Whole-exome sequencing identified a novel p.Ala121Gly (c.362C>G) PRPS1 mutation as the underlying genetic cause of the clinical phenotype. CONCLUSIONS: A novel mutation of PRPS1 was identified in a CMTX5 family in which the proband had a phenotype of peripheral neuropathy with early-onset hearing loss, but no optic atrophy. The findings of this study will expand the clinical spectrum of X-linked recessive CMT and will be useful for the molecular diagnosis of clinically heterogeneous peripheral neuropathies.

Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease.

BACKGROUND: Mutations in the Pleckstrin homology domain-containing, family G member 5 (PLEKHG5) gene has been reported in a family harboring an autosomal recessive lower motor neuron disease (LMND). However, the PLEKHG5 mutation has not been described to cause Charcot-Marie-Tooth disease (CMT). METHODS: To identify the causative mutation in an autosomal recessive intermediate CMT (RI-CMT) family with childhood onset, whole exome sequencing (WES), histopathology, and lower leg MRIs were performed. Expression and activity of each mutant protein were analyzed. RESULTS: We identified novel compound heterozygous (p.Thr663Met and p.Gly820Arg) mutations in the PLEKHG5 gene in the present family. The patient revealed clinical manifestations of sensory neuropathy. Fatty replacements in the distal lower leg muscles were more severe than in the thigh muscles. Although the symptoms and signs of this patient harboring slow nerve conduction velocities suggested the possibility of demyelinating neuropathy, a distal sural nerve biopsy was compatible with axonal neuropathy. Immunohistochemical analysis revealed that the patient has a low level of PLEKHG5 in the distal sural nerve and an in vitro assay suggested that the mutant proteins have a defect in activating the NF-κB signaling pathway. CONCLUSIONS: This study identifies compound heterozygous PLEKHG5 mutations as the cause of RI-CMT. We suggest that PLEKHG5 might play a role in the peripheral motor and sensory nervous system. This study expands the phenotypic spectrum of PLEKHG5 mutations.