Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1 gene.

Segmental progeroid syndromes with lipodystrophy are extremely rare, heterogeneous, and complex multi-system disorders that are characterized by phenotypic features of premature aging affecting various tissues and organs. In this study, we present a "sporadic/isolated" Japanese woman who was ultimately diagnosed with mandibular hypoplasia, deafness, progeroid features, and progressive lipodystrophy (MDPL) syndrome (MIM #615381) using whole exome sequencing analysis. She had been suspected as having atypical Werner syndrome and/or progeroid syndrome based on observations spanning a 30-year period; however, repeated genetic testing by Sanger sequencing did not identify any causative mutation related to various subtypes of congenital partial lipodystrophy (CPLD) and/or mandibular dysplasia with lipodystrophy (MAD). Recently, MDPL syndrome has been described as a new entity showing progressive lipodystrophy. Furthermore, polymerase delta 1 (POLD1) gene mutations on chromosome 19 have been identified in patients with MDPL syndrome. To date, 21 cases with POLD1-related MDPL syndrome have been reported worldwide, albeit almost entirely of European origin. Here, we identified a de novo mutation in exon 15 (p.Ser605del) of the POLD1 gene in a Japanese case by whole exome sequencing. To the best of our knowledge, this is the first identified case of MDPL syndrome in Japan. Our results provide further evidence that mutations in POLD1 are responsible for MDPL syndrome and serve as a common genetic determinant across different ethnicities.

A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy characterized by clinical and genetic heterogeneity. Although more than 30 loci harboring CMT-causing mutations have been identified, many other genes still remain to be discovered for many affected individuals. For two consanguineous families with CMT (axonal and mixed phenotypes), a parametric linkage analysis using genome-wide SNP chip identified a 4.3 Mb region on 12q24 showing a maximum multipoint LOD score of 4.23. Subsequent whole-genome sequencing study in one of the probands, followed by mutation screening in the two families, revealed a disease-specific 5 bp deletion (c.247-10_247-6delCACTC) in a splicing element (pyrimidine tract) of intron 2 adjacent to the third exon of cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1), which is a component of mitochondrial respiratory complex IV (cytochrome c oxidase [COX]), within the autozygous linkage region. Functional analysis showed that expression of COX6A1 in peripheral white blood cells from the affected individuals and COX activity in their EB-virus-transformed lymphoblastoid cell lines were significantly reduced. In addition, Cox6a1-null mice showed significantly reduced COX activity and neurogenic muscular atrophy leading to a difficulty in walking. Those data indicated that COX6A1 mutation causes the autosomal-recessive axonal or mixed CMT.

Glycemic control and number of natural teeth: analysis of cross-sectional Japanese employment-based dental insurance claims and medical check-up data.

AIM: Diabetes mellitus is a well-known risk factor for onset and progression of periodontal disease. However, the continuous relationship between glycemic control and the number of natural teeth has not been well characterized in large-scale studies. We aimed to determine whether the glycated hemoglobin A1c (HbA1c) level and fasting plasma glucose (FPG) are associated with the number of natural teeth. METHODS: A cross-sectional study: A database comprising employment-based health insurance claim and medical check-up data from 706,150 participants between April 2015 and March 2016 in Japan. The exclusion criteria included missing data regarding dental receipts, number of natural teeth, HbA1c, smoking status, and age < 20 years. Ultimately, 233,567 individuals were analyzed. The participants were allocated to five groups according to their HbA1c and three groups according to their FPG, and then the number of natural teeth were compared. RESULTS: Higher HbA1c was associated with fewer teeth in participants ≥ 30 years of age (P for trend < 0.001). Higher FPG was associated with fewer teeth between 30 and 69 years of age (P for trend < 0.001). Participants with impaired fasting glucose was already at risk for fewer teeth between 40 and 69 years of age than those with normal FPG. CONCLUSIONS: Glycemic control is strongly associated with the number of natural teeth in the real-world setting. Furthermore, there are continuous relationships of HbA1c and FPG with number of natural teeth including individual with impaired fasting glucose. These data emphasize the importance of glycemic control and appropriate oral care for the protection against tooth loss. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00533-2.

Real-world evidence of the impact of obesity on residual teeth in the Japanese population: A cross-sectional study.

BACKGROUND: Tooth loss is associated with nutritional status and significantly affects quality of life, particularly in older individuals. To date, several studies reveal that a high BMI is associated with tooth loss. However, there is a lack of large-scale studies that examined the impact of obesity on residual teeth with respect to age and tooth positions. OBJECTIVE: We assessed the impact of obesity on the number and position of residual teeth by age groups using large scale of Japanese database. METHODS: This was a cross-sectional study of 706150 subjects that were included in the database that combined the data from health insurance claims and health check-up, those lacking information about BMI, HbA1c level, smoking status, and the number of residual teeth were excluded. Thus, a total of 233517 aged 20-74 years were included. Subjects were classified into 4 categories based on BMI, and the number of teeth was compared between age-groups. The percentage of subjects with residual teeth in each position was compared between groups with obesity (BMI ≥25.0 kg/m2) and non-obesity. Logistic regression analysis was performed to clarify whether obesity predicts having <24 teeth. RESULTS: Higher BMI was associated with fewer teeth over 40s (P for trend <0.0001 when <70s). Obesity was associated with the reduction of residual teeth in the maxillary; specifically, the molars were affected over the age 30. Smoking status further affected tooth loss at positions that were not affected by obesity alone. After adjusting for age, sex, smoking status, and HbA1c ≥6.5%, obesity remained an independent predictive factor for having <24 teeth (ORs: 1.35, 95% CIs: 1.30-1.40). CONCLUSIONS: We found that an increase in BMI was associated with a decrease in the number of residual teeth from younger ages independently of smoking status and diabetes in the large scale of Japanese database.

Contrast medium-induced severe thrombocytopenia in patient on maintenance hemodialysis: a case report and literature review.

A 43-year-old male patient on maintenance hemodialysis had an enhanced computed tomography scan examination with iohexol for the first time 10 min before regular hemodialysis therapy. At the start of hemodialysis, no symptoms were observed, and the platelet count was 148,000/µl. Approximately 1 h after starting hemodialysis, dyspnea and chest discomfort appeared. Since oxygen saturation of the peripheral artery decreased to 87%, oxygen administration was immediately started while continuing hemodialysis therapy. Furthermore, gingival hemorrhage was observed, and the platelet count decreased to 5000/µl. We were carefully monitoring his conditions while continuing hemodialysis and oxygen administration, but no further deterioration was observed. Thereafter, these symptoms and severe thrombocytopenia gradually improved without additional treatment. At the end of hemodialysis, these symptoms completely disappeared. As well, the platelet count recovered to 35,000/µl at the end of hemodialysis and increased to 92,000/µl the next morning. From the clinical course, we diagnosed with contrast medium-induced thrombocytopenia. Acute thrombocytopenia is a rare complication induced by the contrast medium. Until now, 16 cases on contrast medium-induced thrombocytopenia have been reported. Our case spontaneously recovered from severe thrombocytopenia relatively earlier than previous reports. Our patient started hemodialysis therapy 10 min after an enhanced computed tomography examination. Early removal of contrast medium by hemodialysis might be associated with early improvement. We should acknowledge that contrast media have potential to induce severe thrombocytopenia, even in patients on maintenance hemodialysis.

A high-fiber, low-fat diet improves periodontal disease markers in high-risk subjects: a pilot study.

Periodontal disease is related to aging, smoking habits, diabetes mellitus, and systemic inflammation. However, there remains limited evidence about causality from intervention studies. An effective diet for prevention of periodontal disease has not been well established. The current study was an intervention study examining the effects of a high-fiber, low-fat diet on periodontal disease markers in high-risk subjects. Forty-seven volunteers were interviewed for recruitment into the study. Twenty-one volunteers with a body mass index of at least 25.0 kg/m(2) or with impaired glucose tolerance were enrolled in the study. After a 2- to 3-week run-in period, subjects were provided with a test meal consisting of high fiber and low fat (30 kcal/kg of ideal body weight) 3 times a day for 8 weeks and followed by a regular diet for 24 weeks. Four hundred twenty-five teeth from 17 subjects were analyzed. Periodontal disease markers assessed as probing depth (2.28 vs 2.21 vs 2.13 mm; P < .0001), clinical attachment loss (6.11 vs 6.06 vs 5.98 mm; P < .0001), and bleeding on probing (16.2 vs 13.2 vs 14.6 %; P = .005) showed significant reductions after the test-meal period, and these improvements persisted until the follow-up period. Body weight (P < .0001), HbA1c (P < .0001), and high-sensitivity C-reactive protein (P = .038) levels showed improvement after the test-meal period; they returned to baseline levels after the follow-up period. In conclusion, treatment with a high-fiber, low-fat diet for 8 weeks effectively improved periodontal disease markers as well as metabolic profiles, at least in part, by effects other than the reduction of total energy intake.