Ultra-low-coverage genome-wide association study-insights into gestational age using 17,844 embryo samples with preimplantation genetic testing.

BACKGROUND: Very low-coverage (0.1 to 1×) whole genome sequencing (WGS) has become a promising and affordable approach to discover genomic variants of human populations for genome-wide association study (GWAS). To support genetic screening using preimplantation genetic testing (PGT) in a large population, the sequencing coverage goes below 0.1× to an ultra-low level. However, the feasibility and effectiveness of ultra-low-coverage WGS (ulcWGS) for GWAS remains undetermined. METHODS: We built a pipeline to carry out analysis of ulcWGS data for GWAS. To examine its effectiveness, we benchmarked the accuracy of genotype imputation at the combination of different coverages below 0.1× and sample sizes from 2000 to 16,000, using 17,844 embryo PGT samples with approximately 0.04× average coverage and the standard Chinese sample HG005 with known genotypes. We then applied the imputed genotypes of 1744 transferred embryos who have gestational ages and complete follow-up records to GWAS. RESULTS: The accuracy of genotype imputation under ultra-low coverage can be improved by increasing the sample size and applying a set of filters. From 1744 born embryos, we identified 11 genomic risk loci associated with gestational ages and 166 genes mapped to these loci according to positional, expression quantitative trait locus, and chromatin interaction strategies. Among these mapped genes, CRHBP, ICAM1, and OXTR were more frequently reported as preterm birth related. By joint analysis of gene expression data from previous studies, we constructed interrelationships of mainly CRHBP, ICAM1, PLAGL1, DNMT1, CNTLN, DKK1, and EGR2 with preterm birth, infant disease, and breast cancer. CONCLUSIONS: This study not only demonstrates that ulcWGS could achieve relatively high accuracy of adequate genotype imputation and is capable of GWAS, but also provides insights into the associations between gestational age and genetic variations of the fetal embryos from Chinese population.

Accuracy of radiographic measurements for implant planning using cone-beam and helical computer tomography.

AIM: The aim of the present study was to compare the accuracy of radiographic measurements for dental implants planning using cone-beam computed tomography (CBCT) and helical computed tomography (HCT). METHODS: Six pig ribs were wrapped by putty impression material, with radiographic markers placed. Two CBCT and an HCT were taken following the standard protocols. Twenty-five locations were selected, with vertical and horizontal dimensions measured using the default software, as well as on the processed HCT films by a digital caliper. The actual dimensions of the ribs measured by the digital caliper served as the control. Differences between radiographic dimensions and the actual dimensions were tested by two-way analysis of variance. RESULTS: No differences were found between measurements made by CBCT and HCT images using the default software (P > 0.05). However, both measurements were statistically-significantly lower than the control (P < 0.001), and the mean difference was 0.3 mm. Measurements made on HCT films were statistically-significantly greater than the control (P < 0.001), and the mean difference was 0.5 mm. CONCLUSION: The accuracy of CBCT and HCT are similar, and both are reliable tools for implant planning. It is preferable to perform the planning using default software, rather than making direct measurements on films.

A consecutive case series of nevoid basal cell carcinoma syndrome affecting the Hong Kong Chinese.

OBJECTIVES: To identify the clinical and radiologic features of nevoid basal cell carcinoma syndrome (NBCCS) in the Hong Kong Chinese, particularly those of keratocystic odontogenic tumors (KCOTs), at first presentation at a dental hospital. STUDY DESIGN: A consecutive case series of NBCCS was identified in the University of Hong Kong Dental Hospital. RESULTS: All 5 Hong Kong NBCCS cases presented with symptoms arising from their KCOTs; 3 with swelling, 3 with pain, and 2 with nasal discharge. The cases exhibited 4 major features (KCOTs, calcified falx cerebri, palmar/plantar pits, and basal cell carcinoma) and 4 minor features (sella bridges, bossing, hypertelorism, and mandibular prognathism). The KCOTs were all unilocular. The tumors displaced teeth in 4 cases. Only 1 had root resorption. There were 2 nonsyndromic cases with multiple KCOTs. CONCLUSIONS: The unilocular presentation of the syndromic KCOTs was significantly greater than that of the solitary cases, arising within the same community over the same period. The other presenting features of the syndromic KCOTs did not differ from the solitary KCOTs. The recurrence rate of syndromic KCOTs was significantly greater than of the solitary KCOTs. Nonsyndromic cases with multiple KCOTs could be more common in East Asians.

Comparison of ridge mapping and cone beam computed tomography for planning dental implant therapy.

PURPOSE: The aim of this study was to compare the relative accuracy of the ridge-mapping method against that of standard computed tomography (CT). MATERIALS AND METHODS: Consecutive partially edentulous subjects requiring dental implants were recruited for this prospective study. Vacuum-formed radiographic templates with reference points were used for the ridge-mapping procedure and CT scanning. Ridge-mapping measurements were translated onto study models, which were subjected to CT scanning with the templates in place. CT images of the study models obtained from the ridge-mapping method were compared with CT images of the subjects. The data were analyzed with the Wilcoxon signed-rank test. Differences were considered significant if P < .05. RESULTS: Fourteen subjects were recruited and a total of 21 implant sites were evaluated. The ridge dimensions measured by the bone-mapping method and CT scanning were significantly different (P < .05). The mean difference ranged from 0.3 to 0.5 mm, and large variations were found in the sulcus region. CONCLUSION: Measurements of the alveolar bone dimension using the ridge-mapping method are different from CT scanning, with a mean difference of about 0.4 mm.

Haemoglobin level, proportion of haemoglobin Bart's and haemoglobin Portland in fetuses affected by homozygous α0-thalassemia from 12 to 40 weeks' gestation.

OBJECTIVES: To determine haematological parameters in fetuses affected by homozygous α(0)-thalassemia. METHODS: This was a cross-sectional retrospective study reviewing 546 blood samples (268 fetal and 278 neonatal cord) being collected between 1993 and 2006, from 12 weeks' gestation onwards for any indication, including the prenatal diagnosis of homozygous α(0)-thalassemia, other haematological disorders, hydrops or aneuploidy. The proportion of haemoglobin (Hb) fractions was determined by electrophoresis of haemolysate on cellulose acetate in all samples. RESULTS: There were significant differences in the haematological parameters between homozygous α(0)-thalassemia (n = 183) and control (n = 363) which were either heterozygous α(0)-thalassemia (alpha thalassemia trait) or normal. In homozygous α(0)-thalassemia, the median Hb level, proportion of Hb Bart's (γ(4)) and Hb Portland 1(ζ(2)γ(2)) were 6.4 g/dL, 77.5% and 22.5%, respectively. While the Hb level and the proportion of Hb Bart's increased significantly with gestation, the proportion of Hb Portland 1 decreased. The Hb level contributed by Hb Portland 1 remained around 1.4 g/dL throughout gestation. The proportion of mild, moderate and severe anaemia in the affected fetuses was 27.5, 32.7 and 39.8%, respectively. There was no significant difference in these proportions across different gestation (P = 0.231). There were no differences in the haematological parameters between hydropic and non-hydropic fetuses. CONCLUSION: Although the degree of anaemia is mild in around one-quarter of the affected fetuses, the contribution by Hb Portland 1 (ζ(2)γ(2)) to the Hb level was very low throughout gestation, and the affected fetuses may therefore be at risk for hypoxia.

Patterns of tooth loss in young adult Hong Kong Chinese patients in 1983 and 1998.

OBJECTIVE: To describe and compare patterns of tooth loss in 2 groups of 21- to 25-year-old Hong Kong Chinese patients examined 15 years apart. MATERIALS AND METHODS: The panoramic radiographs of consecutive young adult patients who attended the primary care department of the Dental School of the University of Hong Kong in 1983 and 1998 were reviewed. RESULTS: The proportions of patients with full dentition were 36.0% in 1983 and 45.1% in 1998. However, when third molars were excluded, the proportions were 44.3% and 62.3%, respectively. The prevalence of missing first molars was 10.5% and 3.2% for the 1983 and 1998 groups, respectively, whereas that for missing third molars was 13.5% and 17.9% and that for missing premolars was 1.9% and 2.4%, respectively; all of the differences were statistically significant (p < 0.01). Although the first molars, especially the lower first molars, were at greatest risk of being lost in both groups, the prevalence of missing first molars fell substantially (10.5% in 1983, 3.2% in 1998); in contrast, the prevalence of missing premolars and third molars increased. CONCLUSIONS: The decline in the prevalence of missing first molars may in part reflect the efficacy of toothbrushing, whereas the increase in missing premolars and third molars reflects increases in orthodontic and oral surgical activity in the intervening period.

The use of lipiodol in spiral tomography for dental implant imaging.

Preoperative radiographic assessment is mandatory for the meticulous treatment planning and successful placement of implants. The precise topographical evaluation of selected implant sites, apart from the most straightforward cases, requires tomographic examination with the use of diagnostic radiographic templates. The incorporation of various radiopaque materials such as barium sulphate and lead foil as radiographic markers had not been entirely satisfactory. A new contrast medium, Lipiodol ethiodized oil (Laboratoire Guerbet, Paris, France), can easily be mixed with the monomer of autopolymerizing acrylic resin. The resultant acrylic template has several advantages. The tomographic images (Scanora; Soredex Orion Corporation, Helsinki, Finland) are radiographically homogenous and show the contour of the future prosthesis, the angulation of the planned implant, and the thickness of the soft tissue. In addition, the radiopaque template is optically transparent (with a slight yellow tint), which facilitates good visibility of surgical sites when the template is modified to become the surgical guide for implant placement. This transparent template can be further modified for implant position registration at the time of surgery. Because this multipurpose template is simple to construct and inexpensive, it can be recommended for routine use in implant dentistry.