Clinical Interpretation of Sequence Variants.

Clinical interpretation of DNA sequence variants is a critical step in reporting clinical genetic testing results. Application of next-generation sequencing technology in molecular genetic testing has facilitated diagnoses of genetic disorders in clinical practice. However, the large number of DNA sequence variants detected in clinical specimens, many of which have never been seen before, make clinical interpretation challenging. Recommendations by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) have been widely adopted by clinical laboratories around the world to guide clinical interpretation of sequence variants. The ClinGen Sequence Variant Interpretation Working Group and various disease-specific variant curation expert panels have also developed specifications for the ACMG/AMP recommendations. Despite these efforts to standardize variant interpretation in clinical practice, different laboratories may subjectively use professional judgment to determine which criteria are applicable when classifying a variant. In addition, clinicians and researchers who are not familiar with the variant interpretation process may have difficulty understanding clinical genetic reports and communicating the clinical significance of genetic testing results. Here we provide a step-by-step protocol for clinical interpretation of sequence variants, including practical examples. By following this protocol, clinical laboratory geneticists can interpret the clinical significance of sequence variants according to the ACMG/AMP recommendations and ClinGen framework. Furthermore, this article will help clinicians and researchers to understand variant classification in clinical genetic testing reports and evaluate the quality of the reports. © 2020 by John Wiley & Sons, Inc. Basic Protocol: Interpreting the clinical significance of sequence variants Support Protocol: Reevaluating the clinical significance of sequence variants.

[Pharyngogastric or pharyngocolonic anastomosis in esophageal reconstruction for hypopharyngeal cancer or esophageal disease].

OBJECTIVE: To evaluate the surgical indications and postoperative morbidity of pharyngogastric anastomosis or pharyngocolonic anastomosis in esophageal reconstruction for advanced hypopharyngeal and cervical esophageal neoplasms or diffuse corrosive hypopharyngoesophageal stricture. METHOD: Retrospectively analysis the experience and results of 52 patients undergoing esophageal reconstruction with pharyngogastric anastomosis and 66 patients with pharyngocolonic anastomosis. In the group of neoplasms, total esophagectomy with pharyngogastric anastomoses in 52 cases and with pharyngo-colonic anastomosis in 35 cases. Thirty-one cases with diffuse corrosive hypopharyngoesophageal stricture were treated by pharyngo-colonic anastomosis without resection of the strictured intrathoracic esophagus. RESULT: In the group of neoplasm E, preservation of laryngeal functions in pharyngogastric anastomoses was performed in 28/52 cases and that of in pharyngo-colonic anastomosis was in 18/35 cases. There was no significant difference in preservation of laryngeal functions between two groups (P > 0.05). Pharyngocutaneous fistula was happened in 23 patients which significant higher in the group of pharyngocolonic anastomosis (17/66 cases) than that of pharynogogastric anasromoses (5/52 cases) (P < 0.05). Gastric reflux was presented in 19 cases and there was significant higher in pharyngogastric anastomoses (16/52 cases) than that of (3/66 cases) (P < 0.05). CONCLUSION: Substitution of esophagus with stomach or colon can completely removed the neoplasms of hypopharynx or cervical esophagus and preserved laryngeal functions in selected patients. But gastric reflux is a challenging reconstructive problem in pharyngogastric anastomosis. Pharyngocolonic anastomosis should take into consideration to patients with extensive neoplasms and diffuse corrosive stricture or probably preserved the laryngeal functions. However, the swallow function is weak and the incidence of pharyngocolonic fistula is higher than that of pharyngogastric anastomosis.

Effects of silencing Id-1 in cell culture of human adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a slow growing but highly invasive cancer with a high recurrence rate. Id (inhibitor of DNA binding) proteins are dominant regulators of basic helix-loop-helix transcription factors that control malignant cell behavior in many different tissues. This study aimed to identify the potential role of inhibiting DNA binding-1 (Id-1) in human salivary adenoid cystic carcinoma (SACC) progression. First, we compared the Id-1 protein expression in a human salivary adenoid cystic carcinoma cell line (ACCM) against three other cell lines and found that Id-1 protein expression in ACCM to be significantly higher. Then we measured Id-1 mRNA and protein expression in ACCM before and after RNA interference (RNAi), which showed successful inhibition of Id-1. Further studies then demonstrated that the proliferation and invasiveness of ACCM cells were dramatically down-regulated, and increased numbers of apoptotic cells were detected after Id-1 silencing. Consequently, our data suggest that Id-1 is a potential target in the treatment of human salivary adenoid cystic carcinoma.

[Diagnosis and surgical treatment of cervical lymphangioma].

OBJECTIVE: To discuss the methods of surgical treatment and their timing choices of cervical lymphangioma. METHODS: A retrospective review of 53 patients with cervicofacial lymphangioma were treated surgically from July 1990 to December 2008. The age at operation was from 6.5 months to 41 years old (median age was 2 years old and 3 months). Eighteen (34.0%) lesions were located in the suprahyoid region and 35 (66.0%) lesions in the infrahyoid region. The diameter of lesion ranged from 3.3 to 8.2 cm (average: 4.4 cm). Neck mass was the sole symptom for 77.4% (41/53) cases. Nine patients presented with life-threatening complications including intracystic hemorrhage in 2 cases/times, infection and rapid increase in tumor size in 5 cases/times, dysphagia in 2 cases/times and respiratory obstruction in 4 cases/times. Color Doppler ultrasound was used to diagnose all patients pre-operatively. Computed tomography (CT) was used in 11 cases and magnetic resonance imaging (MRI) in 21 cases for differential diagnosis. RESULTS: The patients were treated by complete resection in 34 cases and subtotal resection in 8 cases. But partial resection in 11 (20.8%) cases developed a residual or recurrent lesion within 9 months to 5 years post-operation, including 7 cases in suprahyoid region and 4 cases in infrahyoid region. The rate of residual or recurrent lesions was significantly higher in the suprahyoid region (7/18) than that in the infrahyoid region (4/35) (chi(2) test, P < 0.05). The peri-operative complications were paralyses of mandibular branch of facial nerve, Horner's syndrome, secondary hemorrhage, fluid collection at resection site, local infection and parotid fistula in 1 case respectively. Respiratory distress caused by edema of tongue was present in 2 cases. All of them were cured conservatively. The pathological diagnosis was confirmed as capillary lymphangioma in 19 cases and cystic lymphangioma in 34 cases. CONCLUSION: The localization and extent of cervical lymphangioma are the most important determining factors for a successful surgical resection. Although complete excision is the ideal treatment for cervicofacial lymphangioma, this should not be attempted if lesions are too large and neighboring structures liable to injury. The surgeons should be aware of the limitations and potential surgical complications in certain instances.