A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1

Abstract Background Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECTIN4 gene. Objective The main objective of the study was to identify the pathogenic sequence variant(s) for family screening and identification of carriers. Methods In the present study, the authors have investigated a large consanguineous family of Pakistani origin segregating autosomal recessive EDSS1. All the coding exons of the NECTIN4 gene were directly sequenced using gene-specific primers. Results The affected individuals presented the classical EDSS1 clinical features including sparse hair, hypoplastic nails with thick flat discolored nail plates, peg-shaped, conical, and widely spaced teeth with enamel hypoplasia, proximal cutaneous syndactyly of fingers and toes. Sequence analysis of the coding region of the NECTIN4 identified a novel nonsense variant [c.163C>T; p.(Arg55*)] in exon-2 of the gene. Computational analysis of protein structure revealed that the variant induced premature termination at Arg55 located in Ig-like V-loop region leading to loss of Ig-C2 type domains and transmembrane region, and most likely Nectin-4 function will be lost. Study limitation Gene expression studies are absent that would have strengthened the findings of computational analysis. Conclusion The present study expanded the phenotypic and mutation spectrum of the NECTIN4 gene. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.

Malignant transformations in ovarian teratomas: a report of four cases.

Mature cystic teratoma (MCT) is a common ovarian neoplasm in young females. A secondary malignant transformation occurs rarely in cystic teratomas at an older age. These secondary malignant neoplasms most commonly are squamous cell carcinomas (SCCs). Various mechanisms are reported, but the exact aetiology is unknown. We report three cases of SCC arising in cystic teratoma and one case of papillary thyroid neoplasm as secondary transformation. The SCCs were arising from the cyst wall, while the papillary thyroid malignancy arose from the normal-looking thyroid epithelium. Histologically, all SCC cases were poorly differentiated. Poor prognostic features for secondary transformations include size more than 10 cm, older age and rapid growth. Data is scarce regarding their appropriate treatment. However, surgical debulking is necessary. Platinum-based adjuvant regimens and taxanes are recommended in cases of advanced disease. In this paper we review and share our experience with this rare disorder.

FDG-PET scan in assessing lymphomas and the application of Deauville Criteria.

OBJECTIVE: To evaluate the role of Fluorine-18-fluorodexoyglucose Positron Emission Tomography (FDG-PET) scan in staging and its implications on the treatment of lymphoma, and to study the concordance between visual assessment and Deauville criteria for the interpretation of interim scans. METHODS: The prospective single-arm experimental study was conducted at the Shaukat Khanum Memorial Cancer Hospital, Lahore, from May 2011 to October 2011. It comprised 53 newly diagnosed lymphoma patients who agreed to participate in the study. All patients underwent scans with contrast-enhanced computerised tomography at baseline. Treatment plan was formulated based on the final stage. Interim scans were acquired after 2 cycles of chemotherapy and were reported using visual criteria and compared with the 5-point Deauville criteria. Score of 1-3 was taken as disease-negative, while 4-5 was taken as disease-positive. SPSS 19 was used for statistical analysis. RESULTS: Of the 53 patients, 35 (66%) had Hodgkin's Lymphoma, while 18 (34%) had Non-Hodgkin's Lymphoma. Scans resulted in disease upstaging in 4 (7.5%) patients, and detecting increased disease burden in 12 (23%). On interim scans, complete remission was achieved in 38 (71%) patients (Deauville score 1-3); 12(23%) showed partial response (Deauville score 4-5); and 3 (6%) had progression. Kappa test was statistically significant (kappa 0.856; p <0.001). CONCLUSION: The positron emission tomography helped to upstage lymphoma and reflected increased disease burden. The Deauville criteria correlated very well with visual assessment criteria and can be applied in the patient population.