Browsing by Author "Basnayake, S."

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Characteristic dental pattern with hypodontia and short roots in Fraser Syndrome
(Wiley-Liss, 2020) Kunz, F.; Kayserili, H.; Midro, A.; de Silva, D.; Basnayake, S.; Güven, Y.; Borys, J.; Schanze, D.; Stellzig-Eisenhauer, A.; Bloch-Zupan, A.; Zenker, M.
ABSTRACT:Fraser syndrome (FS) is a rare autosomal recessive multiple congenital malformation syndrome characterized by cryptophthalmos, cutaneous syndactyly, renal agenesis, ambiguous genitalia, and laryngotracheal anomalies. It is caused by biallelic mutations of FRAS1, FREM2, and GRIP1 genes, encoding components of a protein complex that mediates embryonic epithelial-mesenchymal interactions. Anecdotal reports have described abnormal orodental findings in FS, but no study has as yet addressed the orodental findings of FS systematically. We reviewed dental radiographs of 10 unrelated patients with FS of different genetic etiologies. Dental anomalies were present in all patients with FS and included hypodontia, dental crowding, medial diastema, and retained teeth. A very consistent pattern of shortened dental roots of most permanent teeth as well as altered length/width ratio with shortened dental crowns of upper incisors was also identified. These findings suggest that the FRAS1-FREM complex mediates critical mesenchymal-epithelial interactions during dental crown and root development. The orodental findings of FS reported herein represent a previously underestimated manifestation of the disorder with significant impact on orodental health for affected individuals. Integration of dentists and orthodontists into the multidisciplinary team for management of FS is therefore recommended. KEYWORDS: Fraser syndrome; dental roots; hypodontia; orodental health; taurodontism.
Molecular diagnosis of Velocardiofacial Syndrome in a cohort of Sri Lankan patients
(Sri Lanka Medical Association, 2014) Thevarajan, I.; Ranaweera, D.M.; de Silva, D.; Prabodha, L.B.L.; Gunasekera, R.; Dias, D.K.; Nanayakkara, B.G.; Basnayake, S.; Jayathilake, M.; Chandrasekharan, N.V.
INTRODUCTION AND OBJECTIVES: Velocardiofacial Syndrome (VCFS) is caused by a 3 Mb deletion encompassing around 40 genes on chromosome 22qll.2. It is characterised by variable features including congenital malformations of the palate and heart, growth and developmental delay, immunological anomalies, hypocalcaemia and other problems. Clinical diagnosis is difficult due to its variability within and between families. Early diagnosis enables appropriate management of the affected cases. Objective was to establish a reliable and cost effective molecular diagnostic test for VCFS. METHODS: Nineteen clinically suspected patients with palatal and facial features suggestive of VCFS from Lady Ridgeway Hospital, Colombo and the Teaching hospital, Karapitiya were recruited following informed consent and prior ethical clearance. A semi-quantitative multiplex poiymerase chain reaction (PCR) was established to identify the deletion using dosage analysis. The PCR assay was carried out using DNA from patients (P), unaffected person (N) and a positive control (with a FISH confirmed deletion} using STS markers within the deleted region and CFTR (Cystic Fibrosis Transmembrane Regulatory Conductance) control primers outside the deleted region. Following agarose gel electrophoresis the PCR products were quantified. A ratio of P: N of 0.5 was taken to indicate a deletion while a ratio of 1 indicated absence of the deletion. RESULTS: Among nineteen clinically suspected VCFS cases, five cases had the deletion. CONCLUSIONS: This semi-quantitative PCR assay was able to identify.deletions in clinically suspected patients. However further validation is required before its clinical usage.
Sickle cell disease in Sri Lanka: clinical and molecular basis and the unanswered questions about disease severity
(BioMed Central., 2020) Darshana, T.; Bandara, D.; Nawarathne, U.; de Silva, U.; Costa, Y.; Pushpakumara, K.; Pathirage, S.; Basnayake, S.; Epa, C.; Dilrukshi, P.; Wijayawardena, M.; Anthony, A. A.; Rodrigo, R.; Manamperi, A.; Smith, F.; Allen, A.; Menzel, S.; Rees, D.; Premawardhena, A.
BACKGROUND: Though case reports and limited case series of Sickle cell disease in Sri Lanka have been reported previously, no attempt has been made hitherto to undertake a comprehensive genotypic-phenotypic analysis of this "rare" group of patients. RESULTS: All accessible Sickle cell disease patients, totaling 60, including, 51 Sickle β-thalassaemia and 9 homozygous sickle patients were enrolled from seven thalassaemia treatment centres between December 2016-March 2019. The majority of patients were of Sinhalese ethnicity (n = 52, 86.67%). Geographically, two prominent clusters were identified and the distribution of Sickle haemoglobin in the island contrasted markedly with the other haemoglobinopathies. 3/ 9 homozygous sickle patients and 3/ 51 Sickle β-thalassaemia patients were receiving regular transfusion. Joint pain was the commonest clinical symptom among all sickle cell disease patients (n = 39, 65.0%). Dactylitis was significantly more common in homozygous sickle patients compared with the Sickle β-thalassaemia groups (p 0.027). Two genetic backgrounds sickle mutation were identified namely, Arab Indian and Benin. Among the regulators of Foetal hemoglobin in Sickle patients of the present study rs1427407 G > T seemed to be the most prominent modifier, with a significant association with Foetal haemoglobin levels (p 0.04). CONCLUSIONS: Overall, the clinical course of the Asian version of Sickle cell disease in Sri Lanka appears to be milder than that described in India. KEYWORDS: Clinical; Genetic; Severity; Sickle cell; Sri Lanka.
A Unique syndrome with facial, cranial, dental and skeletal features: possible relationship to maternal chikungunya exposure or an unidentified genetic cause?
(Sri Lanka College of Paediatricians, 2015) de Silva, D.; Basnayake, S.; Gunasekara, R.; Smith, J. C.; Donnai, D.; Newman, B.
BACKGROUND:Six children from the western province of Sri Lanka, born between June 2007 and November 2008 have presented with a unique phenotype comprising distinctive facial features, skeletal abnormalities and variable intellectual disability. In four children the mother reported a clinical history of chikungunya infection (CHKV) during their first trimester. OBJECTIVE: • Describe the clinical and demographic features of affected cases • Identify a genetic basis using whole exome sequencing (WES) DESIGN, SETTING AND METHOD: Cases were recruited following informed consent from parents. Blood taken for DNA extraction and WES performed using the lllumina HiSeq 2500 platform. Reads were aligned to the human reference sequence hg19 and analysed using bioinformatics software. RESULTS: Four cases were females. Five were Sinhalese, one Tamil. None had parental consanguinity. Four mothers reported first trimester CHKV infection. Distinctive facial features (pinched face, downslanting eyes, turri-brachvcephalv, open mouth, lip retraction, V shaped dental arches and high mandibular angles), restriction of joint movements (small and large joints) and variable developmental delay were present. Review by a panel of experts revealed no syndrome diagnosis WES analysis on five cases did not identify a homozygous or compound heterozygous recessive or de novo dominant mutation of an autosomal gene. CONCLUSIONS: WES analysis did not identify a homozygous or compound heterozygous recessive or de novo dominant mutation of an autosomal gene.