Germline mutations and genotype–phenotype correlation in Asian Indian patients with pheochromocytoma and paraganglioma. Issue 4 (October 2016)

• Record Type: Journal Article
• Authors: Pandit, Reshma; Khadilkar, Kranti; Sarathi, Vijaya; Kasaliwal, Rajeev; Goroshi, Manjunath; Khare, Shruti; Nair, Sandhya; Raghavan, Vijaya; Dalvi, Abhay; Hira, Priya; Fernandes, Gwendolyn; Sathe, Pragati; Rojekar, Amey; Malhotra, Gaurav; Bakshi, Ganesh; Prakash, Gagan; Bhansali, Anil; Walia, Rama; Kamalanathan, Sadishkumar; Sahoo, Jayaprakash; Desai, Ankush; Bhagwat, Nikhil; Mappa, Prashanth; Rajput, Rajesh; Chandrashekhar, Sudha Rao; Shivane, Vyankatesh; Menon, Padma; Lila, Anurag; Bandgar, Tushar; Shah, Nalini
• Is Part Of: European journal of endocrinology. Volume 175:Issue 4(2016)
• Page Start: 311
• Page End: 323
• Publication Date: 2016-10
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/EJE-16-0126
• Languages: English
• ISSNs: 0804-4643

Abstract

Abstract : Background: Genetic aetiology of pheochromocytoma (PCC) and paraganglioma (PGL) is increasingly being studied; however, Asian Indian data on this aspect are scarce. Objective: To study the prevalence of germline mutations and genotype–phenotype correlation in Asian Indian PCC/PGL patients. Design: In this study, 150 index patients (M:F, 73:77) with PCC/PGL were evaluated. Phenotypic data were collected. Germline mutations in five susceptibility genes ( RET, VHL, SDHB, SDHD and SDHC ) were tested by sequencing and NF1 was diagnosed according to phenotype. Result: Of the total population, 49 (32.7%) PCC/PGL patients had germline mutations ( VHL : 23 (15.3%), RET : 13 (8.7%), SDHB : 9 (6%), SDHD : 2 (1.3%) and NF1 : 2 (1.3%)). Amongst the 30 patients with familial and/or syndromic presentation, all had germline mutations ( VHL : 14 (46.7%), RET : 13 (43.3%), SDHB : 1 (3.3%) and NF1: 2 (6.7%)). Out of 120 patients with apparently sporadic presentation, 19 (15.8%) had a germline mutation ( VHL : 9 (7.5%), SDHB : 8 (6.7%) and SDHD : 2 (1.7%)). Mutation carriers were younger (29.9 ± 14.5 years vs 36.8 ± 14.9; P = 0.01) and had a higher prevalence of bilateral PCC (26.5% vs 2.9%, P < 0.001) and multifocal tumours (12.2% vs 0.96%, P = 0.06). Based on syndromic features, metastasis, location and number of tumours, around 96% mutations in our cohort could be detected by appropriately selected single gene testing. Conclusion: Asian Indians with PCC/PGL differ from Western cohorts in having preponderance of VHL mutations in multifocal tumours and apparently sporadic unilateral PCC. Syndromic presentation, metastasis, location and number of PCC/PGL can be effectively used for guiding genetic prioritisation.