title: Germline mutations and genotype-phenotype correlation in Asian Indian patients with pheochromocytoma and paraganglioma.
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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India reshmap9@gmail.com.
authors.forename: Reshma
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authors.affiliation: Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
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authors.affiliation: Department of EndocrinologyVydehi Institute of Medical Sciences and Research Centre, Bangalore, Karnataka, India.
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authors.affiliation: Department of EndocrinologyMahatma Gandhi Hospital and Medical College, Jaipur, Rajasthan, India.
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authors.affiliation: Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
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authors.affiliation: Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
authors.forename: Shruti
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authors.affiliation: Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
authors.forename: Sandhya
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authors.affiliation: Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
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authors.affiliation: PathologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
authors.forename: Gwendolyn
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authors.affiliation: PathologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
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authors.affiliation: PathologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
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authors.affiliation: Radiation Medicine CentreBhabha Atomic Research Centre, Mumbai, Maharashtra, India.
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authors.affiliation: Department of Uro-oncologyTata Memorial Hospital, Mumbai, Maharashtra, India.
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authors.affiliation: Department of EndocrinologyPostgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
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authors.affiliation: Department of EndocrinologyPostgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
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authors.affiliation: Department of EndocrinologyJawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India.
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authors.affiliation: Endocrine UnitDepartment of Medicine, Goa Medical College, Bambolim, Goa, India.
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authors.affiliation: Department of MedicineKannur Medical College and Hospital, Kannur, Kerala, India.
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authors.affiliation: Department of EndocrinologyPt. B.D. Sharma PGIMS, Rohtak, Haryana, India.
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authors.affiliation: Division of Pediatric EndocrinologyBai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India.
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authors.affiliation: Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
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authors.affiliation: Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
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authors.affiliation: Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
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authors.affiliation: Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
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authors.affiliation: Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India.
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mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000367:Age Factors; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics* / Q000473:pathology; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C108096:SDHC protein, human; C491545:SDHD protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C497446:VHL protein, human