Premium
No difference in phenotype of the main D utch SDHD founder mutations
Author(s) -
Hulsteijn L. T.,
den Dulk A. C.,
Hes F. J.,
Bayley J. P.,
Jansen J. C.,
Corssmit E. P. M.
Publication year - 2013
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12223
Subject(s) - sdhd , paraganglioma , medicine , mutation , genetics , genotype , pheochromocytoma , pathology , biology , germline mutation , gene
Summary Objective SDHD mutations predispose carriers to hereditary paraganglioma syndrome. The objective of this study was to assess the genotype–phenotype correlation of a large D utch cohort of SDHD mutation carriers and evaluate potential differences in clinical phenotypes due to specific SDHD gene mutations. Design Retrospective, descriptive single‐centre study. Patients All consecutive SDHD mutation carriers followed at the D epartment of E ndocrinology of the L eiden U niversity M edical C enter were included. Measurements Subjects were investigated according to structured protocols used for standard care, including repetitive biochemical and radiological screening for paragangliomas. Results Two hundred and one SDHD mutation carriers with a mean age at presentation of 42·6 ± 14·4 years and a mean follow‐up of 5·8 ± 5·4 years were evaluated. Eighty‐one percent carried the SDHD c.274 G > T (p. A sp92 T yr) mutation and 13% the SDHD c.416T>C (p. L eu139 P ro) mutation. No differences in clinical phenotype between these two specific SDHD mutations were found. Ninety‐one percent developed one or multiple paragangliomas in the head and neck region ( HNPGL s), of which the carotid body tumour was the most prevalent (85%). Eighteen carriers developed pheochromocytomas, fifteen sympathetic paragangliomas and nine carriers (4%) suffered from malignant paraganglioma. By end of follow‐up, sixteen SDHD mutation carriers (8%) displayed no biochemical or radiological evidence of manifest disease. Conclusions The two main D utch SDHD founder mutations do not differ in clinical expression. SDHD mutations are associated with the development of multiple HNPGL s and predominantly benign disease.