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No difference in phenotype of the main D utch SDHD founder mutations
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 ge...
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Published in: | Clinical endocrinology (Oxford) 2013-12, Vol.79 (6), p.824-831 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 0300-0664 1365-2265 |
DOI: | 10.1111/cen.12223 |