Prioritizing genetic testing in patients with kallmann syndrome using clinical phenotypes.

Details

Serval ID
serval:BIB_A457B2246597
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Prioritizing genetic testing in patients with kallmann syndrome using clinical phenotypes.
Journal
Journal of Clinical Endocrinology and Metabolism
Author(s)
Costa-Barbosa F.A., Balasubramanian R., Keefe K.W., Shaw N.D., Al-Tassan N., Plummer L., Dwyer A.A., Buck C.L., Choi J.H., Seminara S.B., Quinton R., Monies D., Meyer B., Hall J.E., Pitteloud N., Crowley W.F.
ISSN
1945-7197 (Electronic)
ISSN-L
0021-972X
Publication state
Published
Issued date
2013
Volume
98
Number
5
Pages
E943-E953
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Context: The complexity of genetic testing in Kallmann syndrome (KS) is growing and costly. Thus, it is important to leverage the clinical evaluations of KS patients to prioritize genetic screening. Objective: The objective of the study was to determine which reproductive and nonreproductive phenotypes of KS subjects have implications for specific gene mutations. Subjects: Two hundred nineteen KS patients were studied: 151 with identified rare sequence variants (RSVs) in 8 genes known to cause KS (KAL1, NELF, CHD7, HS6ST1, FGF8/FGFR1, or PROK2/PROKR2) and 68 KS subjects who remain RSV negative for all 8 genes. Main Outcome Measures: Reproductive and nonreproductive phenotypes within each genetic group were measured. Results: Male KS subjects with KAL1 RSVs displayed the most severe reproductive phenotype with testicular volumes (TVs) at presentation of 1.5 ± 0.1 mL vs 3.7 ± 0.3 mL, P < .05 vs all non-KAL1 probands. In both sexes, synkinesia was enriched but not unique to patients with KAL1 RSVs compared with KAL1-negative probands (43% vs 12%; P < .05). Similarly, dental agenesis and digital bone abnormalities were enriched in patients with RSVs in the FGF8/FGFR1 signaling pathway compared with all other gene groups combined (39% vs 4% and 23% vs 0%; P < .05, respectively). Hearing loss marked the probands with CHD7 RSVs (40% vs 13% in non-CHD7 probands; P < .05). Renal agenesis and cleft lip/palate did not emerge as statistically significant phenotypic predictors. Conclusions: Certain clinical features in men and women are highly associated with genetic causes of KS. Synkinesia (KAL1), dental agenesis (FGF8/FGFR1), digital bony abnormalities (FGF8/FGFR1), and hearing loss (CHD7) can be useful for prioritizing genetic screening.
Pubmed
Web of science
Open Access
Yes
Create date
13/06/2013 17:10
Last modification date
20/08/2019 15:09
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