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@ARTICLE{Simm:136899,
author = {F. Simm and A. Griesbeck and D. Choukair and B. Weiß and
N. Paramasivam$^*$ and J. Klammt and M. Schlesner$^*$ and S.
Wiemann$^*$ and C. Martinez and G. F. Hoffmann and R. W.
Pfäffle and M. Bettendorf and G. A. Rappold},
title = {{I}dentification of {SLC}20{A}1 and {SLC}15{A}4 among other
genes as potential risk factors for combined pituitary
hormone deficiency.},
journal = {Genetics in medicine},
volume = {20},
number = {7},
issn = {1530-0366},
address = {Baltimore, Md.},
publisher = {Lippincott, Williams $\&$ Wilkins},
reportid = {DKFZ-2018-01337},
pages = {728 - 736},
year = {2018},
abstract = {Combined pituitary hormone deficiency (CPHD) is
characterized by a malformed or underdeveloped pituitary
gland resulting in an impaired pituitary hormone secretion.
Several transcription factors have been described in its
etiology, but defects in known genes account for only a
small proportion of cases.To identify novel genetic causes
for congenital hypopituitarism, we performed
exome-sequencing studies on 10 patients with CPHD and their
unaffected parents. Two candidate genes were sequenced in
further 200 patients. Genotype data of known hypopituitary
genes are reviewed.We discovered 51 likely damaging variants
in 38 genes; 12 of the 51 variants represent de novo events
$(24\%);$ 11 of the 38 genes $(29\%)$ were present in the
E12.5/E14.5 pituitary transcriptome. Targeted sequencing of
two candidate genes, SLC20A1 and SLC15A4, of the solute
carrier membrane transport protein family in 200 additional
patients demonstrated two further variants predicted as
damaging. We also found combinations of de novo
(SLC20A1/SLC15A4) and transmitted variants (GLI2/LHX3) in
the same individuals, leading to the full-blown CPHD
phenotype.These data expand the pituitary target genes
repertoire for diagnostics and further functional studies.
Exome sequencing has identified a combination of rare
variants in different genes that might explain incomplete
penetrance in CPHD.},
cin = {B080 / B240 / W110 / B050},
ddc = {570},
cid = {I:(DE-He78)B080-20160331 / I:(DE-He78)B240-20160331 /
I:(DE-He78)W110-20160331 / I:(DE-He78)B050-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29261175},
doi = {10.1038/gim.2017.165},
url = {https://inrepo02.dkfz.de/record/136899},
}