Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2.
Kallmann syndrome combines anosmia, related to defective olfactory bulb morphogenesis, and hypogonadism due to gonadotropin-releasing hormone deficiency. Loss-of-function mutations in KAL1 and FGFR1 underlie the X chromosome-linked form and an autosomal dominant form of the disease, respectively. Mu...
Main Authors: | , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2006-10-01
|
Series: | PLoS Genetics |
Online Access: | http://europepmc.org/articles/PMC1617130?pdf=render |
id |
doaj-50d8b53524c94d4aa60add58764d427e |
---|---|
record_format |
Article |
spelling |
doaj-50d8b53524c94d4aa60add58764d427e2020-11-24T21:44:21ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042006-10-01210e17510.1371/journal.pgen.0020175Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2.Catherine DodéLuis TeixeiraJacqueline LevilliersCorinne FouveautPhilippe BouchardMarie-Laure KottlerJames LespinasseAnne Lienhardt-RoussieMichèle MathieuAlexandre MoermanGraeme MorganArnaud MuratJean-Edmont ToublancSlawomir WolczynskiMarc DelpechChristine PetitJacques YoungJean-Pierre HardelinKallmann syndrome combines anosmia, related to defective olfactory bulb morphogenesis, and hypogonadism due to gonadotropin-releasing hormone deficiency. Loss-of-function mutations in KAL1 and FGFR1 underlie the X chromosome-linked form and an autosomal dominant form of the disease, respectively. Mutations in these genes, however, only account for approximately 20% of all Kallmann syndrome cases. In a cohort of 192 patients we took a candidate gene strategy and identified ten and four different point mutations in the genes encoding the G protein-coupled prokineticin receptor-2 (PROKR2) and one of its ligands, prokineticin-2 (PROK2), respectively. The mutations in PROK2 were detected in the heterozygous state, whereas PROKR2 mutations were found in the heterozygous, homozygous, or compound heterozygous state. In addition, one of the patients heterozygous for a PROKR2 mutation was also carrying a missense mutation in KAL1, thus indicating a possible digenic inheritance of the disease in this individual. These findings reveal that insufficient prokineticin-signaling through PROKR2 leads to abnormal development of the olfactory system and reproductive axis in man. They also shed new light on the complex genetic transmission of Kallmann syndrome.http://europepmc.org/articles/PMC1617130?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Catherine Dodé Luis Teixeira Jacqueline Levilliers Corinne Fouveaut Philippe Bouchard Marie-Laure Kottler James Lespinasse Anne Lienhardt-Roussie Michèle Mathieu Alexandre Moerman Graeme Morgan Arnaud Murat Jean-Edmont Toublanc Slawomir Wolczynski Marc Delpech Christine Petit Jacques Young Jean-Pierre Hardelin |
spellingShingle |
Catherine Dodé Luis Teixeira Jacqueline Levilliers Corinne Fouveaut Philippe Bouchard Marie-Laure Kottler James Lespinasse Anne Lienhardt-Roussie Michèle Mathieu Alexandre Moerman Graeme Morgan Arnaud Murat Jean-Edmont Toublanc Slawomir Wolczynski Marc Delpech Christine Petit Jacques Young Jean-Pierre Hardelin Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genetics |
author_facet |
Catherine Dodé Luis Teixeira Jacqueline Levilliers Corinne Fouveaut Philippe Bouchard Marie-Laure Kottler James Lespinasse Anne Lienhardt-Roussie Michèle Mathieu Alexandre Moerman Graeme Morgan Arnaud Murat Jean-Edmont Toublanc Slawomir Wolczynski Marc Delpech Christine Petit Jacques Young Jean-Pierre Hardelin |
author_sort |
Catherine Dodé |
title |
Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. |
title_short |
Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. |
title_full |
Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. |
title_fullStr |
Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. |
title_full_unstemmed |
Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. |
title_sort |
kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2006-10-01 |
description |
Kallmann syndrome combines anosmia, related to defective olfactory bulb morphogenesis, and hypogonadism due to gonadotropin-releasing hormone deficiency. Loss-of-function mutations in KAL1 and FGFR1 underlie the X chromosome-linked form and an autosomal dominant form of the disease, respectively. Mutations in these genes, however, only account for approximately 20% of all Kallmann syndrome cases. In a cohort of 192 patients we took a candidate gene strategy and identified ten and four different point mutations in the genes encoding the G protein-coupled prokineticin receptor-2 (PROKR2) and one of its ligands, prokineticin-2 (PROK2), respectively. The mutations in PROK2 were detected in the heterozygous state, whereas PROKR2 mutations were found in the heterozygous, homozygous, or compound heterozygous state. In addition, one of the patients heterozygous for a PROKR2 mutation was also carrying a missense mutation in KAL1, thus indicating a possible digenic inheritance of the disease in this individual. These findings reveal that insufficient prokineticin-signaling through PROKR2 leads to abnormal development of the olfactory system and reproductive axis in man. They also shed new light on the complex genetic transmission of Kallmann syndrome. |
url |
http://europepmc.org/articles/PMC1617130?pdf=render |
work_keys_str_mv |
AT catherinedode kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT luisteixeira kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT jacquelinelevilliers kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT corinnefouveaut kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT philippebouchard kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT marielaurekottler kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT jameslespinasse kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT annelienhardtroussie kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT michelemathieu kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT alexandremoerman kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT graememorgan kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT arnaudmurat kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT jeanedmonttoublanc kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT slawomirwolczynski kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT marcdelpech kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT christinepetit kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT jacquesyoung kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 AT jeanpierrehardelin kallmannsyndromemutationsinthegenesencodingprokineticin2andprokineticinreceptor2 |
_version_ |
1725911002201980928 |