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CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy

The relationship between congenital defects of the brain and facial anomalies was proven. The Hedgehog signaling pathway plays a fundamental role in normal craniofacial development in humans. Mutations in the sonic hedgehog (SHH) signaling gene CDON have been recently reported in patients with holop...

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Autores principales: Obara-Moszyńska, Monika, Budny, Bartłomiej, Kałużna, Małgorzata, Zawadzka, Katarzyna, Jamsheer, Aleksander, Rohde, Anna, Ruchała, Marek, Ziemnicka, Katarzyna, Niedziela, Marek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571149/
https://www.ncbi.nlm.nih.gov/pubmed/34235642
http://dx.doi.org/10.1007/s13353-021-00649-w
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author Obara-Moszyńska, Monika
Budny, Bartłomiej
Kałużna, Małgorzata
Zawadzka, Katarzyna
Jamsheer, Aleksander
Rohde, Anna
Ruchała, Marek
Ziemnicka, Katarzyna
Niedziela, Marek
author_facet Obara-Moszyńska, Monika
Budny, Bartłomiej
Kałużna, Małgorzata
Zawadzka, Katarzyna
Jamsheer, Aleksander
Rohde, Anna
Ruchała, Marek
Ziemnicka, Katarzyna
Niedziela, Marek
author_sort Obara-Moszyńska, Monika
collection PubMed
description The relationship between congenital defects of the brain and facial anomalies was proven. The Hedgehog signaling pathway plays a fundamental role in normal craniofacial development in humans. Mutations in the sonic hedgehog (SHH) signaling gene CDON have been recently reported in patients with holoprosencephaly and with pituitary stalk interruption syndrome (PSIS). This study’s aim was an elucidation of an 18-year-old patient presenting PSIS, multiple pituitary hormone deficiency, and congenital unilateral facial and abducens nerve palsy. Additionally, bilateral sensorineural hearing loss, dominating at the right site, was diagnosed. From the second year of life, growth deceleration was observed, and from the age of eight, anterior pituitary hormone deficiencies were gradually confirmed and substituted. At the MRI, characteristic triad for PSIS (anterior pituitary hypoplasia, interrupted pituitary stalk and ectopic posterior lobe) was diagnosed. We performed a comprehensive genomic screening, including microarrays for structural rearrangements and whole-exome sequencing for a monogenic defect. A novel heterozygous missense variant in the CDON gene (c.1814G > T; p.Gly605Val) was identified. The variant was inherited from the mother, who, besides short stature, did not show any disease symptoms. The variant was absent in control databases and 100 healthy subjects originating from the same population. We report a novel variant in the CDON gene associated with PSIS and congenital cranial nerve palsy. The variant revealed autosomal dominant inheritance with incomplete penetrance in concordance with previous studies reporting CDON defects.
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spelling pubmed-85711492021-11-08 CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy Obara-Moszyńska, Monika Budny, Bartłomiej Kałużna, Małgorzata Zawadzka, Katarzyna Jamsheer, Aleksander Rohde, Anna Ruchała, Marek Ziemnicka, Katarzyna Niedziela, Marek J Appl Genet Human Genetics • Original Paper The relationship between congenital defects of the brain and facial anomalies was proven. The Hedgehog signaling pathway plays a fundamental role in normal craniofacial development in humans. Mutations in the sonic hedgehog (SHH) signaling gene CDON have been recently reported in patients with holoprosencephaly and with pituitary stalk interruption syndrome (PSIS). This study’s aim was an elucidation of an 18-year-old patient presenting PSIS, multiple pituitary hormone deficiency, and congenital unilateral facial and abducens nerve palsy. Additionally, bilateral sensorineural hearing loss, dominating at the right site, was diagnosed. From the second year of life, growth deceleration was observed, and from the age of eight, anterior pituitary hormone deficiencies were gradually confirmed and substituted. At the MRI, characteristic triad for PSIS (anterior pituitary hypoplasia, interrupted pituitary stalk and ectopic posterior lobe) was diagnosed. We performed a comprehensive genomic screening, including microarrays for structural rearrangements and whole-exome sequencing for a monogenic defect. A novel heterozygous missense variant in the CDON gene (c.1814G > T; p.Gly605Val) was identified. The variant was inherited from the mother, who, besides short stature, did not show any disease symptoms. The variant was absent in control databases and 100 healthy subjects originating from the same population. We report a novel variant in the CDON gene associated with PSIS and congenital cranial nerve palsy. The variant revealed autosomal dominant inheritance with incomplete penetrance in concordance with previous studies reporting CDON defects. Springer Berlin Heidelberg 2021-07-08 2021 /pmc/articles/PMC8571149/ /pubmed/34235642 http://dx.doi.org/10.1007/s13353-021-00649-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Human Genetics • Original Paper
Obara-Moszyńska, Monika
Budny, Bartłomiej
Kałużna, Małgorzata
Zawadzka, Katarzyna
Jamsheer, Aleksander
Rohde, Anna
Ruchała, Marek
Ziemnicka, Katarzyna
Niedziela, Marek
CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy
title CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy
title_full CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy
title_fullStr CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy
title_full_unstemmed CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy
title_short CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy
title_sort cdon gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy
topic Human Genetics • Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571149/
https://www.ncbi.nlm.nih.gov/pubmed/34235642
http://dx.doi.org/10.1007/s13353-021-00649-w
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