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PHIP-associated Chung-Jansen syndrome: Report of 23 new individuals
In 2016 and 2018, Chung, Jansen and others described a new syndrome caused by haploinsufficiency of PHIP (pleckstrin homology domain interacting protein, OMIM *612,870) and mainly characterized by developmental delay (DD), learning difficulties/intellectual disability (ID), behavioral abnormalities,...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886139/ https://www.ncbi.nlm.nih.gov/pubmed/36726590 http://dx.doi.org/10.3389/fcell.2022.1020609 |
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author | Kampmeier, Antje Leitão, Elsa Parenti, Ilaria Beygo, Jasmin Depienne, Christel Bramswig, Nuria C Hsieh, Tzung-Chien Afenjar, Alexandra Beck-Wödl, Stefanie Grasshoff, Ute Haack, Tobias B Bijlsma, Emilia K Ruivenkamp, Claudia Lausberg, Eva Elbracht, Miriam Haanpää, Maria K Koillinen, Hannele Heinrich, Uwe Rost, Imma Jamra, Rami Abou Popp, Denny Koch-Hogrebe, Margarete Rostasy, Kevin López-González, Vanesa Sanchez-Soler, María José Macedo, Catarina Schmetz, Ariane Steinborn, Carmen Weidensee, Sabine Lesmann, Hellen Marbach, Felix Caro, Pilar Schaaf, Christian P. Krawitz, Peter Wieczorek, Dagmar Kaiser, Frank J Kuechler, Alma |
author_facet | Kampmeier, Antje Leitão, Elsa Parenti, Ilaria Beygo, Jasmin Depienne, Christel Bramswig, Nuria C Hsieh, Tzung-Chien Afenjar, Alexandra Beck-Wödl, Stefanie Grasshoff, Ute Haack, Tobias B Bijlsma, Emilia K Ruivenkamp, Claudia Lausberg, Eva Elbracht, Miriam Haanpää, Maria K Koillinen, Hannele Heinrich, Uwe Rost, Imma Jamra, Rami Abou Popp, Denny Koch-Hogrebe, Margarete Rostasy, Kevin López-González, Vanesa Sanchez-Soler, María José Macedo, Catarina Schmetz, Ariane Steinborn, Carmen Weidensee, Sabine Lesmann, Hellen Marbach, Felix Caro, Pilar Schaaf, Christian P. Krawitz, Peter Wieczorek, Dagmar Kaiser, Frank J Kuechler, Alma |
author_sort | Kampmeier, Antje |
collection | PubMed |
description | In 2016 and 2018, Chung, Jansen and others described a new syndrome caused by haploinsufficiency of PHIP (pleckstrin homology domain interacting protein, OMIM *612,870) and mainly characterized by developmental delay (DD), learning difficulties/intellectual disability (ID), behavioral abnormalities, facial dysmorphism and obesity (CHUJANS, OMIM #617991). So far, PHIP alterations appear to be a rare cause of DD/ID. “Omics” technologies such as exome sequencing or array analyses have led to the identification of distinct types of alterations of PHIP, including, truncating variants, missense substitutions, splice variants and large deletions encompassing portions of the gene or the entire gene as well as adjacent genomic regions. We collected clinical and genetic data of 23 individuals with PHIP-associated Chung-Jansen syndrome (CHUJANS) from all over Europe. Follow-up investigations (e.g. Sanger sequencing, qPCR or Fluorescence-in-situ-Hybridization) and segregation analysis showed either de novo occurrence or inheritance from an also (mildly) affected parent. In accordance with previously described patients, almost all individuals reported here show developmental delay (22/23), learning disability or ID (22/23), behavioral abnormalities (20/23), weight problems (13/23) and characteristic craniofacial features (i.e. large ears/earlobes, prominent eyebrows, anteverted nares and long philtrum (23/23)). To further investigate the facial gestalt of individuals with CHUJANS, we performed facial analysis using the GestaltMatcher approach. By this, we could establish that PHIP patients are indistinguishable based on the type of PHIP alteration (e.g. missense, loss-of-function, splice site) but show a significant difference to the average face of healthy individuals as well as to individuals with Prader-Willi syndrome (PWS, OMIM #176270) or with a CUL4B-alteration (Intellectual developmental disorder, X-linked, syndromic, Cabezas type, OMIM #300354). Our findings expand the mutational and clinical spectrum of CHUJANS. We discuss the molecular and clinical features in comparison to the published individuals. The fact that some variants were inherited from a mildly affected parent further illustrates the variability of the associated phenotype and outlines the importance of a thorough clinical evaluation combined with genetic analyses for accurate diagnosis and counselling. |
format | Online Article Text |
id | pubmed-9886139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98861392023-01-31 PHIP-associated Chung-Jansen syndrome: Report of 23 new individuals Kampmeier, Antje Leitão, Elsa Parenti, Ilaria Beygo, Jasmin Depienne, Christel Bramswig, Nuria C Hsieh, Tzung-Chien Afenjar, Alexandra Beck-Wödl, Stefanie Grasshoff, Ute Haack, Tobias B Bijlsma, Emilia K Ruivenkamp, Claudia Lausberg, Eva Elbracht, Miriam Haanpää, Maria K Koillinen, Hannele Heinrich, Uwe Rost, Imma Jamra, Rami Abou Popp, Denny Koch-Hogrebe, Margarete Rostasy, Kevin López-González, Vanesa Sanchez-Soler, María José Macedo, Catarina Schmetz, Ariane Steinborn, Carmen Weidensee, Sabine Lesmann, Hellen Marbach, Felix Caro, Pilar Schaaf, Christian P. Krawitz, Peter Wieczorek, Dagmar Kaiser, Frank J Kuechler, Alma Front Cell Dev Biol Cell and Developmental Biology In 2016 and 2018, Chung, Jansen and others described a new syndrome caused by haploinsufficiency of PHIP (pleckstrin homology domain interacting protein, OMIM *612,870) and mainly characterized by developmental delay (DD), learning difficulties/intellectual disability (ID), behavioral abnormalities, facial dysmorphism and obesity (CHUJANS, OMIM #617991). So far, PHIP alterations appear to be a rare cause of DD/ID. “Omics” technologies such as exome sequencing or array analyses have led to the identification of distinct types of alterations of PHIP, including, truncating variants, missense substitutions, splice variants and large deletions encompassing portions of the gene or the entire gene as well as adjacent genomic regions. We collected clinical and genetic data of 23 individuals with PHIP-associated Chung-Jansen syndrome (CHUJANS) from all over Europe. Follow-up investigations (e.g. Sanger sequencing, qPCR or Fluorescence-in-situ-Hybridization) and segregation analysis showed either de novo occurrence or inheritance from an also (mildly) affected parent. In accordance with previously described patients, almost all individuals reported here show developmental delay (22/23), learning disability or ID (22/23), behavioral abnormalities (20/23), weight problems (13/23) and characteristic craniofacial features (i.e. large ears/earlobes, prominent eyebrows, anteverted nares and long philtrum (23/23)). To further investigate the facial gestalt of individuals with CHUJANS, we performed facial analysis using the GestaltMatcher approach. By this, we could establish that PHIP patients are indistinguishable based on the type of PHIP alteration (e.g. missense, loss-of-function, splice site) but show a significant difference to the average face of healthy individuals as well as to individuals with Prader-Willi syndrome (PWS, OMIM #176270) or with a CUL4B-alteration (Intellectual developmental disorder, X-linked, syndromic, Cabezas type, OMIM #300354). Our findings expand the mutational and clinical spectrum of CHUJANS. We discuss the molecular and clinical features in comparison to the published individuals. The fact that some variants were inherited from a mildly affected parent further illustrates the variability of the associated phenotype and outlines the importance of a thorough clinical evaluation combined with genetic analyses for accurate diagnosis and counselling. Frontiers Media S.A. 2023-01-16 /pmc/articles/PMC9886139/ /pubmed/36726590 http://dx.doi.org/10.3389/fcell.2022.1020609 Text en Copyright © 2023 Kampmeier, Leitão, Parenti, Beygo, Depienne, Bramswig, Hsieh, Afenjar, Beck-Wödl, Grasshoff, Haack, Bijlsma, Ruivenkamp, Lausberg, Elbracht, Haanpää, Koillinen, Heinrich, Rost, Jamra, Popp, Koch-Hogrebe, Rostasy, López-González, Sanchez-Soler, Macedo, Schmetz, Steinborn, Weidensee, Lesmann, Marbach, Caro, Schaaf, Krawitz, Wieczorek, Kaiser and Kuechler. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Kampmeier, Antje Leitão, Elsa Parenti, Ilaria Beygo, Jasmin Depienne, Christel Bramswig, Nuria C Hsieh, Tzung-Chien Afenjar, Alexandra Beck-Wödl, Stefanie Grasshoff, Ute Haack, Tobias B Bijlsma, Emilia K Ruivenkamp, Claudia Lausberg, Eva Elbracht, Miriam Haanpää, Maria K Koillinen, Hannele Heinrich, Uwe Rost, Imma Jamra, Rami Abou Popp, Denny Koch-Hogrebe, Margarete Rostasy, Kevin López-González, Vanesa Sanchez-Soler, María José Macedo, Catarina Schmetz, Ariane Steinborn, Carmen Weidensee, Sabine Lesmann, Hellen Marbach, Felix Caro, Pilar Schaaf, Christian P. Krawitz, Peter Wieczorek, Dagmar Kaiser, Frank J Kuechler, Alma PHIP-associated Chung-Jansen syndrome: Report of 23 new individuals |
title |
PHIP-associated Chung-Jansen syndrome: Report of 23 new individuals |
title_full |
PHIP-associated Chung-Jansen syndrome: Report of 23 new individuals |
title_fullStr |
PHIP-associated Chung-Jansen syndrome: Report of 23 new individuals |
title_full_unstemmed |
PHIP-associated Chung-Jansen syndrome: Report of 23 new individuals |
title_short |
PHIP-associated Chung-Jansen syndrome: Report of 23 new individuals |
title_sort | phip-associated chung-jansen syndrome: report of 23 new individuals |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886139/ https://www.ncbi.nlm.nih.gov/pubmed/36726590 http://dx.doi.org/10.3389/fcell.2022.1020609 |
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