University of Oulu

Kraatari-Tiri, M, Soikkonen, L, Myllykoski, M, et al. HIDEA syndrome is caused by biallelic, pathogenic, rare or founder P4HTM variants impacting the active site or the overall stability of the P4H-TM protein. Clinical Genetics. 2022; 102( 5): 444- 450. doi:10.1111/cge.14203

HIDEA syndrome is caused by biallelic, pathogenic, rare or founder P4HTM variants impacting the active site or the overall stability of the P4H-TM protein

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Author: Kraatari-Tiri, Minna1,2; Soikkonen, Leila1,2; Myllykoski, Matti3;
Organizations: 1PEDEGO Research Unit, University of Oulu, Oulu, Finland
2Department of Clinical Genetics and Medical Research Center, Oulu University Hospital, Oulu, Finland
3Department of Biomedicine, University of Bergen, Bergen, Norway
4Genetics Section, Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, UK
5Department of Genetics, Next Generation Polyclinic, Mashhad, Iran
6Department of Children and Adolescents and Medical Research Center, Oulu University Hospital, Oulu, Finland
7APHP.Sorbonne Université, Département de Génétique, Hôpital Armand Trousseau and Groupe Hospitalier Pitié-Salpêtrière, Centre de Référence Déficiences Intellectuelles de Causes Rares, Paris, France
8Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, APHP.Sorbonne Université, Paris, France
9Département de Neuropédiatrie, APHP.Sorbonne Université, Hôpital Trousseau, Trousseau, France
10Department of Pediatrics, Salmaniya Medical Complex, Kingdom of Bahrain, Bahrain
11Department of Medical Reporting and Genomics, Centogene GmbH, Rostock, Germany
12Department of Pediatrics, School of medicine, Mashhad University of Medical Sciences, Mashhad, Iran
13Biocenter Oulu, University of Oulu, Oulu, Finland
14Faculty of Biochemistry and Molecular Medicine, Oulu Centre for Cell-Matrix Research, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
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Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2022-12-09


HIDEA syndrome is caused by biallelic pathogenic variants in P4HTM. The phenotype is characterized by muscular and central hypotonia, hypoventilation including obstructive and central sleep apneas, intellectual disability, dysautonomia, epilepsy, eye abnormalities, and an increased tendency to develop respiratory distress during pneumonia. Here, we report six new patients with HIDEA syndrome caused by five different biallelic P4HTM variants, including three novel variants. We describe two Finnish enriched pathogenic P4HTM variants and demonstrate that these variants are embedded within founder haplotypes. We review the clinical data from all previously published patients with HIDEA and characterize all reported P4HTM pathogenic variants associated with HIDEA in silico. All known pathogenic variants in P4HTM result in either premature stop codons, an intragenic deletion, or amino acid changes that impact the active site or the overall stability of P4H-TM protein. In all cases, normal P4H-TM enzyme function is expected to be lost or severely decreased. This report expands knowledge of the genotypic and phenotypic spectrum of the disease.

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Series: Clinical genetics
ISSN: 0009-9163
ISSN-E: 1399-0004
ISSN-L: 0009-9163
Volume: 102
Issue: 5
Pages: 444 - 450
DOI: 10.1111/cge.14203
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: Academy of Finland, Grant/Award Number: 338446.
Academy of Finland Grant Number: 338446
Detailed Information: 338446 (Academy of Finland Funding decision)
Copyright information: © 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.