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
Year: 2022
Type: article
Abstract: 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.
Source: Clinical Genetics
DOI: 10.1111/cge.14203
Authors: Minna Kraatari‐Tiri, Leila Soikkonen, Matti Myllykoski, Yalda Jamshidi, Ehsan G. Karimiani, Jonna Komulainen‐Ebrahim, Hanna Kallankari, Cyril Mignot, Christel Depienne, Boris Keren, Marie‐Christine Nougues, Zahra Alsahlawi, Antonio Romito, Javier Martini, Mehran B. Toosi, Christopher J. Carroll, Kornelia Tripolszki, Peter Bauer, Johanna Uusimaa, Aida M. Bertoli‐Avella, Peppi Koivunen, Elisa Rahikkala
Institutions: Oulu University Hospital, University of Oulu, University of Bergen, University of London, St George's, University of London, Mashhad University of Medical Sciences, Sorbonne Université, Hôpital Armand-Trousseau, Pitié-Salpêtrière Hospital, Assistance Publique – Hôpitaux de Paris, Salmaniya Medical Complex, Centogene (Germany)
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,600
Funder: Academy of Finland
OpenAlex ID: W4288903005