Biallelic P4HTM variants associated with HIDEA syndrome and mitochondrial respiratory chain complex I deficiency.
TLDR
A patient with profound congenital hypotonia, central hypoventilation, poor visual behavior with retinal hypopigmentation, and significantly decreased mitochondrial respiratory chain complex I activity in muscle, who died at 7 months of age having made minimal developmental progress was reported in this article.Abstract:
We report a patient with profound congenital hypotonia, central hypoventilation, poor visual behaviour with retinal hypopigmentation, and significantly decreased mitochondrial respiratory chain complex I activity in muscle, who died at 7 months of age having made minimal developmental progress. Biallelic predicted truncating P4HTM variants were identified following trio whole-genome sequencing, consistent with a diagnosis of hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy and eye abnormalities (HIDEA) syndrome. Very few patients with HIDEA syndrome have been reported previously and mitochondrial abnormalities were observed in three of four previous cases who had a muscle biopsy, suggesting the possibility that HIDEA syndrome represents a primary mitochondrial disorder. P4HTM encodes a transmembrane prolyl 4-hydroxylase with putative targets including hypoxia inducible factors, RNA polymerase II and activating transcription factor 4, which has been implicated in the integrated stress response observed in cell and animal models of mitochondrial disease, and may explain the mitochondrial dysfunction observed in HIDEA syndrome.read more
Citations
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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
Minna Kraatari-Tiri,Leila Soikkonen,Matti Myllykoski,Yalda Jamshidi,E Ghayour Karimiani,Jonna Komulainen-Ebrahim,Hanna Kallankari,Cyril Mignot,Boris Keren,Marie-Christine Nougues,Zahra Alsahlawi,Antonio Romito,Javier Martini,Mehran Beiraghi Toosi,Christopher Carroll,Kornélia Tripolszki,Peter Bauer,Johanna Uusimaa,Aida M. Bertoli-Avella,Peppi Koivunen,Elisa Rahikkala +20 more
TL;DR: Six new patients with HIDEA syndrome are reported, caused by five different biallelic P4HTM variants, including three novel variants, which expand knowledge of the genotypic and phenotypic spectrum of the disease.
Journal ArticleDOI
HIDEA syndrome: A rare cause of congenital hypoventilation in a premature infant
Alison Lim,Pih Lin Tan,Nirmal Kavalloor Visruthan,Nikki Wen Yan Fong,Guadalupe Viegelmann,Yi Hua Tan +5 more
TL;DR: A premature patient who required extensive work up for his hypoventilation with a diagnosis of HIDEA syndrome is described.
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Fond farewell to clinical utility gene cards.
Journal ArticleDOI
HIDEA syndrome: A new case report highlighting similarities with ROHHAD syndrome
Julie Harvengt,Aimé Lumaka,Corinne Fasquelle,Jean-Hubert Caberg,Maha Mastouri,A. H. Janssen,Leonor Palmeira,Vincent Bours +7 more
TL;DR: The first patient identified with HIDEA syndrome from our ROHHAD cohort was a 21-month-old girl who had a history of severe respiratory infections requiring intensive care, hypotonia, abnormal eye movements, and rapid weight gain this article .
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