Academic Journal

Megaconial congenital muscular dystrophy due to novel CHKB variants: a case report and literature review

التفاصيل البيبلوغرافية
العنوان: Megaconial congenital muscular dystrophy due to novel CHKB variants: a case report and literature review
المؤلفون: Magri, Francesca, Antognozzi, Sara, Ripolone, Michela, Zanotti, Simona, Napoli, Laura, Ciscato, Patrizia, Velardo, Daniele, Scuvera, Giulietta, Nicotra, Valeria, Giacobbe, Antonella, Milani, Donatella, Fortunato, Francesco, Garbellini, Manuela, Sciacco, Monica, Corti, Stefania, Comi, Giacomo Pietro, Ronchi, Dario
المساهمون: F. Magri, S. Antognozzi, M. Ripolone, S. Zanotti, L. Napoli, P. Ciscato, D. Velardo, G. Scuvera, V. Nicotra, A. Giacobbe, D. Milani, F. Fortunato, M. Garbellini, M. Sciacco, S. Corti, G.P. Comi, D. Ronchi
بيانات النشر: BMC
سنة النشر: 2022
المجموعة: The University of Milan: Archivio Istituzionale della Ricerca (AIR)
مصطلحات موضوعية: Choline kinase beta (CHKB), Enlarged mitochondria, Megaconial congenital muscular dystrophy, Mitochondrial dynamic, Child, Creatine Kinase, Human, Male, Muscle, Skeletal, Mutation, Nucleotide, Phosphatidylcholine, Phosphatidylethanolamine, RNA, Choline Kinase, Muscular Dystrophies, Settore MED/26 - Neurologia
الوصف: Background Choline kinase beta (CHKB) catalyzes the first step in the de novo biosynthesis of phosphatidyl choline and phosphatidylethanolamine via the Kennedy pathway. Derangement of this pathway might also influence the homeostasis of mitochondrial membranes. Autosomal recessive CHKB mutations cause a rare form of congenital muscular dystrophy known as megaconial congenital muscular dystrophy (MCMD). Case presentation We describe a novel proband presenting MCMD due to unpublished CHKB mutations. The patient is a 6-year-old boy who came to our attention for cognitive impairment and slowly progressive muscular weakness. He was the first son of non-consanguineous healthy parents from Sri Lanka. Neurological examination showed proximal weakness at four limbs, weak osteotendinous reflexes, Gowers' maneuver, and waddling gate. Creatine kinase levels were mildly increased. EMG and brain MRI were normal. Left quadriceps skeletal muscle biopsy showed a myopathic pattern with nuclear centralizations and connective tissue increase. Histological and histochemical staining suggested subsarcolemmal localization and dimensional increase of mitochondria. Ultrastructural analysis confirmed the presence of enlarged ("megaconial") mitochondria. Direct sequencing of CHKB identified two novel defects: the c.1060G > C (p.Gly354Arg) substitution and the c.448-56_29del intronic deletion, segregating from father and mother, respectively. Subcloning of RT-PCR amplicons from patient's muscle RNA showed that c.448-56_29del results in the partial retention (14 nucleotides) of intron 3, altering physiological splicing and transcript stability. Biochemical studies showed reduced levels of the mitochondrial fission factor DRP1 and the severe impairment of mitochondrial respiratory chain activity in patient's muscle compared to controls. Conclusions This report expands the molecular findings associated with MCMD and confirms the importance of considering CHKB variants in the differential diagnosis of patients presenting with muscular ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/36175989; info:eu-repo/semantics/altIdentifier/wos/WOS:000861902100001; volume:12; issue:1; firstpage:1; lastpage:9; numberofpages:9; journal:SKELETAL MUSCLE; https://hdl.handle.net/2434/944642; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85138957338
DOI: 10.1186/s13395-022-00306-8
الاتاحة: https://hdl.handle.net/2434/944642
https://doi.org/10.1186/s13395-022-00306-8
Rights: info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.C6B01DB9
قاعدة البيانات: BASE
الوصف
DOI:10.1186/s13395-022-00306-8