Novel copy number variation of COLQ gene in a Moroccan patient with congenital myasthenic syndrome: a case report and review of the literature

• Published in: BMC neurology Vol. 22; no. 1; pp. 1 - 292
• Main Authors: El Kadiri, Youssef, Ratbi, Ilham, Sefiani, Abdelaziz, Lyahyai, Jaber
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 05-08-2022; BioMed Central; BMC
• Subjects: Acetylcholinesterase; Age; Algorithms; Analysis; Care and treatment; Case Report; COLQ gene; Congenital defects; Congenital diseases; Congenital myasthenic syndrome; Congenital myasthenic syndromes; Copy number; Copy number variations; Diagnosis; Gene deletion; Genes; Genetic aspects; Genetic counseling; Genetic disorders; Genetic testing; Genetics; Genomics; Heredity; Kinases; Literature reviews; Medical genetics; Methods; Mutation; Myasthenia; Neuromuscular junctions; Next-generation sequencing; Novel CNV; Parents & parenting; Patients; Protein interaction; Protein-protein interaction; Protein-protein interactions; Proteins; Salbutamol; Visual field; Morocco
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-022-02822-y

Background Congenital myasthenic syndromes (CMSs) are rare genetic diseases due to abnormalities of the neuromuscular junction leading to permanent or transient muscle fatigability and weakness. To date, 32 genes were found to be involved in CMSs with autosomal dominant and/or recessive inheritance patterns. CMS with acetylcholinesterase deficiency, in particular, was determined to be due to biallelic mutations of COLQ gene with early-onset clinical signs. Here, we report clinical features and novel molecular findings of COLQ-related CMS in a Moroccan patient with a review of the literature for this rare form. Case presentation In this study, we report the case of a 28-month-old Moroccan female patient with hypotonia, associated to axial muscle weakness, global motor delay, bilateral ptosis, unilateral partial visual field deficiency with normal ocular motility, and fatigable muscle weakness. Clinical exome sequencing revealed a novel homozygous deletion of exon 13 in COLQ gene, NM_005677.4(COLQ):c.(814+1_815-1)_(954+1_955-1) del p.(Gly272Aspfs*11). This finding was subsequently confirmed by quantitative real-time PCR (qPCR) in the proband and her parents. In silico analysis of protein-protein interaction network by STRING tool revealed that 12 proteins are highly associated to COLQ with an elevated confidence score. Treatment with Salbutamol resulted in clear benefits and recovery. Conclusions This clinical observation illustrates the important place of next-generation sequencing in the precise molecular diagnosis of heterogeneous forms of CMS, the appropriate management and targeted treatment, and genetic counseling of families, with a better characterization of the mutational profile of this rare disease in the Moroccan population. Keywords: Congenital myasthenic syndrome, COLQ gene, Novel CNV, Protein-protein interaction, Case report