Missense mutations in <i>SLC25A1</i> are associated with congenital myasthenic syndrome type 23

Al‐Futaisi, Amna; Ahmad, Faraz; Al‐Kasbi, Ghalia; Al‐Thihli, Khalid; Koul, Roshan; Al‐Maawali, Almundher

doi:10.1111/cge.13678

Cited by 10 publications

(7 citation statements)

References 4 publications

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“…In terms of treatment, two other patients have shown functional benefits from treatment with acetylcholinesterase (AChE) inhibitors, whereas others did not benefit despite appropriate medication and dosing. One patient responded well to 3,4-diamino pyridine (DAP), consistent with presynaptic NMJ defects [ 8 , 9 ]. Patients with a mild phenotype and minimal symptoms may not require treatment with AChE inhibitors or 3,4-DAP [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Congenital Myasthenic Syndrome Associated With SLC25A1 Gene Variant: The First Reported Case in Saudi Arabia

Alzahrani¹,

Alghamdi²,

Alghamdi³

et al. 2023

Cureus

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We report the case of a two-year-old full-term girl of consanguineous Saudi parents, who had a history of poor sucking, hypotonia, and bilateral ptosis, as well as recurrent pediatric intensive care unit (PICU) admissions with apnea and global developmental delay and unremarkable family history. A genetic study was conducted and whole exome sequencing (WES) identified a likely pathogenic homozygous variant c.842C>T p.(Ala281Val) in the SLC25A1 gene. This finding is consistent with the genetic diagnosis of autosomal recessive combined D-2-and L-2-hydroxyglutaric aciduria (D/L-2-HGA). Genetic testing results suggested a diagnosis of congenital myasthenic syndrome (CMS) type 23 [Online Mendelian Inheritance in Man (OMIM) #618197]. CMS is a highly heterogeneous group of neuromuscular junction (NMJ) disorders clinically and genetically and compromises the safety margin required for reliable neuromuscular transmission. Fortunately, we suspected a CMS in our patient, and the initiation of management with pyridostigmine has substantially improved the patient's condition.

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Section: Discussionmentioning

confidence: 99%

Congenital Myasthenic Syndrome Associated With SLC25A1 Gene Variant: The First Reported Case in Saudi Arabia

Alzahrani¹,

Alghamdi²,

Alghamdi³

et al. 2023

Cureus

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“…Another four patients with the same missense variant in SLC25A1 were identified as having mild CMS with ID in 2019 [6]. In addition to the recurrent reported pathogenic variant (c.740G > A; p.R247Q), the other missense variant (c.205G > T; p. D69Y) was recently confirmed in three siblings with CMS [7].…”

Section: Introductionmentioning

confidence: 79%

“…This protein belongs to the SLC25 family of mitochondrial carriers (MCs), which are mainly localized in the inner mitochondrial membrane and are responsible for the trafficking of a variety of metabolites [9,10]. The locus of this gene (22q11.2) has also attracted some attention, as it is either translocated or amplified in some tumours [5] Reference [6] Reference [7] Our case Reference [5] Reference [6] Reference [7] Our case and deleted in DiGeorge syndrome and possibly schizophrenia [11,12]. Since 2013, SLC25A1 has been reported to be linked to human diseases.…”

Section: Discussionmentioning

confidence: 99%

A case report of an intermediate phenotype between congenital myasthenic syndrome and D-2- and L-2-hydroxyglutaric aciduria due to novel SLC25A1 variants

Zhang

et al. 2020

BMC Neurol

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Background: Variants in the SLC25A1 gene are associated with a severe neurometabolic disease, D-2-and L-2hydroxyglutaric aciduria (D/L-2-HGA). A report in 2014 presented the first account of congenital myasthenic syndrome (CMS) with mild intellectual disability (ID) caused by SLC25A1. To date, only two missense variants in SLC25A1 have been linked to CMS. Case presentations: A Chinese boy presented fatigable muscular weakness, myasthenic crisis, epilepsy and developmental delay along with mild elevation of urinary 2-ketoglutarate (2-KG) and lactic acid levels. He showed a partial response to pyridostigmine. Genetic analysis using trio whole-exome sequencing (WES), Sanger sequencing, and cosegregation analyses revealed two novel pathogenic variants of SLC25A1 (c.628C > T, p.R210X; c.145G > A, p.V49M). Conclusions: We report a boy who carries novel compound heterozygous variants of SLC25A1 and presents a phenotype intermediate between CMS and D/L-2-HGA. This case expands the range of known phenotypes and genotypes associated with SLC25A1.

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“…SLC25A1 -CMS has been reported in 19 patients in 10 pedigrees since 2014 [ 417 , 418 , 419 , 420 , 421 ]. Limb myasthenia and palpebral ptosis are shared features.…”

Section: Thirty-five Genes In 14 Groups Of Cmsmentioning

confidence: 99%

Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes—A Comprehensive Review

Ohno

Ohkawara

Shen

et al. 2023

IJMS

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Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders characterized by impaired neuromuscular signal transmission due to germline pathogenic variants in genes expressed at the neuromuscular junction (NMJ). A total of 35 genes have been reported in CMS (AGRN, ALG14, ALG2, CHAT, CHD8, CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, COL13A1, COLQ, DOK7, DPAGT1, GFPT1, GMPPB, LAMA5, LAMB2, LRP4, MUSK, MYO9A, PLEC, PREPL, PURA, RAPSN, RPH3A, SCN4A, SLC18A3, SLC25A1, SLC5A7, SNAP25, SYT2, TOR1AIP1, UNC13A, VAMP1). The 35 genes can be classified into 14 groups according to the pathomechanical, clinical, and therapeutic features of CMS patients. Measurement of compound muscle action potentials elicited by repetitive nerve stimulation is required to diagnose CMS. Clinical and electrophysiological features are not sufficient to identify a defective molecule, and genetic studies are always required for accurate diagnosis. From a pharmacological point of view, cholinesterase inhibitors are effective in most groups of CMS, but are contraindicated in some groups of CMS. Similarly, ephedrine, salbutamol (albuterol), amifampridine are effective in most but not all groups of CMS. This review extensively covers pathomechanical and clinical features of CMS by citing 442 relevant articles.

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Missense mutations in SLC25A1 are associated with congenital myasthenic syndrome type 23

Cited by 10 publications

References 4 publications

Congenital Myasthenic Syndrome Associated With SLC25A1 Gene Variant: The First Reported Case in Saudi Arabia

Congenital Myasthenic Syndrome Associated With SLC25A1 Gene Variant: The First Reported Case in Saudi Arabia

A case report of an intermediate phenotype between congenital myasthenic syndrome and D-2- and L-2-hydroxyglutaric aciduria due to novel SLC25A1 variants

Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes—A Comprehensive Review

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