Clinical and neuropathological features of X-linked spinal muscular atrophy (SMAX2) associated with a novel mutation in the UBA1 gene

Dlamini, Nomazulu; Josifova, Dragana; Paine, Simon; Wraige, Elizabeth; Pitt, Matthew; Murphy, Anna V.; King, Andrew; Buk, Stefan; Smith, Frances J.D.; Abbs, Stephen; Sewry, Caroline A.; Jacques, Thomas S.; Jungbluth, Heinz

doi:10.1016/j.nmd.2013.02.001

Cited by 46 publications

(54 citation statements)

References 31 publications

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“…Indeed, fractures presenting in the pre-or perinatal period seem to be the most characteristic (but not mandatory) symptom of SMAX2. In the family reported by Greenberg et al, three of the four patients had femur and/or humerus fractures [10], while no fractures were observed in a patient described by Dlamini et al [5]. Multiple contractures and bone fractures were also noted in SMN1-dependent SMA with a retained single copy of the SMN2 gene [11] and in severe forms of nemaline myopathy [12][13][14].…”

Section: Discussionmentioning

confidence: 91%

“…While there are several clinical reports of children with severe spinal muscular atrophy associated with arthrogryposis and bone fractures [7][8][9], only 6 families with SMAX2 have been verified at the molecular level [1,5]. Of these only two are described in detail [5,10] (Table 1), therefore we decided to present the clinical history of our patient.…”

Section: Discussionmentioning

confidence: 99%

“…Of these only two are described in detail [5,10] (Table 1), therefore we decided to present the clinical history of our patient.…”

Section: Discussionmentioning

confidence: 99%

“…At this time the child was very weak, with marked shortness of breath, and invasive investigations (EMG, muscle biopsy) were therefore not performed. However, on the basis of clinical presentation a presumptive diagnosis of SMAX2 was made, and blood for Described by Greenberg et al [10] Greenberg et al [10] Greenberg et al [10] Greenberg et al [10] Dlamini et al [5] Our patient genetic testing was collected. The parents provided written informed consent for genetic analysis.…”

Section: Laboratory Investigationsmentioning

confidence: 99%

“…In 2008 Ramser et al determined that mutations of the UBA1 gene, located within this region of chromosome X, are responsible for SMAX2. To date, only four variants of the UBA1 gene have been reported in six SMAX2 families, all of them localized in exon 15 [1,5].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

X-linked spinal muscular atrophy (SMAX2) caused by de novo c.1731C>T substitution in the UBA1 gene

Jędrzejowska

Jakubowska-Pietkiewicz

Kostera‐Pruszczyk

2015

Neuromuscular Disorders

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

“…Of these only two are described in detail [5,10] (Table 1), therefore we decided to present the clinical history of our patient.…”

Section: Discussionmentioning

confidence: 99%

Section: Laboratory Investigationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

X-linked spinal muscular atrophy (SMAX2) caused by de novo c.1731C>T substitution in the UBA1 gene

Jędrzejowska

Jakubowska-Pietkiewicz

Kostera‐Pruszczyk

2015

Neuromuscular Disorders

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Review of X‐linked syndromes with arthrogryposis or early contractures—aid to diagnosis and pathway identification

Hunter

Kiefer

Balak

et al. 2015

American J of Med Genetics Pt A

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The following is a review of 50 X-linked syndromes and conditions associated with either arthrogryposis or other types of early contractures. These entities are categorized as those with known responsible gene mutations, those which are definitely X-linked, but the responsible gene has not been identified, and those suspected from family history to be X-linked. Several important ontology pathways for known disease genes have been identified and are discussed in relevance to clinical characteristics. Tables are included which help to identify distinguishing clinical features of each of the conditions.

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A novel Xp11.22–22.33 deletion suggesting a possible mechanism of congenital cervical spinal muscular atrophy

Liu

Wang

et al. 2021

Molec Gen & Gen Med

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Background Congenital cervical spinal muscular atrophy (CCSMA) is a rare, nonprogressive, neurogenic disorder characterized by symmetric arthrogryposis and motor deficits mainly confined to upper extremities. Since its first proposal by Darwish et al. 39 years ago, only few cases have ever been reported. Vascular insult to the anterior horn of cervical spinal cord during fetal development was speculated to be the cause, however, the exact pathogenesis is still not well understood. Methods In this study, whole‐exome sequencing (WES) and copy number variation (CNV) analysis were conducted on a definitive CCSMA patient, confirmed by the clinical manifestations and other supplementary examinations. Results On physical examination, the patient was mainly characterized by symmetric, congenital, nonprogressive contractures, hypotonia, and muscle weakness mainly confined to the upper limbs, which were further supported by MRI and electromyography. Neuromuscular biopsy of the deltoid muscle demonstrated the type 1 myofiber predominance without any infiltration of inflammatory cells. The WES and CNV analysis unveiled a de novo Xp11.22–22.33 deletion. On further examination of the genes contained within this segment, we recognize UBA1 gene as the most likely pathogenic gene. Ubiquitin‐like modifier activating enzyme 1 is encoded by UBA1 gene (MIM 314370) located in Xp11.3 and is a critical protein that plays a vital role in ubiquitin‐proteasome system and autophagy. It is well documented that UBA1 gene mutation causes X‐linked infantile spinal muscular atrophy (XL‐SMA), which manifests phenotypes of arthrogryposis, hypotonia, and myopathic face. Type 2 XL‐SMA, which follows a nonprogressive and nonlethal course is very similar to the presentations of CCSMA. Conclusion The phenotypic similarities between this CCSMA case and XL‐SMA prompt us to hypothesize a possible connection between UBA1 gene deficit and the pathogenesis of CCSMA. Our study is the first to demonstrate that CCSMA might have a genetic etiology, thus, expanding our insights into the underlying cause of CCSMA.

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Clinical and neuropathological features of X-linked spinal muscular atrophy (SMAX2) associated with a novel mutation in the UBA1 gene

Cited by 46 publications

References 31 publications

X-linked spinal muscular atrophy (SMAX2) caused by de novo c.1731C>T substitution in the UBA1 gene

X-linked spinal muscular atrophy (SMAX2) caused by de novo c.1731C>T substitution in the UBA1 gene

Review of X‐linked syndromes with arthrogryposis or early contractures—aid to diagnosis and pathway identification

A novel Xp11.22–22.33 deletion suggesting a possible mechanism of congenital cervical spinal muscular atrophy

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