Refined genetic mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.3 and evidence of linkage disequilibrium in European families

Viollet, Louis; Zarhrate, Mohammed; Maystadt, Isabelle; Estournet-Mathiaut, Brigitte; Barois, A; Desguerre, Isabelle; Mayer, M.; Chabrol, B.; Leheup, Bruno; Cusin, Véronica; Villemeur, Thierry Billette de; Bonneau, Dominique; Saugier-Veber, Pascale; Villepin, A. Touzery-de; Delaubier, Anne; Kaplan, J.-C.; Jeanpierre, Marc; Feingold, J; Münnich, Arnold

doi:10.1038/sj.ejhg.5201177

Cited by 14 publications

(7 citation statements)

References 9 publications

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“…The compilation of clinical findings in our patients affirms that SMARD is a genetically heterogeneous disorder [Grohmann et al, 1999;Maystadt et al, 2004;Viollet et al, 2004], and the high proportion of non-SMARD1 patients among our study cohort led us to review the clinical details of all submissions we had received. In order to support the clinical geneticist in his/her decision to send out patient material for mutation screening, we searched for clinical features that might speak in favor or against the presence of an IGHMBP2 mutation ( Table 1).…”

Section: Patient Cohort Studymentioning

confidence: 63%

Clinical and mutational profile in spinal muscular atrophy with respiratory distress (SMARD): defining novel phenotypes through hierarchical cluster analysis

et al. 2007

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Autosomal recessive spinal muscular atrophy with respiratory distress (SMARD) is a heterogeneous disorder. Mutations in the immunoglobulin micro-binding protein gene (IGHMBP2) lead to SMARD1, but clinical criteria that delineate SMARD1 from other SMARD syndromes are not well established. Here we present a retrospective clinical and genetic study to determine the criteria that would predict the presence or absence of IGHMBP2 mutations. From 141 patients with respiratory distress and a spinal muscular atrophy phenotype we recorded the clinical features through a questionnaire and sequenced the entire coding region of IGHMBP2. In 47 (33%) patients we identified IGHMBP2 mutations, 14 of which were not described before. Clinical features and combinations thereof associated with the presence of IGHMBP2 mutations were discovered through hierarchical cluster analysis. This method detects common traits not evident at first sight by grouping items according to their similarity. The combination of "manifestation of respiratory failure between 6 weeks and 6 months" AND ("presence of diaphragmatic eventration" OR "preterm birth") predicted the presence of IGHMBP2 mutations with 98% sensitivity and 92% specificity. Non-SMARD1 patients fell into two different symptom clusters, mainly separated by the age at respiratory failure and the presence of multiple congenital contractures. The 14 novel IGHMBP2 mutations comprised missense, frameshift, splice-site, and nonsense mutations. All missense mutations altered conserved residues within or adjacent to the putative DNA helicase domain. The c.1235+3A>G splice-site mutation did not entirely suppress correct splicing and we found a residual wild-type IGHMBP2 mRNA steady-state level of 24.4+/-6.9%, which was, however, not sufficient to avert SMARD1 in this patient.

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Section: Patient Cohort Studymentioning

confidence: 63%

Clinical and mutational profile in spinal muscular atrophy with respiratory distress (SMARD): defining novel phenotypes through hierarchical cluster analysis

et al. 2007

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“…Distal HMN type III (distal SMA 3) is linked to a mutation which is located on chromosome 11q13 telomeric to the IGHMBP2 gene, but the gene has not been defined (Viollet et al, 2004). Early, infantile onset was reported in the most severely affected member of a Lebanese family with distal HMN type III, who acquired walking ability at the age of 6 years (Pearn & Hudgson 1979).…”

Section: Distal Hereditary Motor Neuropathies (Distal Hmn)mentioning

confidence: 99%

Charcot‐Marie‐Tooth Disease: A Clinico‐genetic Confrontation

Barišić

Claeys

Sirotković-Skerlev

et al. 2008

Annals of Human Genetics

146

154

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SummaryCharcot-Marie-Tooth disease (CMT) is the most common neuromuscular disorder. It represents a group of clinically and genetically heterogeneous inherited neuropathies. Here, we review the results of molecular genetic investigations and the clinical and neurophysiological features of the different CMT subtypes. The products of genes associated with CMT phenotypes are important for the neuronal structure maintenance, axonal transport, nerve signal transduction and functions related to the cellular integrity. Identifying the molecular basis of CMT and studying the relevant genes and their functions is important to understand the pathophysiological mechanisms of these neurodegenerative disorders, and the processes involved in the normal development and function of the peripheral nervous system. The results of molecular genetic investigations have impact on the appropriate diagnosis, genetic counselling and possible new therapeutic options for CMT patients.

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“…Type 3, an autosomal recessive distal spinal muscular atrophy without respiratory distress, has recently been linked to 11q13. 34 This condition starts when patients are between 2 and 10 years of age and progresses slowly. The more severe autosomal recessive form may be present at birth, manifesting with weakness and severe respiratory distress secondary to diaphragmatic paralysis.…”

Section: Distribution Of Muscle Weaknessmentioning

confidence: 99%

Spinal Muscular Atrophy: Clinical Classification and Disease Heterogeneity

2007

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The clinical classification of spinal muscular atrophy, caused by deletion of the survival motor neuron 1 gene (SMN1), is based on age at onset and maximum function achieved. Evidence suggests that maximum function achieved is more closely related to life expectancy than age at onset. Therefore, it is important to wait for a period before assigning a patient to 1 of 5 classes of the disorder. Several diseases result from degeneration of the anterior horn cell but are not caused by SMN1. The classification for these conditions is evolving. This article offers an attempt at organizing one's thinking about this disease group.

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Refined genetic mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.3 and evidence of linkage disequilibrium in European families

Cited by 14 publications

References 9 publications

Clinical and mutational profile in spinal muscular atrophy with respiratory distress (SMARD): defining novel phenotypes through hierarchical cluster analysis

Clinical and mutational profile in spinal muscular atrophy with respiratory distress (SMARD): defining novel phenotypes through hierarchical cluster analysis

Charcot‐Marie‐Tooth Disease: A Clinico‐genetic Confrontation

Spinal Muscular Atrophy: Clinical Classification and Disease Heterogeneity

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