Founder Effect and Estimation of the Age of the c.892C&gt;T (p.Arg298Cys) Mutation in <i>LMNA</i> Associated to Charcot‐Marie‐Tooth Subtype CMT2B1 in Families from North Western Africa

Hamadouche, Tarik; Poitelon, Yannick; Génin, Emmanuelle; Chaouch, Malika; Tazir, M.; Kassouri, Nora; Nouioua, Sonia; Chaouch, Amina; Boccaccio, Irène; Benhassine, Traki; Sandre-Giovannoli, Annachiara De; Grid, Djamel; Lévy, Nicolas; Delague, Valérie

doi:10.1111/j.1469-1809.2008.00456.x

Cited by 26 publications

(15 citation statements)

References 24 publications

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“…Corresponding percentages are given in parentheses. demonstrated to share a common ancestral haplotype of about 1.0 Mb and that the most recent common ancestor would have lived approximately 800-900 years ago[42].…”

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confidence: 99%

Clinical and genetic heterogeneity in laminopathies

Bertrand

Chikhaoui

Yaou

et al. 2011

Biochemical Society Transactions

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Mutations in the LMNA gene encoding lamins A/C are responsible for more than ten different disorders called laminopathies which affect various tissues in an isolated (striated muscle, adipose tissue or peripheral nerve) or systemic (premature aging syndromes) fashion. Overlapping phenotypes are also observed. Associated with this wide clinical variability, there is also a large genetic heterogeneity, with 408 different mutations being reported to date. Whereas a few hotspot mutations emerge for some types of laminopathies, relationships between genotypes and phenotypes remain poor for laminopathies affecting the striated muscles. In addition, there is important intrafamilial variability, explained only in a few cases by digenism, thus suggesting an additional contribution from modifier genes. In this regard, a chromosomal region linked to the variability in the age at onset of myopathic symptoms in striated muscle laminopathies has recently been identified. This locus is currently under investigation to identify modifier variants responsible for this variability.

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confidence: 99%

Clinical and genetic heterogeneity in laminopathies

Bertrand

Chikhaoui

Yaou

et al. 2011

Biochemical Society Transactions

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“…8 All CMT2B1 patients, homozygous for this mutation, originate from a restricted region of north-west Algeria and eastern Morocco and carry a homozygous common ancestral haplotype at the LMNA locus. 21 Two other mutations in the LMNA gene have been identified in patients with peripheral neuropathy, but always in combination with other clinical signs. 15,16 Recently, authors from China published results similar to ours with the absence of LMNA mutations in 32 sporadic CMT2 patients.…”

Section: Discussionmentioning

confidence: 99%

Mutations in the LMNA gene do not cause axonal CMT in Czech patients

et al. 2009

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The LMNA gene was sequenced in 98 Czech patients from 94 unrelated families with early-onset axonal Charcot-Marie-Tooth (CMT) disease consistent with both autosomal recessive inheritance and sporadic cases. Biallelic pathogenic mutations were not found in any patient in this group. One patient carried the c.1870C4T mutation that is predicted to result in the amino-acid substitution, p. Arg624Cys, on one allele, but the second causative mutation was not detected. LMNA mutation is not likely to be associated with the disease in this family. To exclude larger deletions/duplications in the LMNA gene not detectable by sequencing, 48 patients from this group were also analyzed with multiplex ligation-dependent probe amplification. No rearrangements in the LMNA gene were detected. We conclude that mutations in the LMNA gene are absent from a large group of Czech patients with axonal autosomal recessive CMT disease. Consequently, LMNA mutation screening does not seem to be relevant for axonal CMT DNA diagnostics. A similar situation may apply to other European populations.

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“…If there is access to brainstem auditory responses, these are often abnormal in patients with CMTX. CMT2B1, an axonal subtype of CMT with onset in the second decade of life, is prevalent in northwestern Africa (northwest Algeria and east of Morocco); a founder effect is suggested [75]. In the neuromuscular clinic at the Red Cross War Memorial Children's Hospital in South Africa, children with hereditary neuropathies in the indigenous African population are dominated by axonal forms of CMT.…”

Section: Molecular Genetic Analysesmentioning

confidence: 99%

Diagnosis and Management of Pediatric Peripheral Neuropathies In Resource-Poor Settings

Wilmshurst

2013

Future Neurol.

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The diagnosis of a peripheral neuropathy in a child who resides in the majority of resource-poor settings is based on the history taken and the clinical examination. The majority of children, unless they demonstrate additional clinical markers, will lack a more definitive diagnosis beyond the label ‘peripheral neuropathy’. The treatable, typically acquired conditions, which are prevalent in these settings, are the priority to identify. This would include neuroinfections, neuroinflammation, toxins and vitamin deficiencies. The management of children with peripheral neuropathies in resource-poor settings must be approached in a different manner to that of more ‘resource-equipped’ settings. Secondary or tertiary centers are scarce, often significant distances away from the patient, and this leads to long delays before access is possible. Most children present to primary healthcare settings and are seen by practitioners with little training in the features suggestive of a peripheral neuropathy. As such, basic aids to assist the healthcare worker in the early recognition and interventions of a child with a peripheral neuropathy are important. In addition, there must be recognition of the child with a rapidly progressive neuropathy where a life-threatening condition is present, and urgent referral to a tertiary setting made wherever possible.

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Founder Effect and Estimation of the Age of the c.892C>T (p.Arg298Cys) Mutation in LMNA Associated to Charcot‐Marie‐Tooth Subtype CMT2B1 in Families from North Western Africa

Cited by 26 publications

References 24 publications

Clinical and genetic heterogeneity in laminopathies

Clinical and genetic heterogeneity in laminopathies

Mutations in the LMNA gene do not cause axonal CMT in Czech patients

Diagnosis and Management of Pediatric Peripheral Neuropathies In Resource-Poor Settings

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