Mutational analysis of PMP22, GJB1 and MPZ in Greek Charcot-Marie-Tooth type 1 neuropathy patients

Karadima, Georgia; Floroskufi, Paraskewi; Vassilopoulos, D.; Πάνας, Μάριος

doi:10.1111/j.1399-0004.2011.01657.x

Cited by 14 publications

(25 citation statements)

References 27 publications

(15 reference statements)

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“…Of these, CMT1X was most common (24%), followed by CMT1A (20%), HNPP (12%), and CMT1B (4%). This pattern differs from that seen in other populations, including those from China, Korea, Japan, and Turkey, where CMT1A predominates (Table ) . Although this difference could be due to the small numbers of patients, the high proportion of CMT1X in our population is both novel and of interest.…”

Section: Discussioncontrasting

confidence: 79%

X‐linked Charcot–Marie–Tooth disease predominates in a cohort of multiethnic Malaysian patients

et al. 2013

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Section: Discussioncontrasting

confidence: 79%

X‐linked Charcot–Marie–Tooth disease predominates in a cohort of multiethnic Malaysian patients

et al. 2013

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“…The duplication frequency using MLPA was 52.3%, higher than our previous estimation (p = 0.0001) and similar to frequencies reported in most populations (1). In familial cases the frequency was 66.6% (52/78) and in non-familial cases 30% (15/50).…”

supporting

confidence: 85%

“…Inclusion criteria were similar to our previous study (1). Seventy-eight cases were familial (60.9%) and 50 non-familial (39.1%).…”

mentioning

confidence: 94%

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Reevaluation of the CMT1A duplication frequency in Greek Charcot‐Marie‐Tooth type 1 patients

2014

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In our previous study published in Clinical Genetics we estimated the frequency of the 1.4-Mb CMT1Aduplication in the Greek population at 25.9%, a figure significantly lower than reports from most other populations. We noted at the time that the reduced sensitivity of the long polymerase chain reaction (PCR) method used for detecting the duplication may have been partly responsible for underestimating the duplication frequency (1).To re-evaluate the duplication frequency with a method that is almost 100% sensitive, we screened 128 consecutive Greek CMT1 index cases presenting from 2006 to 2013 using Multiplex Ligation-dependent Probe Amplification (MLPA) (2, 3). Inclusion criteria were similar to our previous study (1). Seventy-eight cases were familial (60.9%) and 50 non-familial (39.1%). Informed consent was obtained from all participants.The duplication frequency using MLPA was 52.3%, higher than our previous estimation (p = 0.0001) and similar to frequencies reported in most populations (1). In familial cases the frequency was 66.6% (52/78) and in non-familial cases 30% (15/50). Subsequent screening of the 128 cases with long PCR revealed an overall sensitivity of 67.16%, lower than figures quoted in the literature (84-87%) (2, 4). In familial cases the sensitivity was lower (59.6%) compared to non-familial cases (93.3%, p = 0.014). This indicates that in familial Greek CMT1A cases the recombination event has ∼40% possibility of occurring outside the usual 3.2-kb recombination hotspot, rather than the usually quoted figure of <25%, possibly because of relative genetic isolation (5). In the Greek population, therefore, the sensitivity of long PCR depends on the characteristics of the patient sample. The more familial cases the lower the sensitivity. Given a 75.3% of familial cases in our original sample, this largely explains our earlier underestimation of the duplication frequency (1). In conclusion, a more accurate estimation of the CMT1A-duplication frequency in Greek patients is ∼50%, similar to other ethnic populations.

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“…Several more recent epidemiological studies [22-25] reported prevalences of CMT ranging from 1:1,214 (in Norway) to 1:6,500 (in the United Kingdom). Epidemiological studies show that 19.6% to 64.7% of CMT patients carry the PMP22 duplication [22,25], which gives calculated prevalences of CMT1A in the range of 1:3,800 to 1:12,500.…”

Section: Pmp22 Duplication – Charcot-marie-tooth Disease Type 1a (Cmt1a)mentioning

confidence: 99%

PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

Paassen

Kooi

Spaendonck‐Zwarts

et al. 2014

Orphanet J Rare Dis

145

121

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PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is usually reported as 1:2,500, epidemiological studies show that 20-64% of CMT patients carry the PMP22 duplication. The prevalence of HNPP is not well known. CMT1A usually presents in the first two decades with difficulty walking or running. Distal symmetrical muscle weakness and wasting and sensory loss is present, legs more frequently and more severely affected than arms. HNPP typically leads to episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve. Electrophysiological evaluation is needed to determine whether the polyneuropathy is demyelinating. Sonography of the nerves can be useful. Diagnosis is confirmed by finding respectively a PMP22 duplication, deletion or point mutation. Differential diagnosis includes other inherited neuropathies, and acquired polyneuropathies. The mode of inheritance is autosomal dominant and de novo mutations occur. Offspring of patients have a chance of 50% to inherit the mutation from their affected parent. Prenatal testing is possible; requests for prenatal testing are not common. Treatment is currently symptomatic and may include management by a rehabilitation physician, physiotherapist, occupational therapist and orthopaedic surgeon. Adult CMT1A patients show slow clinical progression of disease, which seems to reflect a process of normal ageing. Life expectancy is normal.

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Mutational analysis of PMP22, GJB1 and MPZ in Greek Charcot-Marie-Tooth type 1 neuropathy patients

Cited by 14 publications

References 27 publications

X‐linked Charcot–Marie–Tooth disease predominates in a cohort of multiethnic Malaysian patients

X‐linked Charcot–Marie–Tooth disease predominates in a cohort of multiethnic Malaysian patients

Reevaluation of the CMT1A duplication frequency in Greek Charcot‐Marie‐Tooth type 1 patients

PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

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