Screening of the 17p11.2–p12 region in a large cohort of patients with Charcot-Marie-Tooth (CMT) disease or hereditary neuropathy with liability to pressure palsies (HNPP)

Abstract

Within the last decade, numerous methods have been applied to detect the most common mutation in patients affected with Charcot-Marie-Tooth (CMT) disease, i.e. submicroscopic duplication in the 17p11.2--p12 region. In 1993, another neuropathy - known as hereditary neuropathy with liability to pressure palsies (HNPP) - has been shown to be caused by a 17p11.2--p12 deletion. Historically, Southern blot analysis was the first approach to identify CMT1A duplication or HNPP deletion. This time- and labor-consuming method requires prior selection of DNA samples. In fact, only CMT patients affected with the demyelinating form of CMT1 have been screened for CMT1A duplication. After the 17p11.2--p12 duplication was identified in the CMT1 families, subsequent studies revealed additional axonal features in the patients harboring the 17p11.2--p12 duplication. Thus it seems reasonable to test all patients affected with CMT for the presence of the 17p11.2--p12 duplication. To evaluate the utility of real-time polymerase chain reaction (Q-PCR) and restriction fragment length polymorphism PCR (RFLP-PCR), we screened a large group of 179 families with the diagnosis of CMT/HNPP for the presence of the 17p11.2--p12 duplication/deletion. Due to a high frequency of CMT1A duplication in familial cases of CMT, we propose (in contrast to the previous studies) to perform Q-PCR analysis in all patients diagnosed with CMT.

Mutation analysis of PMP22 in Slovak patients with Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies

“…Nevertheless, PMP22 copy number determination identified a total of 7 families with deletion, thus the ratio of deletion to duplication is 1 to 5.7. This difference in the number of detected deletions and duplications is similar to the outcome of a European collaborative study by Nelis et al (1996), although there are publications that reported markedly higher and markedly lower ratios (Silander et al 1998;Kabzinska et al 2009). …”

Elderly‐onset case of hereditary neuropathy with liability to pressure palsies: A case report

“…5 It is known that PMP22 gene dosage is related to clinical course of Charcot-Marie-Tooth disease type 1A and HNPP, 6 and HNPP patients have less dosage of PMP22 gene compared to healthy controls. 7 Our patient with elderly onset of HNPP might have had PMP22 gene dosage close to healthy controls; however, the dosage of the patient was not evaluated. Further studies are needed to elucidate the genotype related to elderly onset of HNPP.…”

The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases

“…The Q-PCR reaction was performed on the ABI-7500 Real-Time PCR system (Applied Biosystems). The relative dosage (RQ) of the PMP22 gene ranges from 0.700 to 1.090 in normal individuals (two copies of the PMP22 gene), from 0.359 to 0.595 in HNPP patients (one copy of the PMP22 gene), and from 1.176 to 2.324 in CMT1A patients (three copy of the PMP22 gene) [ 5 ].…”