Hereditary neuropathy with liability to pressure palsy (HNPP): report of a family with a new point mutation in PMP22 gene

Fusco, Carlo; Spagnoli, Carlotta; Salerno, Grazia Gabriella; Pavlidis, Elena; Frattini, Daniele; Pisani, Francesco

doi:10.1186/s13052-017-0414-4

Cited by 15 publications

(19 citation statements)

References 31 publications

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“… 10 A deletion of the same gene (PMP22) results in hereditary neuropathy with liability to pressure palsy exhibiting a different type of neuropathy. 11 The function of the PMP22 gene is likely to modulate myelin production, differentiation, and death. CMT1 and its subtypes usually present with weakness in distal muscles of the leg with loss of deep tendon reflexes, distal calf atrophy, pes cavus, and hammertoe, and they are associated with late findings of atrophy of intrinsic muscles of the hand and palpable enlargement of peripheral nerves.…”

Section: Discussionmentioning

confidence: 99%

Unmasking a Case of Asymptomatic Charcot-Marie-Tooth Disease (CMT1A) With Vincristine

Jariwal

Shoua

Sabetian

et al. 2018

Journal of Investigative Medicine High Impact Case Reports

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Charcot-Marie-Tooth (CMT) disease is a hereditary demyelinating disease of the peripheral nervous system that results in sensory and motor dysfunction. CMT includes a spectrum of diseases with different types of mutations in the genes encoding myelin protein, resulting in a variety of dysfunctions in its life cycle. In CMT subtype 1A there is duplication mutation of peripheral myelin protein 22 gene on chromosome 17. Incomplete penetrance, gene-dosage effect, and variable expressivity can attribute to the asymptomatic nature of the disease in some subset of patients. Vincristine administration is contraindicated in patients who are alrea\dy diagnosed with CMT disease. We report a case of asymptomatic CMT disease unmasked only by the neurotoxic effects of vincristine. Genetic testing for a patient with a preexisting family background of inherited diseases before starting vincristine therapy can potentially prevent a disability.

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Section: Discussionmentioning

confidence: 99%

Unmasking a Case of Asymptomatic Charcot-Marie-Tooth Disease (CMT1A) With Vincristine

Jariwal

Shoua

Sabetian

et al. 2018

Journal of Investigative Medicine High Impact Case Reports

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“… 1 Most cases are caused by the deletion of PMP22 at chromosome 17p11.2–p12, and rarely also by a point mutation within the gene. 2 3 4 Here we report ultrasonography and genetic findings in an HNPP patient with a novel point mutation in PMP22 .…”

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confidence: 86%

Ultrasonography Findings in Hereditary Neuropathy with Liability to Pressure Palsies due to Single-Nucleotide Substitution

Kim

Jeong

et al. 2020

J Clin Neurol

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Dear Editor, Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant demyelinating neuropathy characterized by recurrent entrapment neuropathies such as ulnar and peroneal nerve palsy. Its prevalence has been estimated at 7-16 per 100,000 people. 1 Most cases are caused by the deletion of PMP22 at chromosome 17p11.2-p12, and rarely also by a point mutation within the gene. 2-4 Here we report ultrasonography and genetic findings in an HNPP patient with a novel point mutation in PMP22. A 27-year-old man visited our clinic due to right-arm weakness that recurred 2 weeks earlier while carrying a heavy object. The patient had suffered the same symptom 5-years previously, but otherwise had no known underlying disease. A neurologic examination revealed MRC grade IV weakening of the extensor of the right wrist and metacarpophalangeal joint. A nerve conduction study (NCS) showed a conduction block in the right radial nerve. Generalized prolongations of terminal latency and F-wave latency were observed. The NCS findings for the patient's median and ulnar nerves were similar to those seen in carpal tunnel and cubital tunnel syndrome. Ultrasonography examinations of the cervical root and nerves of the upper and lower extremities revealed enlargement only in the median and ulnar nerves at the wrist and at the elbow, respectively (Fig. 1). The NCS and ultrasonography results obtained 5-years previously were the same except for the absence of radial nerve conduction block. The patient was clinically diagnosed with HNPP. However, the deletion of PMP22 had not been detected in the multiplex ligation-dependent probe amplification assay performed 5 years previously, and so we performed next-generation sequencing to identify any pathogenic variant. A null variant (NM_000304.3: c.79-2A>C) in the PMP22 was detected, which was confirmed by Sanger's sequencing. We regarded this as a pathogenic variant causing HNPP and so diagnosed him with HNPP. The patient fully recovered after 3 months of rest. Most (84%) HNPP patients exhibit PMP22 deletion, 5 but a point mutation within the gene can also cause this condition. 2-4 The c.79-2A>C variant identified in the present study is a novel variant. However, we were able to classify this variant as pathogenic based on the following evidence: 1) it is a null variant in a gene with loss-of-function mechanism, 2) it is not included in the controls in the Genome Aggregation Database (http://gnomad.broadinstitute.org), 3) multiple lines of computational evidence support a deleterious effect of the gene, and 4) the patient's phenotype was highly specific for a disease with a single genetic etiology. 6 Additionally, the c.79-2A>G variant-which is a different nucleotide change at the same position-was previously reported as a pathogenic variant associated with HNPP. 2 The swelling of peripheral nerves at common entrapment sites has been reported in HNPP-the median nerve at the wrist and ulnar nerve at the elbow-even without symp

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“…Deletion of PMP22 causes hereditary neuropathy with liability to pressure palsies (HNPP). Patients manifest episodic focal neuropathies at entrapment sites or susceptible pressure points . Point mutations in PMP22 cause the rare subtype of CMT1.…”

Section: Introductionmentioning

confidence: 99%

Homozygous splice‐site mutation c.78 + 5G>A in PMP22 causes congenital hypomyelinating neuropathy

Jun

Meng

et al. 2019

Neuropathology

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Congenital hypomyelinating neuropathy (CHN) presents in the neonatal period and results in delayed development of sensory and motor functions due to several gene mutations including in EGR2, MPZ, CNTNAP1, and PMP22. The phenotype of homozygous splice-site mutation in the PMP22 gene has not been described in humans or animal models. Here we describe a family carrying a pathogenic splice-site c.78 + 5G>A mutation in the PMP22 gene. We evaluated the clinical, electrophysiological, histological, and genetic features of the family. The proband with homozygous mutation presented with CHN, while his consanguineous parents with heterozygous mutation were asymptomatic. The proband was a 7-year-old boy. He had motor retardation after birth and had remained unable to walk independently at the time of the study. The compound muscle action potentials and sensory nerve action potentials were not recordable in the boy. The motor and sensory nerve conduction velocities of the parents were slightly to moderately decreased, although they had no symptoms of peripheral neuropathy. The sural nerve biopsy of the boy revealed hypomyelinating neuropathy with absence of large myelinated fibers, no myelin breakdown products, and numerous basal lamina onion bulb formations. To our knowledge, this is the first report of a homozygous splice-site mutation in the PMP22 gene in humans. Our study expands the phenotype and genotype of PMP22-related neuropathy.

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Hereditary neuropathy with liability to pressure palsy (HNPP): report of a family with a new point mutation in PMP22 gene

Cited by 15 publications

References 31 publications

Unmasking a Case of Asymptomatic Charcot-Marie-Tooth Disease (CMT1A) With Vincristine

Unmasking a Case of Asymptomatic Charcot-Marie-Tooth Disease (CMT1A) With Vincristine

Ultrasonography Findings in Hereditary Neuropathy with Liability to Pressure Palsies due to Single-Nucleotide Substitution

Homozygous splice‐site mutation c.78 + 5G>A in PMP22 causes congenital hypomyelinating neuropathy

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