Dejerine-Sottas disease with sensorineural hearing loss, nystagmus, and peripheral facial nerve weakness: de novo dominant point mutation of the PMP22 gene.

Ionâşescu, Victor; Searby, C; Greenberg, SA

doi:10.1136/jmg.33.12.1048

Cited by 40 publications

(26 citation statements)

References 5 publications

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“…Most mutations were found in CMT1 patients, but two (Ser76Ile and Ser72Leu) mutations occurred in patients having clinical phenotypes of DSD [9,11]. All mutations are positioned at the extracellular borders of the first, second or third transmembrane domains, suggesting that defective interactions with other proteins in Schwann cells may result in a myelination failure of the peripheral nerve including the auditory nerve [10].…”

Section: Discussionmentioning

confidence: 99%

A novel point mutation in PMP22 gene associated with a familial case of Charcot-Marie-Tooth disease type 1A with sensorineural deafness

Joo

et al. 2004

Neuromuscular Disorders

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Section: Discussionmentioning

confidence: 99%

A novel point mutation in PMP22 gene associated with a familial case of Charcot-Marie-Tooth disease type 1A with sensorineural deafness

Joo

et al. 2004

Neuromuscular Disorders

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“…More recently, gas3/PMP22 point mutations responsible for both CMT1A and DSS also have been associated with deafness (Ionasescu et al, 1996;Kovach et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Exposure at the Cell Surface Is Required for Gas3/PMP22 To Regulate Both Cell Death and Cell Spreading: Implication for the Charcot–Marie–Tooth Type 1A and Dejerine–Sottas Diseases

Brancolini

Edomi

Marzinotto

et al. 2000

MBoC

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Gas3/PMP22 is a tetraspan membrane protein highly expressed in myelinating Schwann cells. Point mutations in thegas3/PMP22 gene account for the dominant inherited peripheral neuropathies Charcot–Marie–Tooth type 1A disease (CMT1A) and Dejerine–Sottas syndrome (DSS). Gas3/PMP22 can regulate apoptosis and cell spreading in cultured cells.Gas3/PMP22 point mutations, which are responsible for these diseases, are defective in this respect. In this report, we demonstrate that Gas3/PMP22-WT is exposed at the cell surface, while its point-mutated derivatives are intracellularly retained, colocalizing mainly with the endoplasmic reticulum (ER). The putative retrieval motif present in the carboxyl terminus of Gas3/PMP22 is not sufficient for the intracellular sequestration of its point-mutated forms. On the contrary, the introduction of a retrieval signal at the carboxyl terminus of Gas3/PMP22-WT leads to its intracellular accumulation, which is accompanied by a failure to trigger cell death as well as by changes in cell spreading. In addition, by substituting the Asn at position 41 required for N-glycosylation, we provide evidence that N-glycosylation is required for the full effect on cell spreading, but it is not necessary for triggering cell death. In conclusion, we suggest that the DSS and the CMT1A neuropathies derived from point mutations ofGas3/PMP22 might arise, at the molecular level, from a reduced exposure of Gas3/PMP22 at the cell surface, which is required to exert its biological functions.

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“…Vestibular neuropathies have also been described in patients with HMSN in the past. 16 The absence of symptoms of vestibular disorder in our patients may be the result of the gradual occurrence of a bilateral vestibular disorder, allowing the development of mechanisms that compensate for altered vestibular inputs.…”

Section: Arrows) Onion Bulb Formations Are Not Evident (Paraphenylinmentioning

confidence: 99%

“…These disorders involve optic nerves, 30 phrenic and vagal nerves, 31 facial and vestibular nerves, 16 trigeminal nerve, 32 and auditory nerve. [33][34][35] Other sensory nerve involvement (olfaction and taste) has not been specifically commented on.…”

Section: Arrows) Onion Bulb Formations Are Not Evident (Paraphenylinmentioning

confidence: 99%

Hereditary auditory, vestibular, motor, and sensory neuropathy in a Slovenian Roma (Gypsy) kindred

et al. 1999

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Members of a Roma (Gypsy) family with hereditary motor and sensory peripheral neuropathy (HMSN) and concomitant auditory and vestibular cranial neuropathies were identified in Kocevje, Slovenia. The illness begins in childhood with a severe and progressive motor disability and the deafness is delayed until the second decade. There are no symptoms of vestibular dysfunction. The family structure is consistent with an autosomal recessive pattern of inheritance and the genetic locus for the disorder is linked to the same region of chromosome 8q24 as other Roma families with HMSN and deafness from Lom, Bulgaria (HMSN‐Lom). The present study shows that the deafness is caused by a neuropathy of the auditory nerve with preserved measures of cochlear outer hair cell function (otoacoustic emissions and cochlear microphonics) but absent neural components of auditory brainstem potentials. The hearing loss affects speech comprehension out of proportion to the pure tone loss. Vestibular testing showed absence of caloric responses. Physiological and neuropathological studies of peripheral nerves were compatible with the nerve disorder contemporaneously affecting Schwann cells and axons resulting in both slowed nerve conduction and axonal loss. Genetic linkage studies suggest a refinement of the 8q24 critical region containing the HMSN‐Lom locus that affects peripheral motor and sensory nerves as well as the cranial auditory and vestibular nerves. Ann Neurol 1999;46:36–44

show abstract

Dejerine-Sottas disease with sensorineural hearing loss, nystagmus, and peripheral facial nerve weakness: de novo dominant point mutation of the PMP22 gene.

Cited by 40 publications

References 5 publications

A novel point mutation in PMP22 gene associated with a familial case of Charcot-Marie-Tooth disease type 1A with sensorineural deafness

A novel point mutation in PMP22 gene associated with a familial case of Charcot-Marie-Tooth disease type 1A with sensorineural deafness

Exposure at the Cell Surface Is Required for Gas3/PMP22 To Regulate Both Cell Death and Cell Spreading: Implication for the Charcot–Marie–Tooth Type 1A and Dejerine–Sottas Diseases

Hereditary auditory, vestibular, motor, and sensory neuropathy in a Slovenian Roma (Gypsy) kindred

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