HMSNL in a 13-year-old Bulgarian girl

Baethmann, Martina; Göhlich-Ratmann, G.; Schröder, Johann Michael; Kalaydjieva, Luba; Voït, Thomas

doi:10.1016/s0960-8966(98)00011-x

Cited by 37 publications

(28 citation statements)

References 9 publications

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“…The participating centres have reported consistent clinical ®ndings which allow the de®nition of the HMSNL phenotype [1,3,4,6,7]. Onset of symptoms is in the ®rst decade of life.…”

Section: The Hmsnl Phenotypementioning

confidence: 88%

Hereditary motor and sensory neuropathy – Lom (HMSNL): refined genetic mapping in Romani (Gypsy) families from several European countries

Chandler

Angelicheva

Heather

et al. 2000

Neuromuscular Disorders

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Hereditary motor and sensory neuropathy type Lom, initially identi®ed in Roma (Gypsy) families from Bulgaria, has been mapped to 8q24. Further re®ned mapping of the region has been undertaken on DNA from patients diagnosed across Europe. The re®ned map consists of 25 microsatellite markers over approximately 3 cM. In this collaborative study we have identi®ed a number of historical recombinations resulting from the spread of the hereditary motor and sensory neuropathy type Lom gene through Europe with the migration and isolation of Gypsy groups. Recombination mapping and the minimal region of homozygosity reduced the original 3 cM hereditary motor and sensory neuropathy type Lom region to a critical interval of about 200 kb. q

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“…The participating centres have reported consistent clinical ®ndings which allow the de®nition of the HMSNL phenotype [1,3,4,6,7]. Onset of symptoms is in the ®rst decade of life.…”

Section: The Hmsnl Phenotypementioning

confidence: 88%

Hereditary motor and sensory neuropathy – Lom (HMSNL): refined genetic mapping in Romani (Gypsy) families from several European countries

Chandler

Angelicheva

Heather

et al. 2000

Neuromuscular Disorders

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“…The disorder was first described in affected families from Bulgaria (Kalaydjieva et al 1996) and was subsequently diagnosed in families in Italy (Merlini et al 1998), Slovenia (Butinar et al 1999), Germany (Baethmann et al 1998), Spain (Colomer et al 2000), France, and Rumania. HMSNL is an earlyonset peripheral neuropathy that progresses to severe disability in adulthood.…”

Section: Introductionmentioning

confidence: 99%

“…HMSNL is an earlyonset peripheral neuropathy that progresses to severe disability in adulthood. Clinically, it presents with muscle weakness and wasting, tendon areflexia, skeletal and foot deformities, sensory loss affecting all modalities, and severe reduction in nerve conduction velocities (Baethmann et al 1998;Kalaydjieva et al 1998;Merlini et al 1998;Butinar et al 1999). Neural deafness develops during the second or third decade of life, with abnormalities in the brain-stem auditoryevoked potentials suggesting involvement of the entire tract, including the central auditory pathways Butinar et al 1999).…”

Section: Introductionmentioning

confidence: 99%

“…Neural deafness develops during the second or third decade of life, with abnormalities in the brain-stem auditoryevoked potentials suggesting involvement of the entire tract, including the central auditory pathways Butinar et al 1999). The neuropathologic observations in HMSNL (Baethmann et al 1998;Kalaydjieva et al 1998;Butinar et al 1999;King et al 1999) include Schwann-cell dysfunction, which is manifested by hypomyelination and demyelination/remyelination, failure of compaction of the innermost myelin lamellae, and poor hypertrophic response (onion-bulb formation) to the demyelination process. At the same time, axonal involvement is documented by early, severe, and progressive axonal loss and by the presence of curvilinear intra-axonal inclusions that are similar to those seen in the dying-back type of distal axonopathy in experimental vitamin E deficiency.…”

Section: Introductionmentioning

confidence: 99%

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N‐MYC Downstream‐Regulated Gene 1 Is Mutated In Hereditary Motor And Sensory Neuropathy‐LOM

Kalaydjieva¹,

Gresham²,

Gooding³

et al. 2001

J Peripheral Nervous Sys

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Citation for published version (APA):Kalaydjieva, L., Gresham, D., Gooding, R., Heather, L., Baas, F., de Jonge, R., ... Thomas, P. K. (2000). N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom. American Journal of Human Genetics, 67, 47-58. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Download date: 11 May 2018Am. J. Hum. Genet. 67:47-58, 2000 47 Hereditary motor and sensory neuropathies, to which Charcot-Marie-Tooth (CMT) disease belongs, are a common cause of disability in adulthood. Growing awareness that axonal loss, rather than demyelination per se, is responsible for the neurological deficit in demyelinating CMT disease has focused research on the mechanisms of early development, cell differentiation, and cell-cell interactions in the peripheral nervous system. Autosomal recessive peripheral neuropathies are relatively rare but are clinically more severe than autosomal dominant forms of CMT, and understanding their molecular basis may provide a new perspective on these mechanisms. Here we report the identification of the gene responsible for hereditary motor and sensory neuropathy-Lom (HMSNL). HMSNL shows features of Schwann-cell dysfunction and a concomitant early axonal involvement, suggesting that impaired axonglia interactions play a major role in its pathogenesis. The gene was previously mapped to 8q24.3, where conserved disease haplotypes suggested genetic homogeneity and a single founder mutation. We have reduced the HMSNL interval to 200 kb and have characterized it by means of large-scale genomic sequencing. Sequence analysis of two genes located in the critical region identified the founder HMSNL mutation: a premature-termination codon at position 148 of the N-myc downstream-regulated gene 1 (NDRG1). NDRG1 is ubiquitously expressed and has been proposed to play a role in growth arrest and cell differentiation, possibly as a signaling protein shuttling between the cytoplasm and the nucleus. We have studied expression in peripheral nerve and have detected particularly high levels in the Schwann cell. Taken together, these findings point to NDRG1 having a role in the peripheral nervous system, possibly in the Schwann-cell signaling necessary for axonal survival. N-myc Downstream-Regulated Gene 1 Is Muta...

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“…1 Several of these patients have an associated hereditary motor and sensory neuropathy (HMSN). 2 Recently, Gypsy families originating from Lom, Bulgaria, 9,10 northern Italy, 11 and a non-Gypsy Bulgarian patient 12 were described with HMSN and deafness. Sural nerve biopsy revealed both a demyelinating disorder and a significant loss of large axons.…”

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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

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HMSNL in a 13-year-old Bulgarian girl

Cited by 37 publications

References 9 publications

Hereditary motor and sensory neuropathy – Lom (HMSNL): refined genetic mapping in Romani (Gypsy) families from several European countries

Hereditary motor and sensory neuropathy – Lom (HMSNL): refined genetic mapping in Romani (Gypsy) families from several European countries

N‐MYC Downstream‐Regulated Gene 1 Is Mutated In Hereditary Motor And Sensory Neuropathy‐LOM

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

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