Abstract
Mutations in the gene for the ganglioside-induced differentiation-associated protein-1 (GDAP1) on 8q21 recently were reported to cause autosomal recessive Charcot-Marie-Tooth (CMT) sensorimotor neuropathy. Neurophysiology and nerve pathology were heterogeneous in these cases: a subset of GDAP1 mutations was associated with peripheral nerve demyelination, whereas others resulted in axonal degeneration. In this study, we identified two novel mutations disrupting the GDAP1 reading frame. Homozygosity for a single base pair insertion in exon 3 (c.349_350insT) was observed in affected children from a Turkish inbred pedigree. The other novel allele detected in a German patient was a homozygous mutation of the intron 4 donor splice site (c.579 + 1G>A). Patients with GDAP1 mutations displayed severe, early childhood-onset CMT neuropathy with prominent pes equinovarus deformity and impairment of hand muscles. Nerve conduction velocities were between 25 and 35 m/s and peripheral nerve pathology showed axonal as well as demyelinating changes. These findings fitted the definition of intermediate type CMT and further support the view that GDAP1 is vital for both, axonal integrity and Schwann cell properties.
| Original language | English |
|---|---|
| Pages (from-to) | 642-649 |
| Number of pages | 8 |
| Journal | Brain |
| Volume | 126 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2003 |
| Externally published | Yes |
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Keywords
- Autosomal recessive
- Charcot-Marie-Tooth neuropathy
- Ganglioside-induced differentiation-associated protein-1
- GDAP1
- Hereditary motor and sensory neuropathy
- Intermediate
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Mutations in the ganglioside-induced differentiation-associated protein-1 (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth neuropathy. / Senderek, Jan; Bergmann, Carsten; Ramaekers, Vincent T.; Nelis, Eva; Bernert, Günther; Makowski, Astrid; Zuchner, Stephan L; De Jonghe, Peter; Rudnik-Schöneborn, Sabine; Zerres, Klaus; Schröder, J. Michael.
In: Brain, Vol. 126, No. 3, 01.03.2003, p. 642-649.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mutations in the ganglioside-induced differentiation-associated protein-1 (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth neuropathy
AU - Senderek, Jan
AU - Bergmann, Carsten
AU - Ramaekers, Vincent T.
AU - Nelis, Eva
AU - Bernert, Günther
AU - Makowski, Astrid
AU - Zuchner, Stephan L
AU - De Jonghe, Peter
AU - Rudnik-Schöneborn, Sabine
AU - Zerres, Klaus
AU - Schröder, J. Michael
PY - 2003/3/1
Y1 - 2003/3/1
N2 - Mutations in the gene for the ganglioside-induced differentiation-associated protein-1 (GDAP1) on 8q21 recently were reported to cause autosomal recessive Charcot-Marie-Tooth (CMT) sensorimotor neuropathy. Neurophysiology and nerve pathology were heterogeneous in these cases: a subset of GDAP1 mutations was associated with peripheral nerve demyelination, whereas others resulted in axonal degeneration. In this study, we identified two novel mutations disrupting the GDAP1 reading frame. Homozygosity for a single base pair insertion in exon 3 (c.349_350insT) was observed in affected children from a Turkish inbred pedigree. The other novel allele detected in a German patient was a homozygous mutation of the intron 4 donor splice site (c.579 + 1G>A). Patients with GDAP1 mutations displayed severe, early childhood-onset CMT neuropathy with prominent pes equinovarus deformity and impairment of hand muscles. Nerve conduction velocities were between 25 and 35 m/s and peripheral nerve pathology showed axonal as well as demyelinating changes. These findings fitted the definition of intermediate type CMT and further support the view that GDAP1 is vital for both, axonal integrity and Schwann cell properties.
AB - Mutations in the gene for the ganglioside-induced differentiation-associated protein-1 (GDAP1) on 8q21 recently were reported to cause autosomal recessive Charcot-Marie-Tooth (CMT) sensorimotor neuropathy. Neurophysiology and nerve pathology were heterogeneous in these cases: a subset of GDAP1 mutations was associated with peripheral nerve demyelination, whereas others resulted in axonal degeneration. In this study, we identified two novel mutations disrupting the GDAP1 reading frame. Homozygosity for a single base pair insertion in exon 3 (c.349_350insT) was observed in affected children from a Turkish inbred pedigree. The other novel allele detected in a German patient was a homozygous mutation of the intron 4 donor splice site (c.579 + 1G>A). Patients with GDAP1 mutations displayed severe, early childhood-onset CMT neuropathy with prominent pes equinovarus deformity and impairment of hand muscles. Nerve conduction velocities were between 25 and 35 m/s and peripheral nerve pathology showed axonal as well as demyelinating changes. These findings fitted the definition of intermediate type CMT and further support the view that GDAP1 is vital for both, axonal integrity and Schwann cell properties.
KW - Autosomal recessive
KW - Charcot-Marie-Tooth neuropathy
KW - Ganglioside-induced differentiation-associated protein-1
KW - GDAP1
KW - Hereditary motor and sensory neuropathy
KW - Intermediate
UR - http://www.scopus.com/inward/record.url?scp=0037370916&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037370916&partnerID=8YFLogxK
U2 - 10.1093/brain/awg068
DO - 10.1093/brain/awg068
M3 - Article
VL - 126
SP - 642
EP - 649
JO - Brain
JF - Brain
SN - 0006-8950
IS - 3
ER -