Spinal and bulbar muscular atrophy (SBMA) is a lower motor neuron disease caused by the expansion of a trinucleotide CAG repeat in the androgen receptor (AR) gene.
The analysis of white matter structural connectivity by regional FA reductions demonstrated the characteristic alteration patterns along the CST and also in frontal and prefrontal brain areas in LMND patients compared to controls and ALS.
The analysis of white matter structural connectivity by regional FA reductions demonstrated the characteristic alteration patterns along the CST and also in frontal and prefrontal brain areas in LMND patients compared to controls and ALS.
Previously, mutations in DCTN1 were identified in a family with lower motor neuron disease, in amyotrophic lateral sclerosis (ALS), and in a family with ALS/frontotemporal dementia (FTD), suggesting a central role for DCTN1 in neurodegeneration.
Interestingly, this mutation causing a loss-of-function of HSJ1 is linked to a pure lower motor neuron disease, strongly suggesting that HSJ1 also plays an important and specific role in motor neurons.
The analysis of white matter structural connectivity by regional FA reductions demonstrated the characteristic alteration patterns along the CST and also in frontal and prefrontal brain areas in LMND patients compared to controls and ALS.
Mutations in the Pleckstrin homology domain-containing, family G member 5 (PLEKHG5) gene has been reported in a family harboring an autosomal recessive lower motor neuron disease (LMND).
Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cells.
The analysis of white matter structural connectivity by regional FA reductions demonstrated the characteristic alteration patterns along the CST and also in frontal and prefrontal brain areas in LMND patients compared to controls and ALS.
We searched for deletions of SMN1 and SMN2 in a group of 11 patients with sporadic adult-onset lower motor neuron disease (also referred to as "progressive muscular atrophy") and found an excess of patients carrying homozygous deletions of SMN2 exon 7 (36% versus 5% in the normal population).
A rare syndrome characterized by lower motor neuron disease associated with progressive myoclonic epilepsy, referred to as "spinal muscular atrophy associated with progressive myoclonic epilepsy" (SMA-PME), has been described in childhood and is inherited as an autosomal recessive trait.
A rare variant with associated myoclonic epilepsy and lower motor neuron disease had been previously described in three families before the SMN gene, responsible for the common form of SMA, was isolated.
Homozygous SMN1 (survival motor neuron) gene deletion causes spinal muscular atrophy, and SMN2 gene deletions are possible risk factors in lower motor neuron disease.
We consider that this case represents a previously unrecognized type of lower motor neuron disease that resulted from homozygous deletion of the SMN2 gene.