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Genetics of motor neuron diseases 05 November 2004
AD = autosomal dominant; AR = autosomal recessive; XD = X-linked dominant; XR = X-linked recessive; FTD = frontotemporal dementia; SMA = spinal muscular atrophy; HMN = hereditary motor neuronopathy;ALS-PDC = ALS-Parkinson-Dementia Complex of Guam.
Genetic mechanisms in three motor neuron diseases. (A) Familial ALS (FALS). Over 80 different mutations of the SOD1 gene may account for the disease. These may be single base substitutions, insertions, and deletions, missense and nonsense. They are present in all five exons and also in intron 4. Most mutations are heterozygote, with the homozygote form found in Finland and Sweden. (B) Spinal muscular atrophy (SMA). In SMA, there are two copies of the SMN (survival motor neuron), NAIP (neuronal apoptosis inhibitory polypeptide), and p44c genes. In this condition, the telomeric copy of SMN, SMNT, is deleted or converted to SMNC. The NAIP and p44c genes may also be mutant. (C) Spinobulbar muscular atrophy (SBMA). In SBMA, there is an expansion of the CAG (polyglutamine) repeat region within exon 1 of the androgen receptor gene. In a normal individual, the number of repeats is 10 to 36, and in SBMA it is expanded to 40 to 62.
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