[Autosomal dominant spastic paraplegias].

OBJECTIVE

To estimate the proportion and spectrum of infrequent autosomal dominant spastic paraplegias in a group of families with DNA-confirmed diagnosis and to investigate their molecular and clinical characteristics.

MATERIAL AND METHODS

Ten families with 6 AD-SPG: SPG6 (=1), SPG8 (=2), SPG9A (=1), SPG12 (=1), SPG17 (=3), SPG31 (=2) were studied using clinical, genealogical, molecular-genetic (massive parallel sequencing, spastic paraplegia panel, whole-exome sequencing, multiplex ligation-dependent amplification, Sanger sequencing) and bioinformatic methods.

RESULTS AND CONCLUSION

Nine heterozygous mutations were detected in 6 genes, including the common mutation p.Gly106Arg in (SPG6), the earlier reported mutation p.Val626Phe in WASHC5 (SPG8) in isolated case and the novel p.Val695Ala in (SPG8) in a family with 4 patients, the novel mutation p.Thr301Arg in (SPG12) in a family with 2 patients, the novel mutation c.105+4A>G in (SPG31) in a family with 4 patients and the reported earlier p.Lys101Lys in (SPG31) in a family with 3 patients, the known mutation p.Arg252Gln in (SPG9A) in two monozygous twins; the common mutation p.Ser90Leu in (SPG17) in a family with 3 patients and in isolated case, reported mutation p.Leu363Pro in a family with 2 patients. SPG6, SPG8, SPG12 and SPG31 presented 'pure' phenotypes, SPG31 had most benign course. Age of onset varied in SPG31 family and was atypically early in SPG6 case. Patients with SPG9A and SPG17 had 'complicated' paraplegias; amyotrophy of hands typical for SPG17 was absent in a child and in an adolescent from 2 families, but may develop later.