Autosomal dominant spastic paraplegias

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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 (n=1), SPG8 (n=2), SPG9A (n=1), SPG12 (n=1), SPG17 (n=3), SPG31 (n=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 de novo mutation p.Gly106Arg in NIPA1 (SPG6), the earlier reported mutation p.Val626Phe in WASHC5 (SPG8) in isolated case and the novel p.Val695Ala in WASHC5 (SPG8) in a family with 4 patients, the novel mutation p.Thr301Arg in RTN2 (SPG12) in a family with 2 patients, the novel mutation c.105+4A>G in REEP1 (SPG31) in a family with 4 patients and the reported earlier p.Lys101Lys in REEP1 (SPG31) in a family with 3 patients, the known de novo mutation p.Arg252Gln in ALDH18A1 (SPG9A) in two monozygous twins; the common mutation p.Ser90Leu in BSCL2 (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.

Keywords:

spastic paraplegias

SPG6

SPG8

SPG9A

SPG12

SPG17

SPG31

mutations

massive parallel sequencing (MPS)

phenotypes

Authors:

Rudenskaya G.E.

Bochkov Research Centre for Medical Genetics

ORCID: 0000-0002-8244-9367

Kadnikova V.A.

Bochkov Research Centre for Medical Genetics

ORCID: 0000-0002-1245-4881

Bessonova L.A.

Bochkov Research Center for Medical Genetics

Sparber P.A.

Bochkov Research Center for Medical Genetics

Kurbatov S.A.

Voronezh Regional Clinical Consultative and Diagnostic Center

Mironovich O.L.

Research Centre for Medical Genetics

Konovalov F.A.

Genomed LLC, Laboratory of Clinical Bioinformatics

Ryzhkova O.P.

Bochkov Research Centre for Medical Genetics

ORCID: 0000-0003-1285-9093

Received:

31.07.2020

Accepted:

20.09.2020

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