Objective: To systemically screen some common spastic paraplegia genes (SPG) in the Taiwanese patients with apparently sporadic pure spastic paraplegia.

Background: Hereditary spastic paraplegias (HSP) are a heterogeneous group of degenerative disorders of the spinal cord characterized by progressive spasticity and weakness of the lower limbs. HSPs are among most heterogeneous Mendelian disease including autosomal dominant, autosomal recessive, and X-linked modes of inheritance. There are at least 83 HSP loci and 68 SPG identified. Moreover, almost half of all cases are apparently sporadic and the studies on the genetic background in these cases are quite rare.

Methods: Systemic screening of the SPG3A (ATL1), SPG4 (SPAST), SPG5 (CYP7B1), SPG7, and SPG 31 (REEP1) was performed in a cohort of 28 Taiwanese patients with apparently sporadic pure spastic paraplegia. Clinical characteristics were further analyzed in the genetically confirmed patients.

Results: In our cohort, this protocol enables the identification of a genetic cause in 15 (53%) apparently sporadic cases. SPAST mutation, the most common subtype of HSP, has been found in seven (25%) of our sporadic HSP cases. Mutations in ATL1, and CYP7B1 occur in four (14%) and four (14%) respectively and other cases remain genetically unresolved. SPG5 is characterized by rather severe dorsal column involvement with profound sensory deficits of vibration and joint position in the lower limbs. For those with SPAST mutations, there is a variable age at onset ranging from childhood to the 5th decade, with a mean age at onset of 31.3 ± 14.5 years. However, cases with ATL1 mutation typically present as toddler onset with very slow progression. After the familial genetic survey, reduced penetrance and de novo mutations may explain the lack of positive families in some of HSP cases.

Conclusions: Apparently sporadic patients without a positive family history of HSP still need to be surveyed for possible disease-causing SPG mutations. The phenotypes in these genetically confirmed patients are similar to previously described in familial cases with inherited mutations. The whole-exome sequencing and panel SPG genes testing may be used for the further identification of inheritance pattern in the genetically unresolved cases.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-genetic-analyses-in-a-cohort-of-the-taiwanese-patients-with-apparently-sporadic-pure-spastic-paraplegia/