Submission Details

Submitter:

Classification:
Definitive
GENCC:100001
Gene:
Disease:
Troyer syndrome
Mode Of Inheritance:
Autosomal recessive
Evaluated Date:
12/19/2022
Evidence/Notes:

SPART was first reported in relation to Troyer Syndrome in 2002 in the Old Order Amish population (PMIDs:6022528, 12134148). Troyer Syndrome is an autosomal recessive form of complicated spastic paraplegia, typically with onset between the ages of 1-2 years. Affected individuals present with short stature, distal amyotrophy, dysarthria, and mild cognitive defects (Patel et al., PMID:12134148). At least 7 unique variants have been reported in 70 individuals, including one founder mutation (PMIDs: 12134148, 20437587, 31314595, 27539578). The molecular mechanism appears to be loss of function. Experimentally, the gene-disease relationship is supported by biochemical assays, in vitro studies, a mouse model that partially recapitulates the human phenotype (PMID:19307600, PMID: 20719964), and rescue experiments in C. elegans (PMID: 26114733). In summary, there is definitive evidence to support the relationship between SPART and autosomal recessive Troyer Syndrome. This relationship has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. The Cerebral Palsy Expert panel approved the classification on December 19, 2022 (SOP version 9).

PubMed IDs:
18413476 20437587 22619377 26114733 28679690 31314595 32661208
Public Report:
Assertion Criteria:
Submitter Submitted Date:
12/05/2025

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