Atlastin1 Mutations Are Frequent in Young-Onset Autosomal Dominant Spastic Paraplegia

Abstract

This study enables us to estimate the frequency of the SPG3A mutations in France at 39% in families with young-onset autosomal dominant spastic paraplegia after exclusion of SPG4 cases. So far, most mutations have been private, although they were all found in exons 7, 8, 12, and 13. These exons should be given priority when performing molecular diagnoses for SPG3A.

Characterization of a novel SPG3A deletion in a French‐Canadian family

“…The clinical picture associated with the p.del436N mutation is an early‐onset, slowly progressive form of pure HSP. This clinical description closely matches those associated with other SPG3A mutations 8, 10, 20. Incomplete penetrance (eg, Subject R29239) has been reported previously, most strikingly for the R415W mutation where several carriers were clinically normal 11, 14…”

Characterization of a novel SPG3A deletion in a French‐Canadian family

“…The clinical picture associated with the p.del436N mutation is an early‐onset, slowly progressive form of pure HSP. This clinical description closely matches those associated with other SPG3A mutations 8, 10, 20. Incomplete penetrance (eg, Subject R29239) has been reported previously, most strikingly for the R415W mutation where several carriers were clinically normal 11, 14…”

Mutation and Clinical Characteristics of Autosomal-Dominant Hereditary Spastic Paraplegias in China

“…S3); 1 mutation, c.715C>T (p.N102S), was identified in an apparently sporadic case (1/66, 1.5%). All three ATL1 mutations found in this cohort had been previously reported in other research groups [21,22,23,24,25]; 1 reported mutation, c.316G>C, in NIPA1 was detected in an AD-HSP family M3196 (1/54, 1.8%; table 1). Detailed information about this family has been previously reported by our group [26].…”

Disease‐Causing Variants in the ATL1 Gene Are a Rare Cause of Hereditary Spastic Paraplegia among Czech Patients

“…Although variants in the ATL1 gene were previously repeatedly described as a frequent cause of HSP, in approximately 10 % of all HSP patients (Fink et al., ; Durr et al., ), and the most common cause of early‐onset HSP, accounting for up to 50% of all AD HSP with onset before the age of 10 years (Abel et al., ; Namekawa et al., ; Polymeris et al., ), our results show significantly lower frequencies among Czech HSP patients. In the whole group of patients, we found only 4.3% patients with possibly causal variants in the ATL1 gene and in only 11.1% of patients with onset before the age of 10 years.…”

Characterization of a novel SPG3A deletion in a French‐Canadian family

“…The clinical picture associated with the p.del436N mutation is an early‐onset, slowly progressive form of pure HSP. This clinical description closely matches those associated with other SPG3A mutations 8, 10, 20. Incomplete penetrance (eg, Subject R29239) has been reported previously, most strikingly for the R415W mutation where several carriers were clinically normal 11, 14…”

Mutation and Clinical Characteristics of Autosomal-Dominant Hereditary Spastic Paraplegias in China

“…S3); 1 mutation, c.715C>T (p.N102S), was identified in an apparently sporadic case (1/66, 1.5%). All three ATL1 mutations found in this cohort had been previously reported in other research groups [21,22,23,24,25]; 1 reported mutation, c.316G>C, in NIPA1 was detected in an AD-HSP family M3196 (1/54, 1.8%; table 1). Detailed information about this family has been previously reported by our group [26].…”

Disease‐Causing Variants in the ATL1 Gene Are a Rare Cause of Hereditary Spastic Paraplegia among Czech Patients

“…Although variants in the ATL1 gene were previously repeatedly described as a frequent cause of HSP, in approximately 10 % of all HSP patients (Fink et al., ; Durr et al., ), and the most common cause of early‐onset HSP, accounting for up to 50% of all AD HSP with onset before the age of 10 years (Abel et al., ; Namekawa et al., ; Polymeris et al., ), our results show significantly lower frequencies among Czech HSP patients. In the whole group of patients, we found only 4.3% patients with possibly causal variants in the ATL1 gene and in only 11.1% of patients with onset before the age of 10 years.…”

Characterization of a novel SPG3A deletion in a French‐Canadian family

“…The clinical picture associated with the p.del436N mutation is an early‐onset, slowly progressive form of pure HSP. This clinical description closely matches those associated with other SPG3A mutations 8, 10, 20. Incomplete penetrance (eg, Subject R29239) has been reported previously, most strikingly for the R415W mutation where several carriers were clinically normal 11, 14…”

Mutation and Clinical Characteristics of Autosomal-Dominant Hereditary Spastic Paraplegias in China

“…S3); 1 mutation, c.715C>T (p.N102S), was identified in an apparently sporadic case (1/66, 1.5%). All three ATL1 mutations found in this cohort had been previously reported in other research groups [21,22,23,24,25]; 1 reported mutation, c.316G>C, in NIPA1 was detected in an AD-HSP family M3196 (1/54, 1.8%; table 1). Detailed information about this family has been previously reported by our group [26].…”

Disease‐Causing Variants in the ATL1 Gene Are a Rare Cause of Hereditary Spastic Paraplegia among Czech Patients

“…Although variants in the ATL1 gene were previously repeatedly described as a frequent cause of HSP, in approximately 10 % of all HSP patients (Fink et al., ; Durr et al., ), and the most common cause of early‐onset HSP, accounting for up to 50% of all AD HSP with onset before the age of 10 years (Abel et al., ; Namekawa et al., ; Polymeris et al., ), our results show significantly lower frequencies among Czech HSP patients. In the whole group of patients, we found only 4.3% patients with possibly causal variants in the ATL1 gene and in only 11.1% of patients with onset before the age of 10 years.…”