Mutations of the ANG Gene in French Patients With Sporadic Amyotrophic Lateral Sclerosis

Abstract

Background: Mutations in the angiogenin gene, ANG, have been associated recently with familial and sporadic forms of amyotrophic lateral sclerosis (ALS). However, the cellular and molecular mechanisms that link ANG, a multidomain protein, to ALS are still unknown.Objective: To assess the frequency of ANG gene mutations in 855 French patients with sporadic ALS. Design: We analyzed by direct sequencing the full coding region of the ANG gene in a cohort of French patients with sporadic ALS. The clinical characteristics of patients carrying ANG mutations are detailed. Setting: French ALS Study Group. Patients: A total of 855 patients with sporadic ALS. Main Outcome Measures: Results of genetic analyses.

Exome Sequencing of a Portuguese Cohort of Frontotemporal Dementia Patients: Looking Into the ALS-FTD Continuum

“…Interestingly, in an ALS-FTD cohort, the levels of angiogenin in CSF were only elevated in patients with FTD ( 40 ) and at least one patient reported in the literature seemed to have ALS-FTD ( 42 ). The variant we identified (p.Gly123Ala) is located close to the previously reported variants p.Arg121His and p.Arg122His ( 43 , 44 ). The patient carrying this variant is part of a family with 3 of 4 siblings affected, and this variant was only present in two of them.…”

Exome Sequencing of a Portuguese Cohort of Frontotemporal Dementia Patients: Looking Into the ALS-FTD Continuum

“…Interestingly, in an ALS-FTD cohort, the levels of angiogenin in CSF were only elevated in patients with FTD ( 40 ) and at least one patient reported in the literature seemed to have ALS-FTD ( 42 ). The variant we identified (p.Gly123Ala) is located close to the previously reported variants p.Arg121His and p.Arg122His ( 43 , 44 ). The patient carrying this variant is part of a family with 3 of 4 siblings affected, and this variant was only present in two of them.…”

SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral sclerosis: genotype–phenotype correlations

“…The K17I mutation has been reported in three apparently healthy people,4 17 but was not detected in our 500 controls. We also found the c.232A→G/p.Lys78Glu (K54E) and the c.434G→A/p.Arg145His (R121H) variants in two FALS, which were previously reported as mutations in sporadic ALS (SALS) 17 18. In the present study, however, these substitutions were not detected in the other affected relatives.…”

Identification of novel Angiogenin (ANG) gene missense variants in German patients with amyotrophic lateral sclerosis

“…Both ANG missense variants are novel and, to our knowledge, have not been previously documented. The variants F(−13)L and K54E appear to be disease-specific in our population, since both were absent in our 616 controls, as well as in 3107 controls that were sequenced in previous ANG mutational screenings [4–7, 9, 18, 22, 23]. Our results indicate that the novel ANG missense variants F(−13)L and K54E are linked to ALS in the German population.…”

“…However, segregation of ANG missense variants has not been fully reproduced in other populations [5, 7, 18, 23] until the recent screening of a Dutch pedigree carrying the K17I missense variant [22]. In our case, the carriers of the ANG missense variants F(−13)L and K54E were apparently ‘sporadic’ ALS cases without a family history of ALS.…”

Exome Sequencing of a Portuguese Cohort of Frontotemporal Dementia Patients: Looking Into the ALS-FTD Continuum

“…Interestingly, in an ALS-FTD cohort, the levels of angiogenin in CSF were only elevated in patients with FTD ( 40 ) and at least one patient reported in the literature seemed to have ALS-FTD ( 42 ). The variant we identified (p.Gly123Ala) is located close to the previously reported variants p.Arg121His and p.Arg122His ( 43 , 44 ). The patient carrying this variant is part of a family with 3 of 4 siblings affected, and this variant was only present in two of them.…”

SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral sclerosis: genotype–phenotype correlations

“…The K17I mutation has been reported in three apparently healthy people,4 17 but was not detected in our 500 controls. We also found the c.232A→G/p.Lys78Glu (K54E) and the c.434G→A/p.Arg145His (R121H) variants in two FALS, which were previously reported as mutations in sporadic ALS (SALS) 17 18. In the present study, however, these substitutions were not detected in the other affected relatives.…”

Identification of novel Angiogenin (ANG) gene missense variants in German patients with amyotrophic lateral sclerosis

“…Both ANG missense variants are novel and, to our knowledge, have not been previously documented. The variants F(−13)L and K54E appear to be disease-specific in our population, since both were absent in our 616 controls, as well as in 3107 controls that were sequenced in previous ANG mutational screenings [4–7, 9, 18, 22, 23]. Our results indicate that the novel ANG missense variants F(−13)L and K54E are linked to ALS in the German population.…”

“…However, segregation of ANG missense variants has not been fully reproduced in other populations [5, 7, 18, 23] until the recent screening of a Dutch pedigree carrying the K17I missense variant [22]. In our case, the carriers of the ANG missense variants F(−13)L and K54E were apparently ‘sporadic’ ALS cases without a family history of ALS.…”

Exome Sequencing of a Portuguese Cohort of Frontotemporal Dementia Patients: Looking Into the ALS-FTD Continuum

“…Interestingly, in an ALS-FTD cohort, the levels of angiogenin in CSF were only elevated in patients with FTD ( 40 ) and at least one patient reported in the literature seemed to have ALS-FTD ( 42 ). The variant we identified (p.Gly123Ala) is located close to the previously reported variants p.Arg121His and p.Arg122His ( 43 , 44 ). The patient carrying this variant is part of a family with 3 of 4 siblings affected, and this variant was only present in two of them.…”

SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral sclerosis: genotype–phenotype correlations

“…The K17I mutation has been reported in three apparently healthy people,4 17 but was not detected in our 500 controls. We also found the c.232A→G/p.Lys78Glu (K54E) and the c.434G→A/p.Arg145His (R121H) variants in two FALS, which were previously reported as mutations in sporadic ALS (SALS) 17 18. In the present study, however, these substitutions were not detected in the other affected relatives.…”

Identification of novel Angiogenin (ANG) gene missense variants in German patients with amyotrophic lateral sclerosis

“…Both ANG missense variants are novel and, to our knowledge, have not been previously documented. The variants F(−13)L and K54E appear to be disease-specific in our population, since both were absent in our 616 controls, as well as in 3107 controls that were sequenced in previous ANG mutational screenings [4–7, 9, 18, 22, 23]. Our results indicate that the novel ANG missense variants F(−13)L and K54E are linked to ALS in the German population.…”

“…However, segregation of ANG missense variants has not been fully reproduced in other populations [5, 7, 18, 23] until the recent screening of a Dutch pedigree carrying the K17I missense variant [22]. In our case, the carriers of the ANG missense variants F(−13)L and K54E were apparently ‘sporadic’ ALS cases without a family history of ALS.…”