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Abstract
Discussion Forum (0)
A Novel Variant In CADM3 Causes Charcot-Marie-Tooth Type 2FF In A Malian Family
Poster No: 1297
Presenter: Abdoulaye Yalcouy©
Institution: University of Sciences Techniques and Technologies of Bamako
Introduction: Charcot-Marie-Tooth disease type 2FF caused by CADM3 variants was recently reported in three Caucasian families. We report here a novel variant in CADM3 in a Malian family with CMT
Methods: A careful clinical examination, and nerve conduction studies (NCS) were done. DNA was extracted from peripheral blood. CMT gene panel (50 genes + PMP22 duplication) testing and Whole Exome Sequencing (WES) were performed. Putative variant was confirmed through Sanger sequencing and segregation analysis was done. Western blot and Immunofluorescence analysis were performed.
Results: Seven patients (six males and one female) and their unaffected relatives from a large family were enrolled. The disease distribution was consistent with an autosomal dominant inheritance pattern. The mean age at diagnosis was 35.7 years, ranging from 12 to 65 years, and walking difficulty was the most common starting symptom. Neurological examination showed a distal muscle weakness and wasting, steppage gait, absent reflexes, mild sensory loss, and pes cavus. A high clinical variability was noted, but overall, symptoms were more pronounced in the upper limbs compared to the lower limbs. NCS were performed in four individuals and were consistent with an axonal-type neuropathy with marked motor involvement. CMT gene panel testing was first done and was negative. However, WES revealed a novel pathogenic missense variant at position c.1102G>T (Gly368Cys) in CADM3, segregating with the disease in the family. In addition, Western blot and Immunofluorescence analysis showed a significant decrease in the levels of CADM3-Gly368Cys mutant protein in the membrane and suggest that the new cysteine might interfere with the native disulfide bond important for the formation of the Ig-like loops.
Conclusions: We report a novel variant in CADM3, and provide further evidence of its implication in axonal-type CMT. A large collaborative study including patients from different genetic backgrounds may unveil several novel CMT genes or variants and inform the disease mechanism
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support: NIH Grant U01HG007044
Keywords: CMT, Next generation sequencing, CADM3, Novel variant, Mali
Poster No: 1297
Presenter: Abdoulaye Yalcouy©
Institution: University of Sciences Techniques and Technologies of Bamako
Introduction: Charcot-Marie-Tooth disease type 2FF caused by CADM3 variants was recently reported in three Caucasian families. We report here a novel variant in CADM3 in a Malian family with CMT
Methods: A careful clinical examination, and nerve conduction studies (NCS) were done. DNA was extracted from peripheral blood. CMT gene panel (50 genes + PMP22 duplication) testing and Whole Exome Sequencing (WES) were performed. Putative variant was confirmed through Sanger sequencing and segregation analysis was done. Western blot and Immunofluorescence analysis were performed.
Results: Seven patients (six males and one female) and their unaffected relatives from a large family were enrolled. The disease distribution was consistent with an autosomal dominant inheritance pattern. The mean age at diagnosis was 35.7 years, ranging from 12 to 65 years, and walking difficulty was the most common starting symptom. Neurological examination showed a distal muscle weakness and wasting, steppage gait, absent reflexes, mild sensory loss, and pes cavus. A high clinical variability was noted, but overall, symptoms were more pronounced in the upper limbs compared to the lower limbs. NCS were performed in four individuals and were consistent with an axonal-type neuropathy with marked motor involvement. CMT gene panel testing was first done and was negative. However, WES revealed a novel pathogenic missense variant at position c.1102G>T (Gly368Cys) in CADM3, segregating with the disease in the family. In addition, Western blot and Immunofluorescence analysis showed a significant decrease in the levels of CADM3-Gly368Cys mutant protein in the membrane and suggest that the new cysteine might interfere with the native disulfide bond important for the formation of the Ig-like loops.
Conclusions: We report a novel variant in CADM3, and provide further evidence of its implication in axonal-type CMT. A large collaborative study including patients from different genetic backgrounds may unveil several novel CMT genes or variants and inform the disease mechanism
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support: NIH Grant U01HG007044
Keywords: CMT, Next generation sequencing, CADM3, Novel variant, Mali
A Novel Variant In CADM3 Causes Charcot-Marie-Tooth Type 2FF In A Malian Family
Poster No: 1297
Presenter: Abdoulaye Yalcouy©
Institution: University of Sciences Techniques and Technologies of Bamako
Introduction: Charcot-Marie-Tooth disease type 2FF caused by CADM3 variants was recently reported in three Caucasian families. We report here a novel variant in CADM3 in a Malian family with CMT
Methods: A careful clinical examination, and nerve conduction studies (NCS) were done. DNA was extracted from peripheral blood. CMT gene panel (50 genes + PMP22 duplication) testing and Whole Exome Sequencing (WES) were performed. Putative variant was confirmed through Sanger sequencing and segregation analysis was done. Western blot and Immunofluorescence analysis were performed.
Results: Seven patients (six males and one female) and their unaffected relatives from a large family were enrolled. The disease distribution was consistent with an autosomal dominant inheritance pattern. The mean age at diagnosis was 35.7 years, ranging from 12 to 65 years, and walking difficulty was the most common starting symptom. Neurological examination showed a distal muscle weakness and wasting, steppage gait, absent reflexes, mild sensory loss, and pes cavus. A high clinical variability was noted, but overall, symptoms were more pronounced in the upper limbs compared to the lower limbs. NCS were performed in four individuals and were consistent with an axonal-type neuropathy with marked motor involvement. CMT gene panel testing was first done and was negative. However, WES revealed a novel pathogenic missense variant at position c.1102G>T (Gly368Cys) in CADM3, segregating with the disease in the family. In addition, Western blot and Immunofluorescence analysis showed a significant decrease in the levels of CADM3-Gly368Cys mutant protein in the membrane and suggest that the new cysteine might interfere with the native disulfide bond important for the formation of the Ig-like loops.
Conclusions: We report a novel variant in CADM3, and provide further evidence of its implication in axonal-type CMT. A large collaborative study including patients from different genetic backgrounds may unveil several novel CMT genes or variants and inform the disease mechanism
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support: NIH Grant U01HG007044
Keywords: CMT, Next generation sequencing, CADM3, Novel variant, Mali
Poster No: 1297
Presenter: Abdoulaye Yalcouy©
Institution: University of Sciences Techniques and Technologies of Bamako
Introduction: Charcot-Marie-Tooth disease type 2FF caused by CADM3 variants was recently reported in three Caucasian families. We report here a novel variant in CADM3 in a Malian family with CMT
Methods: A careful clinical examination, and nerve conduction studies (NCS) were done. DNA was extracted from peripheral blood. CMT gene panel (50 genes + PMP22 duplication) testing and Whole Exome Sequencing (WES) were performed. Putative variant was confirmed through Sanger sequencing and segregation analysis was done. Western blot and Immunofluorescence analysis were performed.
Results: Seven patients (six males and one female) and their unaffected relatives from a large family were enrolled. The disease distribution was consistent with an autosomal dominant inheritance pattern. The mean age at diagnosis was 35.7 years, ranging from 12 to 65 years, and walking difficulty was the most common starting symptom. Neurological examination showed a distal muscle weakness and wasting, steppage gait, absent reflexes, mild sensory loss, and pes cavus. A high clinical variability was noted, but overall, symptoms were more pronounced in the upper limbs compared to the lower limbs. NCS were performed in four individuals and were consistent with an axonal-type neuropathy with marked motor involvement. CMT gene panel testing was first done and was negative. However, WES revealed a novel pathogenic missense variant at position c.1102G>T (Gly368Cys) in CADM3, segregating with the disease in the family. In addition, Western blot and Immunofluorescence analysis showed a significant decrease in the levels of CADM3-Gly368Cys mutant protein in the membrane and suggest that the new cysteine might interfere with the native disulfide bond important for the formation of the Ig-like loops.
Conclusions: We report a novel variant in CADM3, and provide further evidence of its implication in axonal-type CMT. A large collaborative study including patients from different genetic backgrounds may unveil several novel CMT genes or variants and inform the disease mechanism
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support: NIH Grant U01HG007044
Keywords: CMT, Next generation sequencing, CADM3, Novel variant, Mali
A Novel Variant In CADM3 Causes Charcot-Marie-Tooth Type 2FF In A Malian Family
Dr. Abdoulaye Yalcouyé
Abstract
Discussion Forum (0)
A Novel Variant In CADM3 Causes Charcot-Marie-Tooth Type 2FF In A Malian Family
Poster No: 1297
Presenter: Abdoulaye Yalcouy©
Institution: University of Sciences Techniques and Technologies of Bamako
Introduction: Charcot-Marie-Tooth disease type 2FF caused by CADM3 variants was recently reported in three Caucasian families. We report here a novel variant in CADM3 in a Malian family with CMT
Methods: A careful clinical examination, and nerve conduction studies (NCS) were done. DNA was extracted from peripheral blood. CMT gene panel (50 genes + PMP22 duplication) testing and Whole Exome Sequencing (WES) were performed. Putative variant was confirmed through Sanger sequencing and segregation analysis was done. Western blot and Immunofluorescence analysis were performed.
Results: Seven patients (six males and one female) and their unaffected relatives from a large family were enrolled. The disease distribution was consistent with an autosomal dominant inheritance pattern. The mean age at diagnosis was 35.7 years, ranging from 12 to 65 years, and walking difficulty was the most common starting symptom. Neurological examination showed a distal muscle weakness and wasting, steppage gait, absent reflexes, mild sensory loss, and pes cavus. A high clinical variability was noted, but overall, symptoms were more pronounced in the upper limbs compared to the lower limbs. NCS were performed in four individuals and were consistent with an axonal-type neuropathy with marked motor involvement. CMT gene panel testing was first done and was negative. However, WES revealed a novel pathogenic missense variant at position c.1102G>T (Gly368Cys) in CADM3, segregating with the disease in the family. In addition, Western blot and Immunofluorescence analysis showed a significant decrease in the levels of CADM3-Gly368Cys mutant protein in the membrane and suggest that the new cysteine might interfere with the native disulfide bond important for the formation of the Ig-like loops.
Conclusions: We report a novel variant in CADM3, and provide further evidence of its implication in axonal-type CMT. A large collaborative study including patients from different genetic backgrounds may unveil several novel CMT genes or variants and inform the disease mechanism
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support: NIH Grant U01HG007044
Keywords: CMT, Next generation sequencing, CADM3, Novel variant, Mali
Poster No: 1297
Presenter: Abdoulaye Yalcouy©
Institution: University of Sciences Techniques and Technologies of Bamako
Introduction: Charcot-Marie-Tooth disease type 2FF caused by CADM3 variants was recently reported in three Caucasian families. We report here a novel variant in CADM3 in a Malian family with CMT
Methods: A careful clinical examination, and nerve conduction studies (NCS) were done. DNA was extracted from peripheral blood. CMT gene panel (50 genes + PMP22 duplication) testing and Whole Exome Sequencing (WES) were performed. Putative variant was confirmed through Sanger sequencing and segregation analysis was done. Western blot and Immunofluorescence analysis were performed.
Results: Seven patients (six males and one female) and their unaffected relatives from a large family were enrolled. The disease distribution was consistent with an autosomal dominant inheritance pattern. The mean age at diagnosis was 35.7 years, ranging from 12 to 65 years, and walking difficulty was the most common starting symptom. Neurological examination showed a distal muscle weakness and wasting, steppage gait, absent reflexes, mild sensory loss, and pes cavus. A high clinical variability was noted, but overall, symptoms were more pronounced in the upper limbs compared to the lower limbs. NCS were performed in four individuals and were consistent with an axonal-type neuropathy with marked motor involvement. CMT gene panel testing was first done and was negative. However, WES revealed a novel pathogenic missense variant at position c.1102G>T (Gly368Cys) in CADM3, segregating with the disease in the family. In addition, Western blot and Immunofluorescence analysis showed a significant decrease in the levels of CADM3-Gly368Cys mutant protein in the membrane and suggest that the new cysteine might interfere with the native disulfide bond important for the formation of the Ig-like loops.
Conclusions: We report a novel variant in CADM3, and provide further evidence of its implication in axonal-type CMT. A large collaborative study including patients from different genetic backgrounds may unveil several novel CMT genes or variants and inform the disease mechanism
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support: NIH Grant U01HG007044
Keywords: CMT, Next generation sequencing, CADM3, Novel variant, Mali
A Novel Variant In CADM3 Causes Charcot-Marie-Tooth Type 2FF In A Malian Family
Poster No: 1297
Presenter: Abdoulaye Yalcouy©
Institution: University of Sciences Techniques and Technologies of Bamako
Introduction: Charcot-Marie-Tooth disease type 2FF caused by CADM3 variants was recently reported in three Caucasian families. We report here a novel variant in CADM3 in a Malian family with CMT
Methods: A careful clinical examination, and nerve conduction studies (NCS) were done. DNA was extracted from peripheral blood. CMT gene panel (50 genes + PMP22 duplication) testing and Whole Exome Sequencing (WES) were performed. Putative variant was confirmed through Sanger sequencing and segregation analysis was done. Western blot and Immunofluorescence analysis were performed.
Results: Seven patients (six males and one female) and their unaffected relatives from a large family were enrolled. The disease distribution was consistent with an autosomal dominant inheritance pattern. The mean age at diagnosis was 35.7 years, ranging from 12 to 65 years, and walking difficulty was the most common starting symptom. Neurological examination showed a distal muscle weakness and wasting, steppage gait, absent reflexes, mild sensory loss, and pes cavus. A high clinical variability was noted, but overall, symptoms were more pronounced in the upper limbs compared to the lower limbs. NCS were performed in four individuals and were consistent with an axonal-type neuropathy with marked motor involvement. CMT gene panel testing was first done and was negative. However, WES revealed a novel pathogenic missense variant at position c.1102G>T (Gly368Cys) in CADM3, segregating with the disease in the family. In addition, Western blot and Immunofluorescence analysis showed a significant decrease in the levels of CADM3-Gly368Cys mutant protein in the membrane and suggest that the new cysteine might interfere with the native disulfide bond important for the formation of the Ig-like loops.
Conclusions: We report a novel variant in CADM3, and provide further evidence of its implication in axonal-type CMT. A large collaborative study including patients from different genetic backgrounds may unveil several novel CMT genes or variants and inform the disease mechanism
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support: NIH Grant U01HG007044
Keywords: CMT, Next generation sequencing, CADM3, Novel variant, Mali
Poster No: 1297
Presenter: Abdoulaye Yalcouy©
Institution: University of Sciences Techniques and Technologies of Bamako
Introduction: Charcot-Marie-Tooth disease type 2FF caused by CADM3 variants was recently reported in three Caucasian families. We report here a novel variant in CADM3 in a Malian family with CMT
Methods: A careful clinical examination, and nerve conduction studies (NCS) were done. DNA was extracted from peripheral blood. CMT gene panel (50 genes + PMP22 duplication) testing and Whole Exome Sequencing (WES) were performed. Putative variant was confirmed through Sanger sequencing and segregation analysis was done. Western blot and Immunofluorescence analysis were performed.
Results: Seven patients (six males and one female) and their unaffected relatives from a large family were enrolled. The disease distribution was consistent with an autosomal dominant inheritance pattern. The mean age at diagnosis was 35.7 years, ranging from 12 to 65 years, and walking difficulty was the most common starting symptom. Neurological examination showed a distal muscle weakness and wasting, steppage gait, absent reflexes, mild sensory loss, and pes cavus. A high clinical variability was noted, but overall, symptoms were more pronounced in the upper limbs compared to the lower limbs. NCS were performed in four individuals and were consistent with an axonal-type neuropathy with marked motor involvement. CMT gene panel testing was first done and was negative. However, WES revealed a novel pathogenic missense variant at position c.1102G>T (Gly368Cys) in CADM3, segregating with the disease in the family. In addition, Western blot and Immunofluorescence analysis showed a significant decrease in the levels of CADM3-Gly368Cys mutant protein in the membrane and suggest that the new cysteine might interfere with the native disulfide bond important for the formation of the Ig-like loops.
Conclusions: We report a novel variant in CADM3, and provide further evidence of its implication in axonal-type CMT. A large collaborative study including patients from different genetic backgrounds may unveil several novel CMT genes or variants and inform the disease mechanism
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support: NIH Grant U01HG007044
Keywords: CMT, Next generation sequencing, CADM3, Novel variant, Mali
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