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Abstract
Discussion Forum (0)
Peculiar Phenotypical Findings in Intermediate-Charcot-Marie-Tooth Type C Associated With a Novel YARS1 Probably Pathogenic Variant
Poster No: 1226
Presenter: Gauthier Remiche
Institution: ULB Hôpital Erasme
Introduction: Monoallelic Tyrosyl-tRNA synthetase gene (YARS1) mutation may lead to autosomal dominant intermediate-Charcot–Marie–Tooth disease Type C (CMTDIC) (#MIM 608323). Intermediate CMT is characterized by motor median nerve conduction velocities between 25 and 45 m/s with several mode of inheritance. YARS1-related CMTDIC were very rarely worldwide described (<10 families). We aim to report a case of CMTDIC harboring a novel YARS1 probable pathogenic variant and to identify additional phenotypical findings to enlarge phenotype-genotype knowledge of that disease.
Methods: We describe a 48-year-old male patient presenting initially isolated fasciculations calves from the age of 20 years. At the age of 40, he developed difficulties to remain durably in standing position and reported exercise-related cramps, fatigue, hearing loss and fecal incontinence. The past medical and family histories were unremarkable. Clinical examination showed lower limbs distal amyotrophy, preserved reflexes and mild sensory impairment.
Results: Routine blood tests for excluding acquired peripheral neuropathy etiologies were normal. Conduction velocity study showed a dramatic decrease of distal compound muscle action potential and sensory nerve action potentials on the lower limbs. Motor and sensory nerve conduction velocities were preserved at lower and upper limbs. Needle electromyography (EMG) demonstrated giant motor unit action potentials in tibialis anterior muscles. Audiometry showed a loss of perception in high frequencies and external anal sphincter EMG revealed neurogenic signs. Clinical exome sequencing identified the heterozygous c.145C>T (p.His49Thr) variant. Its absence form control database GnomaAD, in silico analyses (prediction sites, Deogen score) and strong amino-acid conservation thorough species supported its pathogenic nature. The variant was not found in the father (mother being unavailable).
Conclusions: Describing a case of CMTDIC associated with a probable pathogenic variant of YARS1 and undescribed phenotypical findings being hearing loss, fecal incontinence and preserved nerve conduction velocities, we enlarge the phenotype-genotype comprehension of this very rare entity.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: CMTDIC, YARS1, incontinence, hearing loss
Poster No: 1226
Presenter: Gauthier Remiche
Institution: ULB Hôpital Erasme
Introduction: Monoallelic Tyrosyl-tRNA synthetase gene (YARS1) mutation may lead to autosomal dominant intermediate-Charcot–Marie–Tooth disease Type C (CMTDIC) (#MIM 608323). Intermediate CMT is characterized by motor median nerve conduction velocities between 25 and 45 m/s with several mode of inheritance. YARS1-related CMTDIC were very rarely worldwide described (<10 families). We aim to report a case of CMTDIC harboring a novel YARS1 probable pathogenic variant and to identify additional phenotypical findings to enlarge phenotype-genotype knowledge of that disease.
Methods: We describe a 48-year-old male patient presenting initially isolated fasciculations calves from the age of 20 years. At the age of 40, he developed difficulties to remain durably in standing position and reported exercise-related cramps, fatigue, hearing loss and fecal incontinence. The past medical and family histories were unremarkable. Clinical examination showed lower limbs distal amyotrophy, preserved reflexes and mild sensory impairment.
Results: Routine blood tests for excluding acquired peripheral neuropathy etiologies were normal. Conduction velocity study showed a dramatic decrease of distal compound muscle action potential and sensory nerve action potentials on the lower limbs. Motor and sensory nerve conduction velocities were preserved at lower and upper limbs. Needle electromyography (EMG) demonstrated giant motor unit action potentials in tibialis anterior muscles. Audiometry showed a loss of perception in high frequencies and external anal sphincter EMG revealed neurogenic signs. Clinical exome sequencing identified the heterozygous c.145C>T (p.His49Thr) variant. Its absence form control database GnomaAD, in silico analyses (prediction sites, Deogen score) and strong amino-acid conservation thorough species supported its pathogenic nature. The variant was not found in the father (mother being unavailable).
Conclusions: Describing a case of CMTDIC associated with a probable pathogenic variant of YARS1 and undescribed phenotypical findings being hearing loss, fecal incontinence and preserved nerve conduction velocities, we enlarge the phenotype-genotype comprehension of this very rare entity.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: CMTDIC, YARS1, incontinence, hearing loss
Peculiar Phenotypical Findings in Intermediate-Charcot-Marie-Tooth Type C Associated With a Novel YARS1 Probably Pathogenic Variant
Poster No: 1226
Presenter: Gauthier Remiche
Institution: ULB Hôpital Erasme
Introduction: Monoallelic Tyrosyl-tRNA synthetase gene (YARS1) mutation may lead to autosomal dominant intermediate-Charcot–Marie–Tooth disease Type C (CMTDIC) (#MIM 608323). Intermediate CMT is characterized by motor median nerve conduction velocities between 25 and 45 m/s with several mode of inheritance. YARS1-related CMTDIC were very rarely worldwide described (<10 families). We aim to report a case of CMTDIC harboring a novel YARS1 probable pathogenic variant and to identify additional phenotypical findings to enlarge phenotype-genotype knowledge of that disease.
Methods: We describe a 48-year-old male patient presenting initially isolated fasciculations calves from the age of 20 years. At the age of 40, he developed difficulties to remain durably in standing position and reported exercise-related cramps, fatigue, hearing loss and fecal incontinence. The past medical and family histories were unremarkable. Clinical examination showed lower limbs distal amyotrophy, preserved reflexes and mild sensory impairment.
Results: Routine blood tests for excluding acquired peripheral neuropathy etiologies were normal. Conduction velocity study showed a dramatic decrease of distal compound muscle action potential and sensory nerve action potentials on the lower limbs. Motor and sensory nerve conduction velocities were preserved at lower and upper limbs. Needle electromyography (EMG) demonstrated giant motor unit action potentials in tibialis anterior muscles. Audiometry showed a loss of perception in high frequencies and external anal sphincter EMG revealed neurogenic signs. Clinical exome sequencing identified the heterozygous c.145C>T (p.His49Thr) variant. Its absence form control database GnomaAD, in silico analyses (prediction sites, Deogen score) and strong amino-acid conservation thorough species supported its pathogenic nature. The variant was not found in the father (mother being unavailable).
Conclusions: Describing a case of CMTDIC associated with a probable pathogenic variant of YARS1 and undescribed phenotypical findings being hearing loss, fecal incontinence and preserved nerve conduction velocities, we enlarge the phenotype-genotype comprehension of this very rare entity.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: CMTDIC, YARS1, incontinence, hearing loss
Poster No: 1226
Presenter: Gauthier Remiche
Institution: ULB Hôpital Erasme
Introduction: Monoallelic Tyrosyl-tRNA synthetase gene (YARS1) mutation may lead to autosomal dominant intermediate-Charcot–Marie–Tooth disease Type C (CMTDIC) (#MIM 608323). Intermediate CMT is characterized by motor median nerve conduction velocities between 25 and 45 m/s with several mode of inheritance. YARS1-related CMTDIC were very rarely worldwide described (<10 families). We aim to report a case of CMTDIC harboring a novel YARS1 probable pathogenic variant and to identify additional phenotypical findings to enlarge phenotype-genotype knowledge of that disease.
Methods: We describe a 48-year-old male patient presenting initially isolated fasciculations calves from the age of 20 years. At the age of 40, he developed difficulties to remain durably in standing position and reported exercise-related cramps, fatigue, hearing loss and fecal incontinence. The past medical and family histories were unremarkable. Clinical examination showed lower limbs distal amyotrophy, preserved reflexes and mild sensory impairment.
Results: Routine blood tests for excluding acquired peripheral neuropathy etiologies were normal. Conduction velocity study showed a dramatic decrease of distal compound muscle action potential and sensory nerve action potentials on the lower limbs. Motor and sensory nerve conduction velocities were preserved at lower and upper limbs. Needle electromyography (EMG) demonstrated giant motor unit action potentials in tibialis anterior muscles. Audiometry showed a loss of perception in high frequencies and external anal sphincter EMG revealed neurogenic signs. Clinical exome sequencing identified the heterozygous c.145C>T (p.His49Thr) variant. Its absence form control database GnomaAD, in silico analyses (prediction sites, Deogen score) and strong amino-acid conservation thorough species supported its pathogenic nature. The variant was not found in the father (mother being unavailable).
Conclusions: Describing a case of CMTDIC associated with a probable pathogenic variant of YARS1 and undescribed phenotypical findings being hearing loss, fecal incontinence and preserved nerve conduction velocities, we enlarge the phenotype-genotype comprehension of this very rare entity.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: CMTDIC, YARS1, incontinence, hearing loss
Peculiar Phenotypical Findings in Intermediate-Charcot-Marie-Tooth Type C Associated With a Novel YARS1 Probably Pathogenic Variant
Prof. Dr. Gauthier Remiche
Abstract
Discussion Forum (0)
Peculiar Phenotypical Findings in Intermediate-Charcot-Marie-Tooth Type C Associated With a Novel YARS1 Probably Pathogenic Variant
Poster No: 1226
Presenter: Gauthier Remiche
Institution: ULB Hôpital Erasme
Introduction: Monoallelic Tyrosyl-tRNA synthetase gene (YARS1) mutation may lead to autosomal dominant intermediate-Charcot–Marie–Tooth disease Type C (CMTDIC) (#MIM 608323). Intermediate CMT is characterized by motor median nerve conduction velocities between 25 and 45 m/s with several mode of inheritance. YARS1-related CMTDIC were very rarely worldwide described (<10 families). We aim to report a case of CMTDIC harboring a novel YARS1 probable pathogenic variant and to identify additional phenotypical findings to enlarge phenotype-genotype knowledge of that disease.
Methods: We describe a 48-year-old male patient presenting initially isolated fasciculations calves from the age of 20 years. At the age of 40, he developed difficulties to remain durably in standing position and reported exercise-related cramps, fatigue, hearing loss and fecal incontinence. The past medical and family histories were unremarkable. Clinical examination showed lower limbs distal amyotrophy, preserved reflexes and mild sensory impairment.
Results: Routine blood tests for excluding acquired peripheral neuropathy etiologies were normal. Conduction velocity study showed a dramatic decrease of distal compound muscle action potential and sensory nerve action potentials on the lower limbs. Motor and sensory nerve conduction velocities were preserved at lower and upper limbs. Needle electromyography (EMG) demonstrated giant motor unit action potentials in tibialis anterior muscles. Audiometry showed a loss of perception in high frequencies and external anal sphincter EMG revealed neurogenic signs. Clinical exome sequencing identified the heterozygous c.145C>T (p.His49Thr) variant. Its absence form control database GnomaAD, in silico analyses (prediction sites, Deogen score) and strong amino-acid conservation thorough species supported its pathogenic nature. The variant was not found in the father (mother being unavailable).
Conclusions: Describing a case of CMTDIC associated with a probable pathogenic variant of YARS1 and undescribed phenotypical findings being hearing loss, fecal incontinence and preserved nerve conduction velocities, we enlarge the phenotype-genotype comprehension of this very rare entity.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: CMTDIC, YARS1, incontinence, hearing loss
Poster No: 1226
Presenter: Gauthier Remiche
Institution: ULB Hôpital Erasme
Introduction: Monoallelic Tyrosyl-tRNA synthetase gene (YARS1) mutation may lead to autosomal dominant intermediate-Charcot–Marie–Tooth disease Type C (CMTDIC) (#MIM 608323). Intermediate CMT is characterized by motor median nerve conduction velocities between 25 and 45 m/s with several mode of inheritance. YARS1-related CMTDIC were very rarely worldwide described (<10 families). We aim to report a case of CMTDIC harboring a novel YARS1 probable pathogenic variant and to identify additional phenotypical findings to enlarge phenotype-genotype knowledge of that disease.
Methods: We describe a 48-year-old male patient presenting initially isolated fasciculations calves from the age of 20 years. At the age of 40, he developed difficulties to remain durably in standing position and reported exercise-related cramps, fatigue, hearing loss and fecal incontinence. The past medical and family histories were unremarkable. Clinical examination showed lower limbs distal amyotrophy, preserved reflexes and mild sensory impairment.
Results: Routine blood tests for excluding acquired peripheral neuropathy etiologies were normal. Conduction velocity study showed a dramatic decrease of distal compound muscle action potential and sensory nerve action potentials on the lower limbs. Motor and sensory nerve conduction velocities were preserved at lower and upper limbs. Needle electromyography (EMG) demonstrated giant motor unit action potentials in tibialis anterior muscles. Audiometry showed a loss of perception in high frequencies and external anal sphincter EMG revealed neurogenic signs. Clinical exome sequencing identified the heterozygous c.145C>T (p.His49Thr) variant. Its absence form control database GnomaAD, in silico analyses (prediction sites, Deogen score) and strong amino-acid conservation thorough species supported its pathogenic nature. The variant was not found in the father (mother being unavailable).
Conclusions: Describing a case of CMTDIC associated with a probable pathogenic variant of YARS1 and undescribed phenotypical findings being hearing loss, fecal incontinence and preserved nerve conduction velocities, we enlarge the phenotype-genotype comprehension of this very rare entity.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: CMTDIC, YARS1, incontinence, hearing loss
Peculiar Phenotypical Findings in Intermediate-Charcot-Marie-Tooth Type C Associated With a Novel YARS1 Probably Pathogenic Variant
Poster No: 1226
Presenter: Gauthier Remiche
Institution: ULB Hôpital Erasme
Introduction: Monoallelic Tyrosyl-tRNA synthetase gene (YARS1) mutation may lead to autosomal dominant intermediate-Charcot–Marie–Tooth disease Type C (CMTDIC) (#MIM 608323). Intermediate CMT is characterized by motor median nerve conduction velocities between 25 and 45 m/s with several mode of inheritance. YARS1-related CMTDIC were very rarely worldwide described (<10 families). We aim to report a case of CMTDIC harboring a novel YARS1 probable pathogenic variant and to identify additional phenotypical findings to enlarge phenotype-genotype knowledge of that disease.
Methods: We describe a 48-year-old male patient presenting initially isolated fasciculations calves from the age of 20 years. At the age of 40, he developed difficulties to remain durably in standing position and reported exercise-related cramps, fatigue, hearing loss and fecal incontinence. The past medical and family histories were unremarkable. Clinical examination showed lower limbs distal amyotrophy, preserved reflexes and mild sensory impairment.
Results: Routine blood tests for excluding acquired peripheral neuropathy etiologies were normal. Conduction velocity study showed a dramatic decrease of distal compound muscle action potential and sensory nerve action potentials on the lower limbs. Motor and sensory nerve conduction velocities were preserved at lower and upper limbs. Needle electromyography (EMG) demonstrated giant motor unit action potentials in tibialis anterior muscles. Audiometry showed a loss of perception in high frequencies and external anal sphincter EMG revealed neurogenic signs. Clinical exome sequencing identified the heterozygous c.145C>T (p.His49Thr) variant. Its absence form control database GnomaAD, in silico analyses (prediction sites, Deogen score) and strong amino-acid conservation thorough species supported its pathogenic nature. The variant was not found in the father (mother being unavailable).
Conclusions: Describing a case of CMTDIC associated with a probable pathogenic variant of YARS1 and undescribed phenotypical findings being hearing loss, fecal incontinence and preserved nerve conduction velocities, we enlarge the phenotype-genotype comprehension of this very rare entity.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: CMTDIC, YARS1, incontinence, hearing loss
Poster No: 1226
Presenter: Gauthier Remiche
Institution: ULB Hôpital Erasme
Introduction: Monoallelic Tyrosyl-tRNA synthetase gene (YARS1) mutation may lead to autosomal dominant intermediate-Charcot–Marie–Tooth disease Type C (CMTDIC) (#MIM 608323). Intermediate CMT is characterized by motor median nerve conduction velocities between 25 and 45 m/s with several mode of inheritance. YARS1-related CMTDIC were very rarely worldwide described (<10 families). We aim to report a case of CMTDIC harboring a novel YARS1 probable pathogenic variant and to identify additional phenotypical findings to enlarge phenotype-genotype knowledge of that disease.
Methods: We describe a 48-year-old male patient presenting initially isolated fasciculations calves from the age of 20 years. At the age of 40, he developed difficulties to remain durably in standing position and reported exercise-related cramps, fatigue, hearing loss and fecal incontinence. The past medical and family histories were unremarkable. Clinical examination showed lower limbs distal amyotrophy, preserved reflexes and mild sensory impairment.
Results: Routine blood tests for excluding acquired peripheral neuropathy etiologies were normal. Conduction velocity study showed a dramatic decrease of distal compound muscle action potential and sensory nerve action potentials on the lower limbs. Motor and sensory nerve conduction velocities were preserved at lower and upper limbs. Needle electromyography (EMG) demonstrated giant motor unit action potentials in tibialis anterior muscles. Audiometry showed a loss of perception in high frequencies and external anal sphincter EMG revealed neurogenic signs. Clinical exome sequencing identified the heterozygous c.145C>T (p.His49Thr) variant. Its absence form control database GnomaAD, in silico analyses (prediction sites, Deogen score) and strong amino-acid conservation thorough species supported its pathogenic nature. The variant was not found in the father (mother being unavailable).
Conclusions: Describing a case of CMTDIC associated with a probable pathogenic variant of YARS1 and undescribed phenotypical findings being hearing loss, fecal incontinence and preserved nerve conduction velocities, we enlarge the phenotype-genotype comprehension of this very rare entity.
References: No
References 1:
References 2:
References 3:
References 4:
Grant Support:
Keywords: CMTDIC, YARS1, incontinence, hearing loss
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