Tags

Type your tag names separated by a space and hit enter

Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene.
Arch Neurol. 2003 Apr; 60(4):598-604.AN

Abstract

BACKGROUND

The first locus for demyelinating autosomal recessive Charcot-Marie-Tooth (ARCMT) disease was identified in 8q13, where mutations in GDAP1 have been found. Mutations in the same gene have been detected in families with axonal ARCMT disease.

OBJECTIVE

To determine the clinical, electrophysiologic, and morphologic characteristics of a consanguineous Moroccan family with ARCMT disease associated with the S194X mutation in the GDAP1 gene.

METHODS

Four patients from a consanguineous Moroccan family were examined clinically and electrophysiologically. In one patient, a morphometric and ultrastructural study of a peroneal nerve biopsy sample was performed. Mutation in the coding region of the GDAP1 gene was identified by direct sequencing.

RESULTS

Neuropathy was evident early in childhood, walking was delayed in one patient, and onset of symptoms occurred before 18 months in the others. The phenotype was severe: foot deformities and disabilities involving the hands and feet developed toward the end of the first decade, followed by involvement of proximal muscles in the lower limbs, leading to loss of autonomy. Electrophysiologic findings were consistent with an axonal form of CMT disease: motor nerve conduction velocities, recordable in one patient only, were greater than 40 m/sec. Sensory nerve action potentials were either abolished or substantially reduced in amplitude. The morphologic data supported the diagnosis of axonal neuropathy, showing a marked reduction in myelinated fibers and signs of axonal regeneration, including frequent pseudo-onion bulb formations. The 4 patients in this family were homozygous for the S194X mutation in the GDAP1 gene.

CONCLUSION

Electrophysiologic and pathological findings support the hypothesis of an axonal disorder in this ARCMT family with the S194X mutation in the GDAP1 gene.

Authors+Show Affiliations

Service de Neurologie, Hôpital des Spécialités, Rabat, Morocco. birna@iam.net.maNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12707075

Citation

Birouk, Nazha, et al. "Phenotypical Features of a Moroccan Family With Autosomal Recessive Charcot-Marie-Tooth Disease Associated With the S194X Mutation in the GDAP1 Gene." Archives of Neurology, vol. 60, no. 4, 2003, pp. 598-604.
Birouk N, Azzedine H, Dubourg O, et al. Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene. Arch Neurol. 2003;60(4):598-604.
Birouk, N., Azzedine, H., Dubourg, O., Muriel, M. P., Benomar, A., Hamadouche, T., Maisonobe, T., Ouazzani, R., Brice, A., Yahyaoui, M., Chkili, T., & Le Guern, E. (2003). Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene. Archives of Neurology, 60(4), 598-604.
Birouk N, et al. Phenotypical Features of a Moroccan Family With Autosomal Recessive Charcot-Marie-Tooth Disease Associated With the S194X Mutation in the GDAP1 Gene. Arch Neurol. 2003;60(4):598-604. PubMed PMID: 12707075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene. AU - Birouk,Nazha, AU - Azzedine,Hamid, AU - Dubourg,Odile, AU - Muriel,Marie-Paule, AU - Benomar,Ali, AU - Hamadouche,Tarik, AU - Maisonobe,Thierry, AU - Ouazzani,Reda, AU - Brice,Alexis, AU - Yahyaoui,Mohamed, AU - Chkili,Taïb, AU - Le Guern,Eric, PY - 2003/4/23/pubmed PY - 2003/5/8/medline PY - 2003/4/23/entrez SP - 598 EP - 604 JF - Archives of neurology JO - Arch. Neurol. VL - 60 IS - 4 N2 - BACKGROUND: The first locus for demyelinating autosomal recessive Charcot-Marie-Tooth (ARCMT) disease was identified in 8q13, where mutations in GDAP1 have been found. Mutations in the same gene have been detected in families with axonal ARCMT disease. OBJECTIVE: To determine the clinical, electrophysiologic, and morphologic characteristics of a consanguineous Moroccan family with ARCMT disease associated with the S194X mutation in the GDAP1 gene. METHODS: Four patients from a consanguineous Moroccan family were examined clinically and electrophysiologically. In one patient, a morphometric and ultrastructural study of a peroneal nerve biopsy sample was performed. Mutation in the coding region of the GDAP1 gene was identified by direct sequencing. RESULTS: Neuropathy was evident early in childhood, walking was delayed in one patient, and onset of symptoms occurred before 18 months in the others. The phenotype was severe: foot deformities and disabilities involving the hands and feet developed toward the end of the first decade, followed by involvement of proximal muscles in the lower limbs, leading to loss of autonomy. Electrophysiologic findings were consistent with an axonal form of CMT disease: motor nerve conduction velocities, recordable in one patient only, were greater than 40 m/sec. Sensory nerve action potentials were either abolished or substantially reduced in amplitude. The morphologic data supported the diagnosis of axonal neuropathy, showing a marked reduction in myelinated fibers and signs of axonal regeneration, including frequent pseudo-onion bulb formations. The 4 patients in this family were homozygous for the S194X mutation in the GDAP1 gene. CONCLUSION: Electrophysiologic and pathological findings support the hypothesis of an axonal disorder in this ARCMT family with the S194X mutation in the GDAP1 gene. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/12707075/Phenotypical_features_of_a_Moroccan_family_with_autosomal_recessive_Charcot_Marie_Tooth_disease_associated_with_the_S194X_mutation_in_the_GDAP1_gene_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/vol/60/pg/598 DB - PRIME DP - Unbound Medicine ER -