A Novel Mutation in FGD4/FRABIN Causes Charcot Marie Tooth Disease Type 4H in Patients from a Consanguineous Tunisian Family

作者：Boubaker Chokri; Hsairi Guidara Ines; Castro Christel; Ayadi Ines; Boyer Amandine; Kerkeni Emna; Courageot Joel; Abid Imen; Bernard Rafaelle; Bonello Palot Nathalie; Kamoun Fatma; Ben Cheikh Hassen; Levy Nicolas; Triki Chahnez; Delague Valerie^*

来源：Annals of Human Genetics, 2013, 77(4): 336-343.

DOI：10.1111/ahg.12017

• Charcot-Marie-Tooth disease
• FRABIN
• disease gene
• homozygous mutation
• neuropathy
• peripheral nerve

Charcot-Marie-Tooth (CMT) disease constitutes a clinically and genetically heterogeneous group of hereditary neuropathies characterized by progressive muscular and sensory loss in the distal extremities with chronic distal weakness, deformation of the feet, and loss of deep tendon reflexes. CMT4H is an autosomal recessive demyelinating subtype of CMT, due to mutations in FGD4/FRABIN, for which nine mutations are described to date. In this study, we describe three patients from a consanguineous Tunisian family, presenting with severe, early onset, slowly progressive, autosomal recessive demyelinating CMT, complicated by mild to severe kyphoscoliosis, consistent with CMT4H. In these patients, we report the identification of a novel homozygous frameshift mutation in FGD4: c.514_515insG; p.Ala172Glyfs*27. Our study reports the first mutation identified in FGD4 in Tunisian patients affected with CMT. It further confirms the important clinical heterogeneity observed in patients with mutations in FGD4 and the lack of phenotype/genotype correlations in CMT4H. Our results suggest that FGD4 should be screened in other early-onset CMT subtypes, regardless of the severity of the phenotype, and particularly in patients of consanguineous descent. In Tunisians, as in other populations with high consanguinity rates, screening of genes responsible for rare autosomal recessive CMT subtypes should be prioritized.

• 出版日期2013-7