Premium
A Novel Mutation in FGD4/FRABIN Causes Charcot Marie Tooth Disease Type 4H in Patients from a Consanguineous Tunisian Family
Author(s) -
Boubaker Chokri,
HsairiGuidara Inès,
Castro Christel,
Ayadi Ines,
Boyer Amandine,
Kerkeni Emna,
Courageot Joël,
Abid Imen,
Bernard Rafaëlle,
BonelloPalot Nathalie,
Kamoun Fatma,
Cheikh Hassen Ben,
Lévy Nicolas,
Triki Chahnez,
Delague Valérie
Publication year - 2013
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12017
Subject(s) - consanguinity , genetic heterogeneity , frameshift mutation , genetics , medicine , hereditary motor and sensory neuropathy , founder effect , consanguineous marriage , mutation , phenotype , disease , tooth disease , age of onset , chinese family , biology , genotype , gene , pathology , haplotype
Summary 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.