RESUMO
Mutations in the ganglioside-induced differentiation associated-protein 1 (GDAP1) gene have been associated with both autosomal recessive (AR) and dominant (AD) Charcot-Marie-Tooth (CMT) axonal neuropathy. The relative frequency of heterozygous, dominant mutations in Italian CMT is unknown. We investigated the frequency of dominant mutations in GDAP1 in a cohort of 109 axonal Italian patients by sequencing genomic DNA and search for copy number variations. We also explored correlations with clinical features. All cases had already been tested for variants in common axonal AD genes. Eight patients (7.3%) harbored five already reported heterozygous mutations in GDAP1 (p.Arg120Gly, p.Arg120Trp, p.His123Arg, p.Gln218Glu, p.Arg226Ser). Mutations had different penetrances in the families; the onset of symptoms is in the first decade and progression is slower than usually seen in GDAP1-related AR-CMT. We show that the relative frequency of mutations in GDAP was slightly higher than those observed in MFN2 and MPZ (7.3% vs 6.3% and 5.0%). The relatively milder clinical features and the quite indolent course observed are relevant for prognostic assessment. On the basis of our experience and the data reported here, we suggest GDAP1 as the first gene that should be analysed in Italian patients affected by CMT2.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/fisiopatologia , Mutação/genética , Proteínas do Tecido Nervoso/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vias Autônomas/patologia , Vias Autônomas/fisiopatologia , Doença de Charcot-Marie-Tooth/patologia , Criança , Análise Mutacional de DNA , Saúde da Família , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Condução Nervosa/genética , Fenótipo , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease type 1X (CMT1X) is an X-linked dominant hereditary motor-sensory peripheral neuropathy, which results from mutations in the Gap Junction B1 (GJB1) gene. In a few cases, gene deletions have been linked to the disease, but their relative contribution in the pathogenesis of CMT1X has not been assessed yet. Herein a retrospective study to establish the incidence of gene deletions is described. METHODS: Copy number variation analysis was performed by multiplex ligation-dependent probe amplification, whilst the breakpoints were defined by Sanger sequencing. RESULTS: A novel GJB1 deletion was identified in a family presenting with a classical CMT1X phenotype. The rearrangement includes the coding and the regulatory regions of GJB1. CONCLUSIONS: GJB1 deletions appear to be a rare but not insignificant cause of CMT1X and are associated with a typical disease phenotype. Accordingly, patients negative for point mutations whose pedigree and clinical records strongly suggest the possibility of CMT1X should be tested for GJB1 copy number variations.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Conexinas/genética , Variações do Número de Cópias de DNA , Deleção de Genes , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Proteína beta-1 de Junções ComunicantesRESUMO
Midline cervical cysts are one of the most common embryological anomalies of the neck. They are due to the failure of a complete obliteration of the thyroglossal duct. This endodermal structure arises from the floor of the mouth and proceeds caudally in the midline of the neck until it reaches its final position around the trachea. Finally, the inferior portion of the thyroglossal duct develops into the median lobe of the thyroid gland whereas its cranial portion disappears. In the present paper, the clinical feature and the surgical treatment of a case is described.
