Clinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease.

INTRODUCTION: Charcot-Marie-Tooth (CMT) disease is classified considering the neurophysiological and histological findings, the inheritance pattern and the underlying genetic defect. In recent years, with the advent of next generation sequencing, genetic complexity has increased exponentially, expanding the knowledge about disease pathways, and having an impact in clinical management. The aim of this guide is to offer recommendations for the diagnosis, prognosis, monitoring and treatment of this disease in Spain. MATERIAL AND METHODS: This consensus guideline has been developed by a multidisciplinary panel encompassing a broad group of professionals including neurologists, neuropediatricians, geneticists, rehabilitators, and orthopaedic surgeons. RECOMMENDATIONS: The diagnosis is based in the clinical characterization, usually presenting with a common phenotype. It should be followed by an appropriate neurophysiological study that allows for a correct classification, specific recommendations are established for the parameters that should be included. Genetic diagnosis must be approached in sequentially, once the PMP22 duplication has been ruled out if appropriate, a next generation sequencing should be considered taking into account the limitations of the available techniques. To date, there is no pharmacological treatment that modifies the course of the disease, but symptomatic management is important, as are the rehabilitation and orthopaedic considerations. The latter should be initiated early to identify and improve the patient's functional impairments, including individualised exercise guidelines, orthotic adaptation, and assessment of conservative surgeries such as tendon transpositions. The follow-up of patients with CMT is exclusively clinical, ancillary testing are not necessary in routine clinical practice.

El diagnóstico clínico-molecular en la hipoplasia de cartílago-pelo: dos nuevos casos / Clinical and molecular diagnostics of a cartilage-hair hypoplasia: two new cases

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Prenatal diagnosis of skeletal dysplasia due to FGFR3 gene mutations: a 9-year experience : prenatal diagnosis in FGFR3 gene.

PURPOSE: Prenatal diagnosis with ultrasound findings compatible with skeletal dysplasia due to FGFR3 mutations over a 9 year period in pregnancies and abortuses. METHODS: 54 samples were studied. Aneuploidy studies were carried out on all samples. By sequencing analysis, we determined mutations for achondroplasia (ACH), hypochondroplasia (HCH), and type I and type II tanathophoric dysplasia (TD). RESULTS: 2 chorionic villi samples had a G380R mutation due to a mother with ACH; 4 amniotic fluid samples with TDs in which the foetuses had micromelia plus hypoplastic thoraces; 5 samples from abortuses with TDs. Neither ACH nor HCH occurred in sporadic cases. CONCLUSIONS: Molecular studies in ongoing pregnancies are indicated in cases with an affected parent, a family history with positive molecular studies (maternal anxiety), and when the US finding demonstrates micromelia with a hypoplastic thorax. A protocol for tissues of abortuses should include an X-ray, pathologic anatomy, and genetic studies.

Two non-contiguous duplications in the DMD gene in a Spanish family.

DMD and BMD are X-linked myopathy diseases in most cases caused by intragenic deletions, but duplications also appear in a significant number of cases. We present a complex duplication pattern detected by MLPA, a recently formulated method applied here to amplify the 79 exons of the DMD gene. We found a double-duplication in two DMD-affected brothers and in their carrier mother, which consist of two non-contiguous duplications encompassing exons 2 to 7 and exons 50 to 55. Different models are presented to explain formation of this genetic variant.

Evaluación de un método de ultracentrifugación en gradiente de densidad para la cuantificación de colesterol y triglicéridos en las lipoproteínas HDL, LDL y VLDL / Quantification of cholesterol and triglycerides in HDL, LDL and VLDL lipoproteins using a density gradient ultracentrifugation method

OBJETIVO: Adaptación de un método de ultracentrifugaciónen gradiente de densidad isopícnico para la separación analíticade de las tres principales lipoproteínas de interés clínico.MATERIAL Y MÉTODOS: Se procesaron 337 muestras, enuna ultracentrífuga Beckman L-80 con un rotor Vti 65.2, a416.000g durante 55 minutos a 10ºC. Los tubos de ultracentrifugación(5.1ml), se prepararon introduciendo 1ml de suero,previamente ajustado a una densidad de 1.210 Kg/l con BrK, yse rellenaron con una solución de BrK de densidad 1.006Kg/l.RESULTADOS: La fracción de HDL se recogió en los primeros1.7 ml, la de LDL en los siguientes 2.5 ml y la de VLDL enlos últimos 0.9 ml del volumen total. Los CV intraensayo oscilaronentre 0.71 y 11.41% y los CV interensayo entre 1.53 y11.11%. Los coeficientes de correlación fluctuaron entre0.707 y 0.982.CONCLUSIONES: El método de ultracentrifugación en gradientede densidad isopícnico propuesto es sencillo y fiable,permite separar las tres principales lipoproteínas (HDL, LDL yVLDL) y cuantificar independientemente en cada una de ellascolesterol y triglicéridos, en un único paso, en sólo 55 minutosy con un volumen de muestra mínimo (1ml). Lo consideramosun método útil cuando los métodos directos no son suficientementeexactos y cuando se necesita cuantificar los triglicéridos

OBJECTIVE, Adaptation of the ultracentrifugation metodologyin isopicnic density gradient with a vertical rotor to get theanalytical isolation of the three main lipoproteins for clinicaluse.DESIGN AND METHOD, Blood samples were obtained from337 subjects admitted at our Hospital. Sera were adjusted to1.210 kg/L density with KBr and filled with a 1.006 kg/L densityKBr solution. Tubes were processed in L-80 Beckman ultracentrifugeusing a VTi 65.2 rotor at 416 000g for 55 min at10ºC. RESULTS, HDL fraction was collected from initial until upto 1.7 mL, LDL fraction in the following 2.5 mL and VLDL fractionin the last 0.9 mL.The intraassay CVw were 0.71-11.41% and the interassayCVb, 1.53-11.11%. The correlation coefficients fluctuatedbetween 0.707-0.982.CONCLUSIONS, We propose a modified isopicnic densitygradient ultracentrifugation method that is both an easy and reliable technique, which separates and quantifies cholesteroland triglycerides in the three main lipoproteins (HDL, LDL andVLDL) independently, in one step, in a short time (55 min) andwith a minimal sample volume (1 mL).Therefore it is an useful method when direct methods are notaccurate enough and when quantification of triglycerides is needed