RESUMEN
Congenital skin fragility is a heterogeneous disorder with epidermolysis bullosa and various skin infections as the leading causes. However, even rare diseases must be considered in the differential diagnosis of neonatal skin blistering, including some genetic syndromes with extracutaneous involvement. One such syndrome is ectodermal dysplasia due to deficiency of desmoplakin, a desmosomal protein essential for cellular cohesion in both epithelia and cardiac tissues. Desmoplakin is encoded by the DSP gene, which is localized on chromosome 6p24. Both dominant and recessive mutations in this gene have been reported to cause skin fragility and keratinization defects. We report a child born with a fragile epidermis, alopecia, thick nails, and focal hyperkeratoses on the digits and knees. She was found to have a deficiency of desmoplakin caused by compound heterozygous DSP mutations. She has gradually developed signs of a left ventricular cardiomyopathy.
Asunto(s)
Alopecia/genética , Desmoplaquinas/genética , Enfermedades Cutáneas Vesiculoampollosas/genética , Disfunción Ventricular Izquierda/genética , Preescolar , Femenino , Humanos , Mutación , SueciaAsunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Ictiosis Lamelar/diagnóstico , Mutación/genética , Diagnóstico Prenatal/métodos , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Ictiosis Lamelar/genética , Recién Nacido , Masculino , Datos de Secuencia Molecular , Embarazo , Diagnóstico Prenatal/normasRESUMEN
Autosomal recessive congenital ichthyosis (ARCI) is a group of keratinisation disorders that includes the ichthyosis prematurity syndrome (IPS). IPS is rare and almost exclusively present in a restricted region in the middle of Norway and Sweden, which indicates a founder effect for the disorder. We recently reported linkage of IPS to chromosome 9q34, and we present here the subsequent fine-mapping of this region with known and novel microsatellite markers as well as single nucleotide polymorphisms (SNPs). Allelic association, evaluated with Fisher's exact test and P (excess), was used to refine the IPS haplotype to approximately 1.6 Mb. On the basis of the average length of the haplotype in IPS patients, we calculated the age of a founder mutation to approximately 1,900 years. The IPS haplotype contains a core region of 76 kb consisting of four marker alleles shared by 97.7% of the chromosomes associated with IPS. This region spans four known genes, all of which are expressed in mature epidermal cells. We present the results from the analysis of these four genes and their corresponding transcripts in normal and patient-derived samples.