RESUMO
Familial hyperCKemia is a rare condition, and a combination with Duchenne muscular dystrophy (DMD) is extremely rare. A boy showed muscle weakness from the age of 10 months and presented typical signs of DMD at the age of 18 months. The diagnosis was supported by markedly elevated serum creatine kinase (CK) value as well as by neurophysiological and muscle biopsy findings at the age of 23 months. The diagnosis was confirmed by identification of a stop codon in exon 43 (p.2095Arg>X) of the dystrophin gene. Interestingly, the father and his near relatives had increased serum CK values without any clinical symptoms or signs, nor a defect in caveolin-3 gene. We suggest that the occurrence of familial hyperCKemia may have triggered the early onset of symptoms in our patient.
Assuntos
Creatina Quinase/sangue , Doenças Metabólicas/enzimologia , Distrofia Muscular de Duchenne/enzimologia , Regulação para Cima/genética , Biópsia , Criança , Pré-Escolar , Códon de Terminação/genética , Análise Mutacional de DNA , Progressão da Doença , Distrofina/genética , Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Humanos , Lactente , Masculino , Doenças Metabólicas/genética , Doenças Metabólicas/fisiopatologia , Debilidade Muscular/enzimologia , Debilidade Muscular/genética , Debilidade Muscular/fisiopatologia , Músculo Esquelético/enzimologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/fisiopatologia , Mutação/genéticaRESUMO
X-linked mental retardation (XLMR) affects one in 600 males and is highly heterogeneous. We describe here a 29-year-old woman with severe nonsyndromic mental retardation and a balanced reciprocal translocation between chromosomes X and 15 [46,XX,t(X;15)(q13.3;cen)]. Methylation studies showed a 100% skewed X-inactivation in patient-derived lymphocytes indicating that the normal chromosome X is retained inactive. Physical mapping of the breakpoints localised the Xq13.3 breakpoint to within 3.9 kb of the first exon of the ZDHHC15 gene encoding a zinc-finger and a DHHC domain containing product. Expression analysis revealed that different transcript variants of the gene are expressed in brain. ZDHHC15-specific RT-PCR analysis on lymphocytes from the patient revealed an absence of ZDHHC15 transcript variants, detected in control samples. We suggest that the absence of the ZDHHC15 transcripts in this patient contributes to her phenotype, and that the gene is a strong candidate for nonsyndromic XLMR.
Assuntos
Cromossomos Humanos Par 15 , Proteínas de Ligação a DNA/metabolismo , Deficiência Intelectual Ligada ao Cromossomo X/genética , Translocação Genética , Adulto , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Metilação de DNA , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Deficiência Intelectual Ligada ao Cromossomo X/metabolismo , Dados de Sequência Molecular , Mutação , Inativação do Cromossomo XRESUMO
Autosomal dominant leukodystrophy (ADLD) with autonomic symptoms is a slowly progressive leukodystrophy with an onset in the 4th to 6th decade of life. Early symptoms are derived from the autonomic nervous system with bladder dysfunction in the majority of patients. The disease progresses slowly with loss of fine motor skills, ataxia, and affected individuals may survive for two decades after onset of symptoms. The molecular basis behind ADLD remains unknown but the causative locus was previously mapped to a 4 cM region on chromosome 5. We have recently identified a large family of Swedish origin with this type of ADLD. Linkage analysis on samples from family members confirmed linkage to 5q23 and supports genetic homogeneity for the disease. We fine mapped and localized the ADLD gene to a 0.96 cM region between D5S1495 and CTT/CCT15. A maximum parametric multipoint location score of 9.45 was obtained for a position at the marker CTT55. From our results we conclude that the ADLD gene locus is restricted to a 1.47 Mbp interval containing 13 known or putative genes.