A novel SLC6A8 mutation associated with motor dysfunction in a child exhibiting creatine transporter deficiency.

Creatine transporter (CT) deficiency is an X-linked disorder caused by mutations in the SLC6A8 gene. We describe a clinical, biochemical and molecular examination of a child with X-linked cerebral creatine deficiency. Increased urinary creatine/creatinine ratio, abnormal brain proton magnetic resonance spectroscopy and reduced creatine transport confirmed the clinical diagnosis.

Outcome of ABCA4 disease-associated alleles in autosomal recessive retinal dystrophies: retrospective analysis in 420 Spanish families.

Objective: To provide a comprehensive overview of all detected mutations in the ABCA4 gene in Spanish families with autosomal recessive retinal disorders, including Stargardt's disease (arSTGD), cone-rod dystrophy (arCRD), and retinitis pigmentosa (arRP), and to assess genotype-phenotype correlation and disease progression in 10 years by considering the type of variants and age at onset.

Design: Case series.

Participants: A total of 420 unrelated Spanish families: 259 arSTGD, 86 arCRD, and 75 arRP.

Further associations between mutations and polymorphisms in the ABCA4 gene: clinical implication of allelic variants and their role as protector/risk factors.

Purpose: Mutations in ABCA4 have been associated with autosomal recessive Stargardt disease, autosomal recessive cone-rod dystrophy, and autosomal recessive retinitis pigmentosa. The purpose of this study was to determine (1) associations among mutations and polymorphisms and (2) the role of the polymorphisms as protector/risk factors.

Methods: A case-control study was designed in which 128 Spanish patients and 84 control individuals were analyzed.

Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray.

Purpose: Retinitis pigmentosa (RP) is a genetically heterogeneous disorder characterized by progressive loss of vision. The aim of this study was to identify the causative mutations in 272 Spanish families using a genotyping microarray.

Methods: 272 unrelated Spanish families, 107 with autosomal recessive RP (arRP) and 165 with sporadic RP (sRP), were studied using the APEX genotyping microarray.

Comparison of high-resolution melting analysis with denaturing high-performance liquid chromatography for mutation scanning in the ABCA4 gene.

Purpose: Mutations in the ABCA4 gene have been associated with autosomal recessive Stargardt disease (STGD), a few cases of autosomal recessive cone-rod dystrophy (arCRD), and autosomal recessive retinitis pigmentosa (arRP). The purpose of this study was to compare high-resolution melting (HRM) analysis with denaturing high-performance liquid chromatography (dHPLC), to evaluate the efficiency of the different screening methodologies.

Methods: Thirty-eight STGD, 15 arCRD, and 5 arRP unrelated Spanish patients who had been analyzed with the ABCR microarray were evaluated.

ABCA4 mutations in Portuguese Stargardt patients: identification of new mutations and their phenotypic analysis.

Purpose: To resolve the spectrum of causative retina-specific ATP-binding cassette transporter gene (ABCA4) gene mutations in Portuguese Stargardt (STGD) patients and compare allele frequencies obtained in this cohort with those of previous population surveys.

Methods: Using a microarray technique (ABCR400 gene chip), we screened all previously reported ABCA4 gene mutations in the genomic DNA of 27 patients from 21 unrelated Stargardt families whose phenotypes had been clinically evaluated using psychophysics and electrophysiological measurements. Furthermore, we performed denaturing high performance liquid chromatography whenever one or both mutant alleles failed to be detected using the ABCR gene chip.

Correlation of genetic and clinical findings in Spanish patients with X-linked juvenile retinoschisis.

Purpose: X-linked juvenile retinoschisis (XLRS) is one of the most common causes of juvenile macular degeneration in males, characterized by microcystic changes, splitting within the inner retinal layer (schisis), and the presence of vitreous veils. This study was conducted to describe and further correlate specific genetic variation in Spanish patients with XLRS with clinical characteristics and additional ophthalmic complications.

Methods: The study was performed in 34 Spanish families with XLRS, comprising 51 affected males.

CERKL mutations and associated phenotypes in seven Spanish families with autosomal recessive retinitis pigmentosa.

Purpose: Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinopathies. Up to now, 39 genes and loci have been implicated in nonsyndromic RP, yet the genetic bases of >50% of the cases, particularly of the recessive forms, remain unknown. A novel gene (CERKL) has been described as associated with RP26.

Molecular analysis of ABCA4 and CRB1 genes in a Spanish family segregating both Stargardt disease and autosomal recessive retinitis pigmentosa.

Purpose: Stargardt disease (STGD), characterized by central visual impairment, is the most common juvenile macular dystrophy. All recessively inherited cases are thought to be due to mutations in the ABCA4 gene. Early-onset autosomal recessive retinitis pigmentosa (arRP) is a severe retinal degeneration that presents before the patient is ten years old.

Frequency of CEP290 c.2991_1655A>G mutation in 175 Spanish families affected with Leber congenital amaurosis and early-onset retinitis pigmentosa.

Purpose: Leber congenital amaurosis (LCA) is the most severe inherited retinopathy with the earliest age of onset. To date, eleven genes have been reported to cause the non-syndromic LCA phenotype. The CEP290 gene has been shown to account for Joubert and Senior-Loken syndromes and to represent a frequent cause of non-syndromic LCA.

Mutation screening of 299 Spanish families with retinal dystrophies by Leber congenital amaurosis genotyping microarray.

Purpose: Leber Congenital Amaurosis (LCA) is one of the most severe inherited retinal dystrophies with the earliest age of onset. This study was a mutational analysis of eight genes (AIPL1, CRB1, CRX, GUCY2D, RPE65, RPGRIP1, MERTK, and LRAT) in 299 unrelated Spanish families, containing 42 patients with initial diagnosis of LCA: 107 with early-onset autosomal recessive retinitis pigmentosa (ARRP; onset <10 years of age) and 150 with non-early-onset ARRP (onset, >10 years of age).

Methods: Samples were studied by using a genotyping microarray (Asper Biotech, Ltd.