Females heterozygous for creatine transporter deficiency
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چکیده
The creatine transporter deficiency is an X-linked cause of intellectual disability. We investigated the clinical features and pattern of X-inactivation in a Dutch cohort of eight female heterozygotes. We show that symptoms of the creatine transporter deficiency (intellectual disability, learning difficulties, constipation) can be present in female heterozygotes. We further show that the diagnosis in females is not straightforward: (1) The creatine/creatinine ratio in urine was elevated only in three out of eight females. (2) Although as a group the females had a significantly decreased cerebral creatine concentration, individual females had creatine concentrations overlapping with normal controls. (3) Skewed X-inactivation was found in the cultured fibroblasts, in favor of either the mutated or the wild-type allele, leading to either deficient or normal results in the creatine uptake studies in fibroblasts. Thus, screening by these tests is unreliable for the diagnosis. In addition, we found no consistent skewing of the X-inactivation in peripheral tissues indicating that there is no selection against the creatine transporter deficiency. We conclude that testing for creatine transporter deficiency should be considered in females with (mild) intellectual disability. Screening by DNA analysis of the SLC6A8 gene is recommended. Clinical features and X-inactivation in female heterozygotes 91 3.
منابع مشابه
Clinical features and X-inactivation in females heterozygous for creatine transporter defect.
The creatine transporter defect is an X-linked cause of mental retardation. We investigated the clinical features and pattern of X-inactivation in a Dutch cohort of eight female heterozygotes. We show that symptoms of the creatine transporter defect (mental retardation, learning difficulties, and constipation) can be present in female heterozygotes. We further show that the diagnosis in females...
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