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Severe Psychomotor Retardation (severe + psychomotor_retardation)

Distribution by Scientific Domains

Life Sciences	75%

Selected Abstracts

Novel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2) mutations,

HUMAN MUTATION, Issue 1 2009
W. Edward Visser
Abstract Monocarboxylate transporter 8 (MCT8; approved symbol SLC16A2) facilitates cellular uptake and efflux of 3,3,,5-triiodothyronine (T3). Mutations in MCT8 are associated with severe psychomotor retardation, high serum T3 and low 3,3,,5,-triiodothyronine (rT3) levels. Here we report three novel MCT8 mutations. Two subjects with the F501del mutation have mild psychomotor retardation with slightly elevated T3 and normal rT3 levels. T3 uptake was mildly affected in F501del fibroblasts and strongly decreased in fibroblasts from other MCT8 patients, while T3 efflux was always strongly reduced. Moreover, type 3 deiodinase activity was highly elevated in F501del fibroblasts, whereas it was reduced in fibroblasts from other MCT8 patients, probably reflecting parallel variation in cellular T3 content. Additionally, T3-responsive genes were markedly upregulated by T3 treatment in F501del fibroblasts but not in fibroblasts with other MCT8 mutations. In conclusion, mutations in MCT8 result in a decreased T3 uptake in skin fibroblasts. The much milder clinical phenotype of patients with the F501del mutation may be correlated with the relatively small decrease in T3 uptake combined with an even greater decrease in T3 efflux. If fibroblasts are representative of central neurons, abnormal brain development associated with MCT8 mutations may be the consequence of either decreased or increased intracellular T3 concentrations. Hum Mutat 0,1-10, 2008. © 2008 Wiley-Liss, Inc. [source]

New mental retardation syndrome associated with ocular colobomas, cleft palate, and genital, skeletal, and craniofacial abnormalities

AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2002
M.M. Khalifa
Abstract We describe three Canadian brothers of Cree origin, with a previously undescribed pattern of malformation including distinctive craniofacial abnormalities with triangular facies, hypertelorism, low-set and posteriorly rotated ears, ocular colobomas, ptosis, brachycephaly with widely separated sutures, cleft soft palate, undescended testes, bifid scrotum and hypospadius, wide webbed neck, webbed fingers, pectus excavatum and hypersegmented sternum, and severe psychomotor retardation. The presence of normal brain imaging and physical growth distinguishes them from other syndromes with overlapping abnormalities. This is either an X-linked or autosomal recessive condition. © 2001 Wiley-Liss, Inc. [source]

Inhibition of defective adenylosuccinate lyase by HNE: A neurological disease that may be affected by oxidative stress

BIOFACTORS, Issue 1-4 2005
C. Crifò
Abstract Adenylosuccinate lyase is an enzyme of fumarase superfamily that participates in the purine biosynthetic pathway, catalysing the nonhydrolytic cleavage of succinyl groups from SAICA ribotide and adenylosuccinate. Enzyme defects are associated with a human inherited disease, which arises from single point mutations to the gene and results in mild to severe psychomotor retardation, epilepsy, muscle wasting, and autistic features. Adenylosuccinate lyase activity is lost to a different extent in the patients. Diminished levels of enzyme have been attributed to loss of catalytic activity, protein instability, or environmental factors. P100A/D422Y mutation represents a feasible model for studying the effect of cell milieu on the activity of the impaired enzyme. The defective enzyme is inhibited by micromolar concentrations of trans-4-hydroxy-2-nonenal (HNE), a major product of membrane peroxidation that has been found to accumulate in brain tissues of patients with neurodegenerative disorders. It is suggested that inactivation of defective adenylosuccinate lyase by HNE and other membrane peroxidation products may account, at least in part, for the impairment of neurological functions and recurrent worsening of the symptoms. [source]

West syndrome and mitochondrial diabetes: relationship or coincidence?

CLINICAL ENDOCRINOLOGY, Issue 1 2002
B. Bouhanick
Summary West syndrome occurs in infancy and in early childhood. It is characterized by intractable seizures occurring almost daily, severe psychomotor retardation, poor prognosis and EEG abnormalities, known as hypsarrhythmia. We report here the case of a 28-year-old patient, who was diagnosed with West syndrome when he was 8 months old and with diabetes mellitus when he was 25 years old. Sequencing analyses and restriction analyses were suggestive of mitochondrial diabetes. Four years after the diagnosis of diabetes, this patient's diabetes is still controlled by diet and biguanides. [source]