Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Desbuquois dysplasia is a rare chondrodysplasia characterized by short stature, joint laxity, and specific radiographic findings. We report the natural history of four patients (three boys and one girl) with Desbuquois dysplasia ages 16-22 years. The mean height in adulthood was 114 cm (-8.5 SD) with progressive deceleration of the growth curve from birth (-4 SD) to adulthood. Obesity was noted consistently and facial abnormalities were still present but less obvious than in childhood. Three of four patients had mental retardation of varying degree. Hyperlaxity was persistent but limited motion of various joints was also noted. Orthopedic complications included coxa vara or valga (3/4), scoliosis (3/4), marked lordosis (3/4), and ambulatory difficulties (3/4). Surgical treatment was necessary for all four patients, involving large joints, spine and hands. Other complications included acute open-angle glaucoma secondary to a congenital malformation of the angle in one case. In addition to consistent radiological findings, elevated greater trochanter, generalized osteoporosis especially of the spine, scoliosis and/or lordosis, wide metaphyses, flat epiphyses, and coxa vara or valga were part of the natural history of the disorder. Our study emphasizes the care of older patients with Desbuquois dysplasia.
 ...
PMID:Long-term outcome in Desbuquois dysplasia: a follow-up in four adult patients. 1467 87

A 23-year-old female with Costello syndrome is presented. She had mental retardation, macrocephalia, "coarse" facial features, deep palmar and plantar creases, hyperkeratosis in palms and soles, hyperpigmentation, curly hair, and cutis laxa, which are among the diagnostic features of the syndrome, and a history of hyperprolactinemia since the age of 16. Her present complaint was weakness and widespread bone-pain. In routine biochemistry, she had an elevated calcium level of 11.1 (8.6-10.2) mg/dl and her DEXA evaluation was consistent with osteoporosis (vertebra and femur T score <-2.5). High PTH levels, 103 (8-78) pg/ml, suggested presence of a parathyroid adenoma. Tc-MIBI scintigraphy revealed two focuses of pathological uptake, one located inferior to left lobe of thyroid and the other in the superior left lobe of thyroid gland. After parathyroid adenomectomy, her serum calcium and PTH levels returned to normal values. This is the first case of parathyroid adenoma and hyperprolactinemia in the literature, reported in a patient with Costello syndrome.
 ...
PMID:A case of Costello with parathyroid adenoma and hyperprolactinemia. 1469 20

IGF-I is a key factor in intrauterine development and postnatal growth and metabolism. The secretion of IGF-I in utero is not dependent on GH, whereas in childhood and adult life, IGF-I secretion seems to be mainly controlled by GH, as revealed from studies on patients with GHRH receptor and GH receptor mutations. In a 55-yr-old male, the first child of consanguineous parents, presenting with severe intrauterine and postnatal growth retardation, microcephaly, and sensorineural deafness, we found a homozygous G to A nucleotide substitution in the IGF-I gene changing valine 44 into methione. The inactivating nature of the mutation was proven by functional analysis demonstrating a 90-fold reduced affinity of recombinantly produced for the IGF-I receptor. Additional investigations revealed osteoporosis, a partial gonadal dysfunction, and a relatively well-preserved cardiac function. Nine of the 24 relatives studied carried the mutation. They had a significantly lower birth weight, final height, and head circumference than noncarriers. In conclusion, the phenotype of our patient consists of severe intrauterine growth retardation, deafness, and mental retardation, reflecting the GH-independent secretion of IGF-I in utero. The postnatal growth pattern, similar to growth of untreated GH-deficient or GH-insensitive children, is in agreement with the hypothesis that IGF-I secretion in childhood is mainly GH dependent. Remarkably, IGF-I deficiency is relatively well tolerated during the subsequent four decades of adulthood. IGF-I haploinsufficiency results in subtle inhibition of intrauterine and postnatal growth.
 ...
PMID:Homozygous and heterozygous expression of a novel insulin-like growth factor-I mutation. 1576 76

The second half of the 20th century vastly increased the life span of those with mental retardation (MR). Today the average life expectancy of older adults with MR is 66.1 years and growing. As these individuals age, they present increasing challenges to the clinician. Increased rates of hearing and visual impairments, obesity, and osteoporosis as well as high rates of dementia with associated psychiatric problems make care for the aging individual with MR complex. Primary care providers need to be aware that elders with MR will comprise an increasing part of their practice, and that they present with many chronic conditions.
 ...
PMID:Aging with mental retardation: increasing population of older adults with MR require health interventions and prevention strategies. 1582 58

Homocystinuria is an autosomal recessive inborn error of metabolism that is most often caused by mutation in the cystathionine beta-synthase (CBS) gene. Patients may develop serious clinical manifestations such as lens dislocation, mental retardation, osteoporosis, and atherothrombotic vascular disease. Over 100 mutations have been reported, but so far, none have been reported in Korea. Mutation analysis of the CBS gene in six Korean patients with homocystinuria was performed by direct sequencing. Eight mutations were identified, including four known mutations (T257M, R336C, T353M, and G347S) and four novel mutations (L154Q, A155V, del234D, and A288T). All patients were compound heterozygotes. To characterize these mutations, normal or mutated forms of CBS were cloned into pcDNA3.1 expression vector followed by transfection into mammalian cells for transient expression. Whereas the expression levels of mutant proteins were comparable to that of normal control, enzyme activities of all the mutant forms were significantly decreased. In addition, a novel single nucleotide polymorphism, R18C, was identified, which showed one-third to two-thirds the enzyme activity of wild type and 1% of the allele frequency in normal control. The spectrum of mutations observed in Korean patients bears less resemblance to those observed in Western countries.
 ...
PMID:Identification and functional analysis of cystathionine beta-synthase gene mutations in patients with homocystinuria. 1620 33

Iodine prophylaxis in Poland started in 1997 and is based on mandatory iodzation of household salt with 20-40 mg KI/ 1 kg, supplementation of bottle fed infants with iodized formulas with 10,0 microg KI/100 ml, and a voluntary supplementation of pregnant and breast feeding women with additional 100-150 microg of iodine/ day. Last evaluation of efficacy of the iodine prophylaxis performed in 2003 by WHO and International Council for the Control of Iodine Deficiency Disorders allocated Poland within the group of the European countries with sufficient iodine supplementation on the population level. However according to data of the Institute of Mather and Chield in Poland, around 50 % of pregnant women only is additionally supplemented with iodine. Iodine deficiency during pregnancy even as a moderate iodine deficiency, creates a risk of mental retardation, perinatal complication like low and very low births weigt of neonates with increased perinatal mortality rate and late consequences in adult life: metabolic syndrom and type 2 diabetes. Another limitation of the actual model of iodine prophylaxis in Poland, it is too high consumption of natrum chloride (over 5,0 g of household salt/day/ capita). It is around 50% over WHO recommendation. Intensive preventive program against hypertension, type 2 diabetes, atherosclerosis, osteoporosis and some neoplasmatic diseases includes limitation of natrum chloride consumption- as one of the risk factors. Therefore new scope of the National Programme for Elimination of Iodine Deficiency will include: a special prorgramme for the iodization of animal food according to european standard, increased rate of pregnant women additionally supplemented with iodine, strengthening public awarness on necessary increase of milk consumption especially in pregnancy and in children and continouse monitoring system of biologic effects and technologic quality of the model of iodine prophylaxis.
 ...
PMID:[Iodine deficiency in pregnancy--a continuing public health problem]. 1633 75

The sequences of both of the human sex chromosomes and of a substantial part of the chimpanzee Y chromosome have now been determined, and most of the protein-coding genes have been identified. The X chromosome codes for more than 800 proteins but the Y chromosome for only approximately 60, illustrating their very different evolutionary histories since their origin from an autosomal pair approximately 300 million years ago and explaining their differential importance in disease. These sequences have provided the basis for understanding normal patterns of variation, such as the distribution of SNPs, and patterns of linkage disequilibrium. In addition, they have been useful for identifying variants associated with simple Mendelian disorders such as microphthalmia or mental retardation, and more complex disorders such as osteoporosis.
 ...
PMID:The sequences of the human sex chromosomes. 1665 Jul 60

The amino acid homocysteine (Hcy), formed from methionine has profound importance in health and diseases. In normal circumstances, it is converted to cysteine and partly remethylated to methionine with the help of vit B12 and folate. However, when normal metabolism is disturbed, due to deficiency of cystathionine-beta-synthase, which requires vit B6 for activation, Hcy is accumulated in the blood with an increase of methionine, resulting into mental retardation (homocystinuria type I). A decrease of cysteine may cause eye diseases, due to decrease in the synthesis of glutathione (antioxidant). In homocystinurias type II, III and IV, there is accumulation of Hcy, but a decrease of methionine, thus, there is no mental retardation. Homocysteinemia is found in Marfan syndrome, some cases of type I diabetes and is also linked to smoking and has genetic basis too. In hyperhomocysteinemias (HHcys), clinical manifestations are mental retardation and seizures (type I only), ectopia lentis, secondary glaucoma, optic atrophy, retinal detachment, skeletal abnormalities, osteoporosis, vascular changes, neurological dysfunction and psychiatric symptoms. Thrombotic and cardiovascular diseases may also be encountered. The harmful effects of homocysteinemias are due to (i) production of oxidants (reactive oxygen species) generated during oxidation of Hcy to homocystine and disulphides in the blood. These could oxidize membrane lipids and proteins. (ii) Hcy can react with proteins with their thiols and form disulphides (thiolation), (iii) it can also be converted to highly reactive thiolactone which could react with the proteins forming -NH-CO- adducts, thus affecting the body proteins and enzymes. Homocystinuria type I is very rare (1 in 12 lakhs only) and is treated with supplementation of vit B6 and cystine. Others are more common and are treated with folate, vit B12 and in selected cases as in methionine synthase deficiency, methionine, avoiding excess. In this review, the role of elevated Hcy levels in cardiovascular, ocular, neurologial and other diseases and the possible therapeutic measures, in addition to the molecular mechanisms involved in deleterious manifestations of homocysteinemia, have been discussed.
 ...
PMID:Biochemistry of homocysteine in health and diseases. 1713 33

Studies of human chromosomal aberrations and knockout (KO) mice have suggested SATB2 as a candidate gene for a human malformation syndrome of craniofacial patterning and brain development. Of 59 unrelated patients with craniofacial dysmorphism, with or without mental retardation, one 36-year-old man had a nonsynonymous mutation in SATB2. The affected individual exhibited craniofacial dysmorphisms including cleft palate, generalized osteoporosis, profound mental retardation, epilepsy and a jovial personality. He carries a de novo germline nonsense mutation (c.715C>T, p.R239X) in the exon 6 of SATB2. Expression studies showed that the mutant RNA was stable, expected to produce a truncated protein predicted to retain its dimerization domain and exert a dominant negative effect. This new syndrome is the first determined to result from mutation of a gene within the family that encodes nuclear matrix-attachment region (MAR) proteins.
 ...
PMID:Heterozygous nonsense mutation SATB2 associated with cleft palate, osteoporosis, and cognitive defects. 1737 62

We report on a 26-year-old patient presenting with extremely short stature (height 72cm, weight 6.5kg, OFC 42.5cm), facial dysmorphism, cleft lip--palate, severe mental retardation and de novo 1q24.2--q25.2 and 12q24.31 interstitial deletion. He was the only child of non-consanguineous parents and his birth length was 43cm. He had severe feeding difficulties and required enteral nutrition until the age of 3 years. Standard cytogenetic analysis showed an apparently balanced de novo translocation t(1;12)(q24;q24). Endocrine studies at 11 years of age for severe growth retardation revealed multiple pituitary hormone deficiency with severe growth hormone deficiency, but the child was untreated because of associated mental retardation. At 26 years of age, he could not walk or speak and had no signs of puberty. Investigations revealed spondylo-epi-metaphyseal dysplasia with severe osteoporosis, enlarged aorta when compared to the patient's size and apparently normal pituitary development. High resolution karyotype showed a 1q24-q25 deletion, and comparative genomic hybridization studies confirmed the 1q interstitial deletion. FISH studies of both breakpoints using PACs and BACs enabled us to further characterize the 1q interstitial deletion (1q24.2-1q25.2) and also revealed a 12q24.31 interstitial microdeletion. This case is compared with previously reported patients with similar deletions, but the untreated pituitary deficiency could also be responsible in part for the severity of the growth deficiency. This observation is of interest for two reasons. First, these deletions could be a clue in the search for a gene responsible for growth hormone deficiency/midline defects. Second, it shows the importance of molecular cytogenetics in the study of de novo apparently balanced translocation with abnormal phenotype.
 ...
PMID:Untreated growth hormone deficiency with extremely short stature, bone dysplasia, cleft lip--palate and severe mental retardation in a 26-year-old man with a de novo unbalanced translocation t(1;12)(q24;q24). 1772 Jun 46


<< Previous 1 2 3 4 5 6 Next >>