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

Glycerol kinase deficiency (GKD) has been described in isolation and in complex phenotypes including either congenital adrenal hypoplasia, Duchenne muscular dystrophy, or both. Cytogenetic and molecular studies have localized these defects to a deletion involving the X chromosome at band Xp21, consistent with its X-linked recessive pattern of inheritance. Other clinical findings in the complex glycerol kinase deficiency (CGKD) patients are mental retardation, short stature, and hypogonadotropic hypogonadism. We report on a 6-year-old boy who, in addition to the CGKD phenotype described above, had ocular hypopigmentation consistent with Forsius-Eriksson ocular albinism, also known as type 2 ocular albinism or Aland Island eye disease. Cytogenetic analysis shows an interstitial deletion in the short arm of the X-chromosome at Xp21.
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PMID:Aland Island eye disease (Forsius-Eriksson ocular albinism) and an Xp21 deletion in a patient with Duchenne muscular dystrophy, glycerol kinase deficiency, and congenital adrenal hypoplasia. 215 12

Toxoplasmic retinochoroiditis usually presents during the first three decades of life as a consequence of intra-uterine infection by Toxoplasma gondii. The ingestion of infected undercooked meat, or foodstuffs contaminated by infected cat faeces, constitute the primary sources of infection for the non-immune mother. It is thought that following congenital infection, Toxoplasma cysts remain dormant in otherwise normal retina and that acute retinochoroiditis is the result of reactivation of the parasite, perhaps by cyst rupture. Treatment is indicated for sight threatening disease and comprises anti-Toxoplasma agents. The addition of steroids may be required to diminish the inflammatory response. Photocoagulation of normal retina around focal lesions probably decreases the incidence of recurrent inflammation. Women should be advised not to eat undercooked meat and to avoid contact with cat excrement during pregnancy. These measures will decrease the incidence of both eye disease and the more severe manifestations of congenital toxoplasmosis, which include congenital abnormalities, mental retardation, hydrocephalus and blindness.
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PMID:Toxoplasmic retinochoroiditis--a historical review and current concepts. 266 25

Congenital rubella syndrome has a wide variety of severe ophthalmic and systemic complications. A worldwide rubella epidemic from 1963 to 1965 affected thousands of infants. This is a 20 year follow up study of patients with congenital rubella syndrome analysing the prevalence of ophthalmic disorders, associated systemic problems, and correlations among these defects. The authors statistically analysed 125 cases of congenital rubella seen in the Mayo clinic ophthalmology department over a 32 year interval. Most patients were young adults. Ocular disease was the most commonly noted disorder (78%), followed by sensorineural hearing deficits (66%), psychomotor retardation (62%), cardiac abnormalities (58%), and mental retardation (42%). Multiorgan disease was typical (88%). Ocular disease and hearing loss were frequently associated (53% had both) but not significantly correlated. A similar association existed between ocular and cardiac disease. Cataracts and microphthalmia were significantly correlated with poor visual acuity (each p < 0.0001). Glaucoma was significantly correlated with cataracts (p = 0.0002) and microphthalmia (p = 0.0024) but not poor visual acuity. Four patients with microphthalmia developed late onset glaucoma. No significant association was found between gestational age at time of maternal infection and the incidence of individual ocular conditions. However, several cardiac disorders were significantly associated with gestational age. Although new cases of congenital rubella are rare, surviving victims continue to challenge the ophthalmic and medical communities with a wide range of ocular and systemic disorders.
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PMID:Congenital rubella syndrome: ophthalmic manifestations and associated systemic disorders. 811 Jul 9

Xp21 microdeletion syndrome is associated with variable size Xp21 deletions that usually include the glycerol kinase locus. The clinical phenotypes we studied in this chromosome region include: Xpter - Aland Island eye disease (AIED) -adrenal hypoplasia (AH) -glycerol kinase (GKD) -Duchenne muscular dystrophy (DMD) -retinitis pigmentosa (RP) -ornithine transcarbamylase (OTC) -centromere. In a compilation of 18 individuals in 14 families with the AH, GKD, and DMD loci deleted, 17 were male and all were developmentally delayed. In contrast, we report mentally retarded female carriers in two Xp21 deletion syndrome families with DMD, GKD, and AH in affected males. In the first family with normal karyotypes, a submicroscopic deletion was associated with DMD in the retarded male and with retardation in carrier females. In the second family an X chromosome with a cytogenetically deleted Xp21 distal to the OTC and RP genes segregated in the affected male and retarded female carriers. DNA analysis at the DMD locus verified the cytogenetic findings. This report of mental retardation in otherwise asymptomatic female carriers of Xp21 deletion classifies one form of mental retardation in females.
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PMID:Mental retardation locus in Xp21 chromosome microdeletion. 835 5

The Norrie disease and MAO genes are tandemly arranged in the p11.4-p11.3 region of the human X chromosome in the order tel-MAOA-MAOB-NDP-cent. This relationship is conserved in the mouse in the order tel-MAOB-MAOA-NDP-cent. The MAO genes appear to have arisen by tandem duplication of an ancestral MAO gene, but their positional relationship to NDP appears to be random. Distinctive X-linked syndromes have been described for mutations in the MAOA and NDP genes, and in addition, individuals have been identified with contiguous gene syndromes due to chromosomal deletions which encompass two or three of these genes. Loss of function of the NDP gene causes a syndrome of congenital blindness and progressive hearing loss, sometimes accompanied by signs of CNS dysfunction, including variable mental retardation and psychiatric symptoms. Other mutations in the NDP gene have been found to underlie another X-linked eye disease, exudative vitreo-retinopathy. An MAOA deficiency state has been described in one family to date, with features of altered amine and amine metabolite levels, low normal intelligence, apparent difficulty in impulse control and cardiovascular difficulty in affected males. A contiguous gene syndrome in which all three genes are lacking, as well as other as yet unidentified flanking genes, results in severe mental retardation, small stature, seizures and congenital blindness, as well as altered amine and amine metabolites. Issues that remain to be resolved are the function of the NDP gene product, the frequency and phenotype of the MAOA deficiency state, and the possible occurrence and phenotype of an MAOB deficiency state.
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PMID:Norrie disease and MAO genes: nearest neighbors. 854 72

Aniridia is a congenital eye disorder with a variable degree of hypoplasia or absence of iris tissue. It is caused by loss of function of the PAX6 gene and may be an isolated ocular abnormality or part of a syndrome. WAGRO refers to a rare genetic condition leading to Wilms tumor, aniridia, genitourinary anomalies, mental retardation, and obesity and is caused by a deletion of the short arm of chromosome 11 (11p), where the PAX6 gene is located. Here, we report on an 8-year-old boy with aniridia, polar cataract, and lens subluxation along with neuropsychomotor and speech delays. Karyotype evaluation showed an interstitial deletion including region 11p13-p14, confirming the diagnosis of WAGRO syndrome. In cases of aniridia, a diagnosis of WAGRO syndrome should be considered.
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PMID:WAGRO syndrome: a rare genetic condition associated with aniridia and additional ophthalmologic abnormalities. 3111 17

Purpose: Aniridia is a rare congenital eye disease, characterized by a constellation of symptoms including hypoplastic irides, foveal hypoplasia, early cataract, corneal stem cell deficiency, and glaucoma. Large chromosomal deletions spanning the PAX6 gene cause WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and intellectual disability [formerly called mental retardation]). We describe clinical and genetic studies of a three-generation pedigree with aniridia along with additional systemic conditions (morbid obesity, diabetes) suggesting the possibility of a contiguous-gene syndrome like WAGR.Methods: Clinical records were obtained and DNA was prepared from blood samples from three of the four patients and tested for mutations in the coding sequences of the PAX6 gene. The index patient also had cardiomyopathy and was tested for known cardiomyopathy genetic mutations using a next-generation DNA sequencing assay.Results: We discovered a novel intragenic PAX6 mutation, a 16 bp heterozygous deletion c.203delCCAGGGCAATCGGTGG, with Sanger sequencing that is the likely cause of autosomal dominant aniridia in this pedigree. This PAX6 deletion causes a frameshift in predicted protein translation and a subsequent premature termination, p.Pro68Leufs*6. The PAX6 deletion was detected in all three available family members with aniridia, the index patient, his mother, and his maternal aunt but was not observed in the Exome Aggregation Consortium (ExAC) database. Targeted sequencing of known cardiomyopathy genes in the index patient identified a second mutation, a 1.7 Mp deletion that spans the MYBPC3 gene.Conclusions: We report a pedigree with aniridia and other systemic abnormalities that were initially suspicious for a contiguous-gene syndrome like WAGR. However, genetic analysis of the pedigree revealed two independent genetic abnormalities on chromosome 11p: 1) a novel PAX6 mutation, and 2) a large chromosome deletion spanning MYBPC3, a known cardiomyopathy gene. It is unclear if morbid obesity and type II diabetes mellitus have a related genetic cause.
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PMID:Novel Intragenic PAX6 Deletion in a Pedigree with Aniridia, Morbid Obesity, and Diabetes. 3136 67