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)

Darier's disease is determined by an autosomal dominant gene and is clinically characterized by confluent hyperkarotic papules. Mental retardation may appear in up to 10-20% of patients. Convulsions, spinocerebellar tract degeneration, polyneuropathy, psychiatric disorders and cerebral atrophy occur with a low and as yet not precisely determined incidence. In the medical literature reviewed only two previous cases of cerebral atrophy associated with Darier's disease were found. This study describes six members of a family affected with an unusually high incidence of neurologic manifestations. The mother and her five sons showed skin lesions, which, on histological examination, revealed the characteristic pathological changes of Darier's disease. Two of the five siblings with convulsions and mental retardation underwent computed tomography of the brain and both patients revealed the classic findings in atrophy; moderate enlargement of the lateral ventricles and widening of the cortical sulci. Cerebral atrophy was correlated with mental retardation and convulsions.
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PMID:[Mental retardation convulsions and cerebral atrophy; main neurological changes in Darier's disease]. 739 29

Darier's disease is a rare autosomal dominant skin disorder in which there is abnormal adhesion between keratinocytes. It appears to be associated with an increased prevalence of neuropsychiatric disorders including mental retardation and epilepsy. In addition we have previously reported a family in which major affective disorder cosegregates with Darier's disease. In the present study we have localized the gene for Darier's disease to chromosome 12q23-q24.1 by linkage analysis in five British pedigrees. We obtained a maximum two point lod score of 4.29 with marker D12S84 at zero recombination fraction. All five families showed evidence of linkage between the disease gene and markers in this region. Subsequent identification of the Darier's disease gene will provide insights into normal mechanisms of cell adhesion and may be of importance in the genetic investigation of neuropsychiatric disorders as well as elucidating the pathogenesis of Darier's disease itself.
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PMID:The gene for Darier's disease maps to chromosome 12q23-q24.1. 828 Nov 34

There are some reports in the literature about the comorbidity of Darier's Disease (keratosis follicularis) and psychiatric illness (e.g. mental retardation or affective disorders). Here we present evidence that schizophreniform psychosis may also be associated with Darier's Disease.
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PMID:Darier's Disease and psychosis. 894 98

Darier's disease (DD) is a rare, dominantly inherited disorder that affects the skin producing a variety of types of lesion. Close examination of lesional DD skin shows the presence of abnormal keratinization (epidermal differentiation) and acantholysis (loss of cohesion) of keratinocytes. A number of clinical studies have described the co-occurrence of various neurological and psychiatric symptoms with DD, including mood disorders, epilepsy, mental retardation and a slowly progressive encephalopathy. A single locus for DD has been mapped to chromosome 12q23-q24.1, and a variety of missense, nonsense, frameshift and splicing mutations in the ATP2A2 gene have been described recently in families with DD. This gene encodes the sarcoplasmic/endoplasmic reticulum calcium-pumping ATPase SERCA2, which has a central role in intra-cellular calcium signalling. In this study, we performed mutation analysis on ATP2A2 in 19 unrelated DD patients, of whom 10 had neuropsychiatric phenotypes. We identified and verified 17 novel mutations predicting conservative and non-conservative amino acid changes, potential premature translation terminations and potential altered splicing. Our findings confirm that mutations in ATP2A2 are associated with DD. In neuropsychiatric cases, there was a non-random clustering of mutations in the 3' end of the gene ( P = 0.01), and a predominance of the missense type (70% versus 38% in DD patients). This supports the hypothesis that the DD gene has pleiotropic effects in brain and that mutations in SERCA2 are implicated in the pathogenesis of neuropsychiatric disorders.
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PMID:ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes. 1044 25

A 22 year-old Saudi patient is reported who had Darier-White disease (Keratosis follicularis), presenting with the classical cutaneous manifestation of this disease in addition to systemic symptoms, including chronic renal failure, mental retardation, epilepsy, cataract and corneal opacities.
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PMID:Darier-White disease in a Saudi patient associated with systemic involvement. 1045 71

Darier's disease, also known as keratosis follicularis, is an uncommon autosomal dominant disorder that may also occur as a sporadic mutation. It is characterized by multiple eruptions of hyperkeratotic or crusted papules at seborrheic areas with histologic acantholysis and dyskeratosis. It usually begins in the first or second decade of life and is equally prevalent in men and women. Darier's disease is caused by mutations in the ATP2A2 gene, which maps to chromosome 12q23-q24.1 and encodes the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2). The co-occurrence of various neurologic and psychiatric diseases with Darier's disease has been reported, including mood disorders, epilepsy, mental retardation, slowly progressive encephalopathy, and schizophrenia. Linkage studies using the association between these disorders and Darier's disease to determine the gene locus of these psychiatric disorders inferred the presence of a bipolar susceptibility gene on chromosome 12q23-q24.1 in the region of the Darier's disease gene (DAR). We report a case of Darier's disease of more than 40 years' duration and bipolar I disorder of 30 years' duration in a 52-year-old man, and provide a brief review of the literature.
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PMID:Darier's disease associated with bipolar affective disorder: a case report. 1267 38

Congenital bilateral anophthalmia and microphthalmia are rare conditions, with overall prevalence in one study set at 1.0 per 10,000 births. We report here a case of congenital bilateral severe microphthalmia with mental retardation and cerebral palsy. The patient was man aged 38 years with a chromosome aberration, namely a balanced translocation: 46, XY, t (2;6)(q31;q24). He had no other malformations apart from the severe microphthalmia. CT of the head showed no significant abnormal findings in the brain, but rudimentary eyeballs and external ocular muscles in the bilateral orbits. There was no family history of anophthalmia, microphthalmia, mental retardation or cerebral palsy. His mother had not used any medications or excessive alcohol during gestation. Putative genes of anophthalmia and microphthalmia reported to date include PAX6 (Glaser T et al 1994) and CHX10 (Ferda Percin E et al 2000). Further, some loci of these conditions have been reported (Graham CA et al 1991; Bessant DAR et al 1998; Morle L et al 2000: Forrester S et al 2001: Ng D et al 2002). To our knowledge, however, this is the first report of nonsyndromic microphthalmia or anophthalmia with chromosome 2q31 or 6q24 aberration. We consider that the putative gene may be located on the brake points of chromosome 2 and 6.
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PMID:Congenital bilateral severe microphthalmia with mental retardation and cerebral palsy: chromosome aberration, 46, XY, t (2;6)(q31;q24). 1611 96