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)

Autosomal recessive cutis laxa (ARCL) describes a group of syndromal disorders that are often associated with a progeroid appearance, lax and wrinkled skin, osteopenia and mental retardation. Homozygosity mapping in several kindreds with ARCL identified a candidate region on chromosome 17q25. By high-throughput sequencing of the entire candidate region, we detected disease-causing mutations in the gene PYCR1. We found that the gene product, an enzyme involved in proline metabolism, localizes to mitochondria. Altered mitochondrial morphology, membrane potential and increased apoptosis rate upon oxidative stress were evident in fibroblasts from affected individuals. Knockdown of the orthologous genes in Xenopus and zebrafish led to epidermal hypoplasia and blistering that was accompanied by a massive increase of apoptosis. Our findings link mutations in PYCR1 to altered mitochondrial function and progeroid changes in connective tissues.
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PMID:Mutations in PYCR1 cause cutis laxa with progeroid features. 1964 21

Geroderma osteodysplasticum is a rare autosomal recessive disorder characterized by wrinkled skin on the dorsum of the hands and feet, osteopenia, prognathism, and an elongated and lax face. The mutated gene was identified as GORAB (SCYL1BP1). As well, the PYCR1 gene also was shown to be mutated in a similar disease, designated cutis laxa, autosomal recessive, type IIB (ARCL2B) or cutis laxa with progeroid features. We describe here the clinical findings in four affected individuals in a family with geroderma osteodysplasticum with mental retardation and a homozygous mutation in PYCR1. Although the disease resulting from recessive mutations in that gene has been recently designated ARCL2B, some clinical features, such as prognathism, elongated and lax face, osteopenia and limitation of skin wrinkling to the dorsum of hands and feet, in the patients reported here as well as in others reported with PYCR1 mutations, are generally more common in geroderma osteodysplasticum resulting from recessive GORAB mutations. While the patients with GORAB mutations have severe osteopenia, the patients with PYCR1 mutations have severe mental retardation. In conclusion, the phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than ARCL2B.
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PMID:The phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than autosomal recessive cutis laxa type 2. 2183 30

Cutis laxa is a connective tissue disorder caused by deficiency of fibro elastic plexus, which can involve multiple organs. It is inherited in autosomal dominant, autosomal recessive, and X-linked. Autosomal recessive cutis laxa type 2, which appears to compromise a spectrum of disorders, starts with severe wrinkly skin syndrome and leads to more severe diseases related to growth and developmental delays and skeletal anomalies. The clinical manifestations in some of cases of Cutis laxa consist of redundant loose skin, pre-and post-natal growth deficiency, mental retardation, large fontanels, and dislocation of the hips. The authors present the case of a female patient with involved internal organ disorder and delay in growth in addition to skin laxity in which gene sequence analysis of PYCR1 indicated C.797G>A mutation.
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PMID:Congenital Cutis Laxa Type 2 Associated With Recurrent Aspiration Pneumonia and Growth Delay: Case Report. 2651 48

Aging is a natural process that internal gene control and external stimuli mediate. Clinical data pointed out that homozygotic or heterozygotic mutation in the pyrroline-5-carboxylate reductase 1 (PYCR1) gene in humans caused cutis laxa (ARCL) disease, with progeroid appearance, lax and wrinkled skin, joint laxity, osteopenia, and mental retardation phenotypes. In this study, we aimed to generate pycr1 knockout (KO) zebrafish and carried out biochemical characterizations and behavior analyses. Marked apoptosis and senescence were detected in pycr1 KO zebrafish, which started from embryos/larvae stage. Biochemical assays showed that adult pycr1 KO fish have significantly reduced proline and extracellular matrix contents, lowered energy, and diminished superoxide dismutase (SOD) and telomerase activity when compared to the wild type fish, which suggested the pycr1 KO fish may have dysfunction in mitochondria. The pycr1 KO fish were viable; however, displayed progeria-like phenotype from the 4 months old and reach 50% mortality around six months old. In adult stage, we found that pycr1 KO fish showed reduced locomotion activity, aggression, predator avoidance, social interaction interest, as well as dysregulated color preference and circadian rhythm. In summary, we have identified multiple behavioral alterations in a novel fish model for aging with pycr1 gene loss-of-function by behavioral tests. This animal model may not only provide a unique vertebrate model to screen potential anti-aging drugs in the future, but also be an excellent in vivo model towards a better understanding of the corresponding behavioral alterations that accompany aging.
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PMID:Zebrafish Carrying pycr1 Gene Deficiency Display Aging and Multiple Behavioral Abnormalities. 3109 4