Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cri-du-chat syndrome is a contiguous gene syndrome that results from a deletion of the short arm of chromosome 5 (5p). Patients present with a cat-like cry at birth, which is usually considered diagnostic of this syndrome. Additional features of the syndrome include failure to thrive, microcephaly, hypertelorism, epicanthal folds, hypotonia, and severe mental retardation. We report on four families in which patients with 5p deletions have only the characteristic cat-like cry, with normal to mildly delayed development. The precise locations of the deletions in each family were determined by FISH using lambda phage and cosmid clones. All of the deletion breakpoints map distal to a chromosomal region that is implicated with the facial features and severe mental and developmental delay in the cri-du-chat syndrome. DNA clones mapping in the chromosomal region associated with the cat-like cry feature will be useful diagnostic tools. They will allow for the distinction between 5p deletions that will result in the severe delay observed in most cri-du-chat syndrome patients and those deletions that result in the isolated cat-like cry feature, which is associated with a better prognosis.
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PMID:Evidence for a distinct region causing a cat-like cry in patients with 5p deletions. 776 63

The critical importance of dosage compensation is underscored by a novel human syndrome ("XYXq syndrome") in which we have detected partial X disomy, demonstrated supernormal gene expression resulting from the absence of X inactivation, and correlated this overexpression with its phenotypic consequences. Studies of three unrelated boys with 46,XYq- karyotypes and anomalous phenotypes (severe mental retardation, generalized hypotonia and microcephaly) show the presence of a small portion of distal Xq on the long arm of the Y derivative. Cells from these boys exhibit twice-normal activity of glucose-6-phosphate dehydrogenase, a representative Xq28 gene product. In all three cases, the presence of Xq DNA on a truncated Y chromosome resulted from an aberrant Xq-Yq interchange occurring in the father's germline.
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PMID:Xq-Yq interchange resulting in supernormal X-linked gene expression in severely retarded males with 46,XYq- karyotype. 787 66

Mutation of mitochondrial (mt) DNA at nucleotide (nt) 8993 has been reported to cause neurogenic weakness, ataxia, retinitis pigmentosa (NARP), or Leigh syndrome (LS). We report a family in whom the mutation was expressed clinically as LS and hypertrophic cardiomyopathy (CMP) in a boy who presented with a history of developmental delay and hypotonia, and who had recurrent lactic acidosis. The mother's first pregnancy resulted in the birth of a stillborn female; an apparently healthy older brother had died suddenly (SIDS) at age 2 months. MtDNA analysis identified the presence of the T8993G point mutation, which was found to be heteroplasmic in the patient's skeletal muscle (90%) and fibroblasts (90%). The identical mutation was present in leukocytes (38%) isolated from the mother, but not from the father or maternal grandmother. Our findings expand the clinical phenotype of the nt 8993 mtDNA mutation to include hypertrophic cardiomyopathy and confirm its cause of LS.
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PMID:Leigh syndrome and hypertrophic cardiomyopathy in an infant with a mitochondrial DNA point mutation (T8993G). 804 71

A 73-year-old woman (patient 1) developed progressive mental deterioration at age 63, and seizures at age 70. On examination, she showed severe dementia, tonic clonic convulsion, hypotonia and muscular wasting. There was neither myoclonus nor cerebellar ataxia. Brain CT revealed a low density area in the right occipital lobe. A 44-year-old man (son of the patient 1) developed unsteady gait at age 15, muscle twitching at age 18 and then noticed speech disturbance at age 35. He had no history of convulsive seizure. Neurological examination showed cerebellar ataxia, myoclonus in the extremities and mild muscular weakness. His intelligence was normal. Brain CT showed moderate atrophy of the pons and the cerebellum. Both cases showed the same mitochondrial DNA mutation as reported previously in patients with MERRF. However, the clinical features, the age of onset and the brain CT findings were totally different between these 2 cases. In the progress of mitochondrial genetic analysis, atypical forms in MERRF like the patient 1 would increase in number, and the wide variation of clinical symptoms should be considered.
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PMID:[Two cases of MERRF (myoclonus epilepsy associated with ragged red fibers) showing different clinical features in the same family]. 812 82

Lissencephaly ("smooth brain") is a brain malformation characterized by a smooth cerebral surface, incomplete neuronal migration, and secondary abnormalities such as mental retardation, seizures, and minor facial dysmorphisms. Recent reports have produced evidence supporting several different causes including submicroscopic deletions in chromosome band 17p13.3, autosomal recessive inheritance, intrauterine infection, and intrauterine perfusion failure. We describe the clinical manifestations in seven patients with lissencephaly, and review pertinent studies regarding possible causes. The clinical manifestations were uniformly severe. All patients had severe mental retardation, hypotonia, often combined with spastic paralysis, and infantile spasms which did not respond to treatment. Most had poor growth, postnatal microcephaly, feeding problems, and frequent respiratory infections including pneumonia. None had other significant birth defects. Appropriate studies include computed tomography or magnetic resonance imaging (sometimes both), chromosome analysis, DNA analysis of the lissencephaly region on chromosome 17, electroencephalography and sometimes metabolic studies.
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PMID:Clinical manifestations and evaluation of isolated lissencephaly. 830 52

Robertsonian translocations are usually ascertained through abnormal children, making proposed phenotypic effects of apparently balanced translocations difficult to study in an unbiased way. From molecular genetic studies, though, some apparently balanced rearrangements are now known to be associated with phenotypic abnormalities resulting from uniparental disomy. Molecular explanations for other cases in which abnormality is seen in a balanced translocation carrier are being sought. In the present paper, an infant is described who has retarded growth, developmental delay, gross muscular hypotonia, slender habitus, frontal bossing, micrognathia, hooked nose, abundant wispy hair, and blue sclerae. Cytogenetically, she appeared to be a carrier of a balanced, paternally derived 14;21 Robertsonian translocation. Analysis of DNA polymorphisms showed that she had no paternal allele at the D14S13 locus (14q32). Study of additional DNA markers within 14q32 revealed that her previously undescribed phenotype results from an interstitial microdeletion within 14q32. Fluorescent in situ hybridization was used to show that this microdeletion had occurred de novo on the Robertsonian translocation chromosome. These observations may reactivate old suspicions of a causal association between Robertsonian translocations and de novo rearrangements in offspring; a systematic search for similar subcytogenetic rearrangements in other families, in which there are phenotypically abnormal children with apparently balanced translocations, may be fruitful. The clinical and molecular genetic data presented also define a new contiguous gene syndrome due to interstitial 14q32 deletion.
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PMID:De novo microdeletion on an inherited Robertsonian translocation chromosome: a cause for dysmorphism in the apparently balanced translocation carrier. 835 73

We report the case of a 5-year-old girl with severe developmental disabilities, skeletal anomalies, hypotonia, rectal atresia, malrotation of the intestine, horseshoe kidney, vesicoureteric reflux, and minor facial anomalies. Conventional cytogenetic techniques suggested that she had a mosaic 46,XX/47,XX,+i(8p) constitution, and the identity of the isochromosome was confirmed by in situ hybridization and chromosome painting. Polymorphic DNA markers are consistent with the i(8p) having arisen as the result of a segregation error and centromere misdivision at the second maternal meiotic division. The i(8p) was seen in 17/25 (68%) lymphocytes at the age of one month but had declined to 31/100 (31%) cells by the age of 5 years. At this time the i(8p) was seen in 30/68 (44%) cultured skin fibroblasts. The proposita had an approximately twofold increase in red cell glutathione reductase activity but a normal level of tissue-plasminogen activator. These enzyme results are consistent with the known localisation of the glutathione reductase gene on the short arm of chromosome 8 but suggest that the tissue-plasminogen activator gene may map outside this region.
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PMID:Mosaic tetrasomy 8p: molecular cytogenetic confirmation and measurement of glutathione reductase and tissue plasminogen activator levels. 836 38

A special subphenotype of the fragile X syndrome is reported which is characterised by extreme obesity with a full, round face, small, broad hands/feet, and regional skin hyperpigmentation. It resembles the Prader-Willi syndrome (PWS) and might therefore be named 'Prader-Willi-like'. Unlike the PWS, these PW-like fragile X patients lack the neonatal hypotonia with feeding problems during infancy followed by hyperphagia from toddlerhood. We describe five new fragile X patients and present a clinical update of three previously described patients with the PW-like phenotype. In one family, segregation of either the classical Martin-Bell or the PW-like phenotype was observed and in another family there was repeated transmission of the PW-like phenotype. Previously, one of the patients had been misdiagnosed as having classical PWS, based on clinical findings. Molecular studies of the FMR-1 gene showed the typical full mutations as seen in fragile X syndrome males. Molecular analysis of the 15q11-13 region, which is deleted in the majority of classical PWS patients, did not show any detectable abnormalities. In a group of 26 patients with suspected Prader-Willi syndrome but without detectable molecular abnormalities of chromosome 15, one fragile X patient was found. These clinical and molecular findings illustrate the necessity to perform DNA analysis of the FMR-1 gene in mentally retarded patients presenting with a PW phenotype but without the PWS specific cytogenetic/molecular abnormalities of chromosome 15.
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PMID:Clinical and molecular studies in fragile X patients with a Prader-Willi-like phenotype. 801 84

The X-linked recessive centronuclear/myotubular myopathy (XLR-CNM/MTM1), a severe neonatal disorder characterized by generalized hypotonia, muscle weakness, and primary asphyxia, has recently been mapped to Xq28. This report presents the first four prenatal diagnoses of XLR-CNM using DNA markers of the Xq28 region. The analyses of one female and three male fetuses revealed maternal transmission of the XLR-CNM-associated alleles in all four cases. Two of the male fetuses have been aborted, and the pregnancies of the third male and the female fetuses have been continued. The diagnosis of XLR-CNM at the birth of the third boy, as well as the pathologic findings in the muscle of one of the aborted fetuses, confirmed the linkage results of the prenatal analyses. Our findings prove the DNA markers St14, cpX67, DX13, and pSt35-691 to be useful in prenatal diagnosis of XLR-CNM and present the possibility to confirm the diagnosis by histologic examination of the first-trimester abortus. This permits an indirect prenatal diagnosis of XLR-CNM in chorionic villus biopsies at 9 to 12 wk gestation, using DNA-based linkage analyses allowing early termination of an affected pregnancy.
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PMID:Prenatal diagnosis of X-linked centronuclear myopathy by linkage analysis. 843 96

We studied a patient with Leigh's syndrome using neurophysiologic, radiologic, enzymatic, biochemical, and molecular analysis. Her clinical course had started with acute encephalopathic symptoms at 7 months of age. With repeated remission and exacerbation, she developed hypotonia and symptoms of brainstem dysfunction, such as irregular respiration and swallowing difficulty. These symptoms were followed by epileptic seizures, including simple partial seizures and tonic spasms. Both serum lactate and serum pyruvate levels were elevated, and deficient activity was detected in cytochrome c oxidase in her quadriceps femoris muscle. From the early stages, we noted an abnormality in the auditory brainstem response and visual evoked potentials, and an abnormal symmetrical low-density area in the basal ganglia on the computed tomographic scan. We found a mitochondrial DNA point mutation at 8993 in blood samples from both the patient and her mother using a simple polymerase chain reaction method. The ratio of wild and mutant mitochondrial DNA calculated densitometrically on polymerase chain reaction products was 56.6% in the patient's blood cells and 8.4% in her mother's. This patient's disorder was thought to be maternally inherited Leigh's syndrome. Her brother had died of the identical clinical features at 1 year 9 months of age.
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PMID:A T-to-G mutation at nucleotide pair 8993 in mitochondrial DNA in a patient with Leigh's syndrome. 850 74


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