Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Emery-Dreifuss muscular dystrophy (EDMD) is an inherited disorder characterized by the clinical triad of life-threatening progressive cardiomyopathy with conduction defect, early onset joint contractures and slow progressive muscle weakness in scapulo-humero-peroneal distribution. Cardiomyopathy in EDMD is usually noticed after the second to third decade of life, and becomes worse with age. Permanent auricular paralysis occurs frequently and is considered a hallmark of EDMD cardiomyopathy. Cardiac involvement may also occur in female carriers. In autopsy cases, enlargement of the atria with remarkable thinning have been observed. Identification of the gene responsible for X-linked EDMD (X-EDMD) and the protein product, emerin, provided a diagnostic clue for EDMD. Since the emerin gene is rather small, the entire sequence can easily be surveyed. Western blot and immunohistochemistry show an absence of emerin in muscle and skin tissues and oral exfoliating cells in male patients with X-EDMD, and a reduction of the protein content with a mosaic expression pattern in female carriers. Emerin anchors at the inner nuclear membrane of cardiac, skeletal and smooth muscles, and interacts with lamins and nucleoplasm, thereby possibly maintaining the mechanical stability of the nuclear membrane of muscle cells that shows rigorous contraction/relaxation. More recently, positive emerin staining at the cardiac demosomes and fasciae adherentes was noticed in addition to the specific localization at the inner nuclear membrane. This localization implies a physiological role for the protein in cardiac conduction.
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PMID:Emerin and cardiomyopathy in Emery-Dreifuss muscular dystrophy. 1022 Aug 66

Previous series that described phenotypes in carriers of Alport's syndrome did not distinguish genetically between carriers of X-linked and autosomal recessive disease. In this study, modes of inheritance in unselected families with Alport's syndrome associated with two city and two provincial hospitals were determined using microsatellite markers, and carriers of disease haplotypes were identified within these families. All 47 carriers (100%) from 18 families with X-linked Alport's syndrome had dysmorphic hematuria on phase-contrast microscopy, but few developed renal failure (3 of 40 carriers; 8%), clinical hearing loss (2 of 45 carriers; 4%), retinopathy (1 of 30 carriers; 3%), or lenticonus (0 of 30 carriers; 0%). Eleven of the 14 carriers (79%) from 2 families with autosomal recessive disease had dysmorphic hematuria, but none had renal failure, clinical hearing loss, retinopathy, or lenticonus. Urinary red blood cell counts in carriers of X-linked Alport's syndrome were greater than those in carriers of autosomal recessive disease (P < 0.0001), but the frequency of proteinuria and hypertension and levels of proteinuria were not different. There was more tubulointerstitial damage in carriers of X-linked disease (P = 0.012); however, carriers of autosomal recessive disease had more widespread and more uniform thinning of the glomerular basement membrane (P < 0.0001) and less lamellation (P < 0.04).
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PMID:A comparison of the clinical, histopathologic, and ultrastructural phenotypes in carriers of X-linked and autosomal recessive Alport's syndrome. 1172 53

Thin basement membrane nephropathy (TBMN) is a glomerular disorder characterized clinically by isolated hematuria and pathologically by diffuse thinning of the glomerular basement membrane (GBM) on ultrastructural examination. The pathologic diagnosis of TBMN is problematic, in part because of the wide range of GBM thicknesses in the normal population. GBM thickness varies with age, sex, and the different methods of tissue preparation and measurement. In addition, there are no standardized diagnostic criteria defining the degree or extent of GBM thinning required for the diagnosis of TBMN. GBM thinning is often seen in other glomerulopathies, where it may represent an overlap with TBMN or may be secondary to GBM damage and remodeling. Importantly, TBMN must be differentiated from the GBM thinning seen in some renal biopsy specimens from boys and female heterozygotes with X-linked Alport syndrome because of the very different prognoses of these two conditions.
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PMID:Pathology of thin basement membrane nephropathy. 1588 Mar 25

The clinical implications of thin basement membrane nephropathy (TBMN) in renal transplantation must be considered from the perspectives of both the allograft recipient and the donor. Most individuals with TBMN have a benign course, but some develop end-stage renal failure (ESRF) and undergo transplantation. ESRF in patients with TBMN often results from the presence of additional glomerular or interstitial lesions and some of these, such as immunoglobulin (Ig)A disease, may recur in the renal allograft and affect outcome. In addition, individuals with TBMN always must be distinguished from those with glomerular membrane thinning due to Alport syndrome. This is not only to enable appropriate genetic counseling but also to anticipate the possible complication of posttransplant anti-glomerular basement membrane disease. From the perspective of the live renal donor, donation from individuals with TBMN (or carriers of X-linked Alport syndrome with thinned membranes) remains controversial because the risks remain unknown. Any effects of the thinned membranes themselves on allograft function are unclear. Further advances in our understanding of the clinical, pathologic, and molecular features of TBMN should result in improved assessment of potential live donors and help stratify those at risk for renal impairment.
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PMID:Thin basement membrane nephropathy and renal transplantation. 1588 Mar 31

Alport syndrome (ATS) is a clinically and genetically heterogeneous progressive nephropathy often associated with deafness and/or ocular lesions. The histological aspect is characterized by thinning, thickening and splitting of the glomerular basement membrane (GBM). Alport syndrome is caused by mutations in COL4A3 gene (type IV collagen, alfa-3 chain), or COL4A4 gene (type IV collagen, alfa-4 chain) or COL4A5 gene (type IV collagen, alfa-5 chain) genes. Alport syndrome accounts for 1-2% of renal failure cases in Europe, and for 2-3% of transplanted patients in United States. This review focuses on the three types of Alport syndrome which differ in the clinical progression and in the mode of inheritance. The common X-linked form is caused by mutations in the COL4A5 gene and it accounts for 85% of cases. The autosomal dominant and the autosomal recessive forms are caused by mutations in either COL4A3 or COL4A4 genes. The autosomal recessive form which is responsible for the 10-15% of Alport cases, has been known since several years. On the contrary, the autosomal dominant form has only recently been identified in some families. Furthermore, this review will focus on the difficulties encountered during the genetic counselling related to the differential diagnosis between Alport syndrome and Thin Basement Membrane Disease (TBMD). We will report direct experiences of our group showing the difficulties to give an exact prognosis and a correct recurrence risk to the family.
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PMID:[Clinical and genetic features of the Alport 'syndromes']. 1626 4

Coffin-Lowry syndrome (CLS) is an X-linked mental retardation syndrome caused by defects in the RSK2 gene. We have identified a CLS family with four patients in two generations. The patients in this family, a mother and her three children (a male and two females), all have severe mental retardation with the typical CLS phenotype. In addition, brain MRI studies on the three siblings revealed abnormalities in deep subcortical white matter, thinning of the corpus callosum, hypoplastic cerebellar vermis, and asymmetry of the lateral ventricles. The degree of severity of the MRI findings correlated with the severity of mental retardation in the patients. Extensive mutation screening was performed on the entire RSK2 gene in this family. Twenty-two exons including the intron/exon junctions were amplified by PCR and subsequently sequenced on both strands. A novel mutation, a two-nucleotide insertion (298 ins TG), was identified. The insertion creates a stop codon at codon 100, resulting in a 99 amino acid truncated RSK2 protein. All patients tested have the same mutation, and no other mutation could be found in the RSK2 gene from the proband. The mutation was confirmed by PCR/RFLP. X-chromosome inactivation assay on the female patients revealed significant skewing toward inactivation of the normal RSK2 allele. Thus, this novel mutation is likely to be responsible for the unusual clinical presentation in this family, which includes full phenotypic expression in females and unique brain MRI abnormalities. The pathological function of the mutation and genotype/phenotype correlation between the mutation and this unusual clinical presentation await further clarification.
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PMID:A novel RSK2 (RPS6KA3) gene mutation associated with abnormal brain MRI findings in a family with Coffin-Lowry syndrome. 1669 78

Alport Syndrome (AS) is an inherited disorder of the glomerular basement membrane (GBM) transmitted as an X-linked dominant form in approximately 80% of patients. This X-linked form is caused by mutations in the collagen type IV alfa 5 gene (COL4A5) located on chromosome X; in the remainder of the cases, the autosomal, mostly recessive form, results from mutations in the collagen type IV alfa 3 gene (COL4A3) or alfa 4 gene (COL4A4) located on the 2q. Diagnostic lesions can be observed by electron microscopy (EM) and are characterized by thinning, thickening and/or splitting of the GBM. Isolated thinning of the GBM is usually associated with isolated microhematuria, a non progressive condition which has often a familial trait. Skin biopsy has also recently emerged to be a valuable alternative for the diagnosis of X-linked AS, because the alfa 5 (COL4A5) chain is also expressed in the epidermal basement membrane. A reliable diagnosis can often be achieved through combined renal and cutaneous immunohistochemical analysis, even in patients with limited clinical signs or atypical histological findings, and/or without suggestive family history. The present case report is an example of such diagnostic dilemma, where these techniques allowed to make a diagnosis despite contradictive clinical and histological features in contrast with a positive family history of renal disease.
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PMID:[Thin basement membrane and Alport syndrome]. 1712 66

Alport syndrome (AS) is the most common form of hereditary nephritis. Females with X-linked AS are heterozygous carriers of the disease mutation. Carrier status in females without a family history has traditionally been diagnosed by kidney biopsy; more recently skin biopsy has been utilized. We report on a 14-year-old girl with long-standing hematuria and intermittent proteinuria who underwent kidney and skin biopsy to establish a definitive diagnosis. Electron microscopy showed extensive thinning of glomerular basement membrane (GBM), with no evidence of lamination. Immunofluorescence staining showed continuous GBM staining for the alpha3(IV) and alpha5(IV) collagen chains, whereas the epidermal basement membrane showed discontinuous alpha5(IV) collagen staining consistent with an X-linked carrier of AS. Few reports have shown discordance between kidney and skin biopsy findings as seen in this case, presumably due to X chromosome lyonization. We therefore suggest that simultaneous kidney and skin biopsies may be more accurate in the assessment of potential female carriers of AS than either kidney biopsy or skin biopsy alone.
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PMID:Discordance between skin biopsy and kidney biopsy in an X-linked carrier of Alport syndrome. 1729 21

Keratosis follicularis spinulosa decalvans is a rare, X-linked disorder of keratinization of the hair follicle with inflammation and atrophy associated with corneal dystrophy and other symptoms. A family with several affected members is reported. The unaffected parents were related. A 12-year-old girl and her 5-year-old brother had follicular spiny hyperkeratoses on the trunk and extremities. The girl had thinning of the eyelashes and eyebrows as well as scarring alopecia of the scalp as additional features of the disease. Both the girl and her brother had corneal dystrophy and photophobia. Two sisters aged 8 and 10 years did not show similar skin or eye findings.
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PMID:[Keratosis follicularis spinulosa decalvans]. 1755

Centronuclear myopathy (CNM) is an inherited neuromuscular disorder characterised by clinical features of a congenital myopathy and centrally placed nuclei on muscle biopsy.The incidence of X-linked myotubular myopathy is estimated at 2/100000 male births but epidemiological data for other forms are not currently available.The clinical picture is highly variable. The X-linked form usually gives rise to a severe phenotype in males presenting at birth with marked weakness and hypotonia, external ophthalmoplegia and respiratory failure. Signs of antenatal onset comprise reduced foetal movements, polyhydramnios and thinning of the ribs on chest radiographs; birth asphyxia may be the present. Affected infants are often macrosomic, with length above the 90th centile and large head circumference. Testes are frequently undescended. Both autosomal-recessive (AR) and autosomal-dominant (AD) forms differ from the X-linked form regarding age at onset, severity, clinical characteristics and prognosis. In general, AD forms have a later onset and milder course than the X-linked form, and the AR form is intermediate in both respects.Mutations in the myotubularin (MTM1) gene on chromosome Xq28 have been identified in the majority of patients with the X-linked recessive form, whilst AD and AR forms have been associated with mutations in the dynamin 2 (DNM2) gene on chromosome 19p13.2 and the amphiphysin 2 (BIN1) gene on chromosome 2q14, respectively. Single cases with features of CNM have been associated with mutations in the skeletal muscle ryanodine receptor (RYR1) and the hJUMPY (MTMR14) genes.Diagnosis is based on typical histopathological findings on muscle biopsy in combination with suggestive clinical features; muscle magnetic resonance imaging may complement clinical assessment and inform genetic testing in cases with equivocal features. Genetic counselling should be offered to all patients and families in whom a diagnosis of CNM has been made.The main differential diagnoses include congenital myotonic dystrophy and other conditions with severe neonatal hypotonia.Management of CNM is mainly supportive, based on a multidisciplinary approach. Whereas the X-linked form due to MTM1 mutations is often fatal in infancy, dominant forms due to DNM2 mutations and some cases of the recessive BIN1-related form appear to be associated with an overall more favourable prognosis.
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PMID:Centronuclear (myotubular) myopathy. 1881 72


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