1/27. Hereditary nephritis (with unusual renal histology): report of a first case from the west indies.A 21-year-old Grenadian girl undergoing investigation in Trinidad for anaemia was diagnosed as a case of hereditary nephritis. She had the clinical features of a nephropathy, nerve deafness and an ocular defect. Renal histology was exceptional in that in addition to the typical findings of a hereditary nephritis, cystic areas generally associated with medullary cystic disease were noted. Several members of the patient's maternal family were afflicted with either deafness visual distrubances or renal disease.- - - - - - - - - - ranking = 1keywords = member (Clic here for more details about this article) |
2/27. Autosomal recessive Alport syndrome: linkage analysis and clinical features in two families.BACKGROUND: genetic heterogeneity is a well-known feature of Alport syndrome (AS). Most families with AS show an X-linked dominant pattern of inheritance but about 15% of families show an autosomal inheritance of the disease. Autosomal recessive AS may account for 10% of the total number of cases and is caused by mutations in the COL4A3 and COL4A4 genes. The clinical spectrum of this rare disorder has not been well clarified. methods: We present two families with AS. Two affected members of these families have entered end-stage renal disease (ESRD) in their 30s, and the other three are older than 15 years and have normal serum creatinine. Four of the five patients have deafness but none have ocular abnormalities. Two have been transplanted and have not suffered from anti-GBM antibody nephritis. Men and women are equally affected. We have performed linkage analysis for chromosome 2 with the following markers: D2S279, COL4A3/4 DNTR, COL4A4 RFLP Hae III. RESULTS: We demonstrate that both families, one of them consanguineous, are linked to the COL4A3/4 locus. CONCLUSIONS: We can conclude that the only significant difference between the X-linked and the autosomal recessive forms of AS lies in the fact that in the latter females are as affected as males; thus the idea that autosomal recessive AS causes ESRD during childhood must be discarded. Other clinical features such as age of deafness or the presence of post-transplant anti-GBM antibody nephritis show no differences between the entities. Thus an accurate familial study is mandatory in patients with AS, as the identification of the different patterns of inheritance may cause a great difference in genetic counselling. Linkage analysis is the only effective molecular diagnosis that can be performed nowadays.- - - - - - - - - - ranking = 1keywords = member (Clic here for more details about this article) |
3/27. Hereditary nephritis, deafness and abnormal thrombopoiesis. Study of a new kindred.A fourth kindred displaying the triad of hereditary nephritis, deafness and thrombocytopenia with giant platelets is described. Renal involvement, a common cause of death amongst afflicted subjects, appears to have a better prognosis in the affected members of this family. Although the electron microscopic appearance of the megakaryocytes in the present case appears similar to that in previously reported cases, we suggest that the "giant" platelets may result from a degenerative process of megakaryocytes leading to nuclear regression and cytoplasmic fragmentation, rather than the usual blebbing process.- - - - - - - - - - ranking = 1keywords = member (Clic here for more details about this article) |
4/27. Coexistence of thin membrane and alport nephropathies in families with haematuria.The finding of familial haematuria without a history of deafness or renal impairment is often assumed to indicate a benign prognosis. However, we describe three families in whom Alport and thin basement membrane nephropathy were separately identified within the same pedigree. Our findings illustrate the importance of fully investigating families with haematuria, even if thin basement nephropathy has been diagnosed in one member.- - - - - - - - - - ranking = 1keywords = member (Clic here for more details about this article) |
5/27. Fechtner syndrome: physiologic analysis of macrothrombocytopenia.Fechtner syndrome is a rare autosomal dominant disorder consisting of macrothrombocytopenia and leukocyte inclusions, associated with Alport's syndrome (hereditary nephropathy, sensorineural hearing loss, and ocular anomalies). We describe a 71-year-old Caucasian male with a history of hearing loss and asymptomatic macrothrombocytopenia incidentally noted in 1985. Several challenges to hemostasis were uneventful, including total hip arthroplasty. He subsequently developed progressive renal failure, with 'nil lesions' by light and electron microscopy, which was responsive to corticosteroid therapy. Eight family members are affected variably by either thrombocytopenia or renal failure. Laboratory testing gave the following results: hemoglobin, 10.2 g/dl; leukocytes, 5.0 x 109/l; platelets, 64 x 109/l (mean platelet volume, 13.3 fl; normal platelet volume, 7.6-10.8 fl). Peripheral blood smear revealed thrombocytopenia and leukocytes with inclusions. Electron microscopy of the buffy coat confirmed Fechtner inclusions within the patient's leukocytes. Whole mount and thin section electron microscopy revealed a population of large, although not giant, platelets. Despite thrombocytopenia, platelet aggregation was normal. flow cytometry of dilute platelets revealed normal glycoprotein alphaII beta beta3 activation and alpha-granule p-selectin secretory response to 10 nmol/l human alpha-thrombin. Dense granule adenosine triphosphate secretory response to thrombin was likewise normal. This case illustrates that 'giant' platelets are not universally present in Fechtner syndrome cases, although the platelets are enlarged. Finally, renal pathology other than Alport's nephropathy may be associated with this syndrome.- - - - - - - - - - ranking = 6.6896192086141keywords = family member, member (Clic here for more details about this article) |
6/27. Familial interstitial nephritis with progressive renal failure.We describe a 53-year-old woman with chronic interstitial nephritis and asymptomatic impairment of renal function. Seven members of her family were suffering from renal failure and underwent hemodialysis. At the time of their hospital admissions, they had shown evidence of end-stage renal failure at 40 to 50 years of age. Lack of proteinuria, hematuria, hypertension, hyperuricemia, hearing loss, and visual impairment were present before the deterioration of the renal function. Renal biopsy of the presented case indicated chronic interstitial nephritis without glomerular basement membrane abnormalities. Progressive decline of renal function and the inheritance pattern of autosomal dominance in this family suggested the diagnosis of familial interstitial nephritis.- - - - - - - - - - ranking = 1keywords = member (Clic here for more details about this article) |
7/27. Approach to the diagnosis of thin basement membrane nephropathy in females with the use of antibodies to type IV collagen.CONTEXT: Thin basement membrane nephropathy is recognized by a diffusely thin glomerular basement membrane (GBM) ultrastructurally. In contrast to Alport syndrome (AS), there is no GBM thickening, lamellation, or granular inclusions. Morphologically, there is overlap between thin basement membrane nephropathy and AS in female patients in whom there might be only thin GBM and no pathognomonic findings of AS. OBJECTIVE: To determine if the use of antibodies to collagen IV is helpful in making the distinction between thin basement membrane nephropathy and AS in female patients with primarily thin GBMs. DESIGN: We examined renal biopsies from 9 adult female patients with thin GBMs for the presence of alpha1, alpha3, alpha4, and alpha5 chains of type IV collagen by immunofluorescence. RESULTS: In 2 patients with segmental GBM staining, no suggestion for AS was found on physical examination or in their family history. In the remaining 7 patients with normal GBM staining, 4 had family members with end-stage renal disease of unknown etiology, raising the suspicion of X-linked or autosomal-recessive AS. Three patients were presumed to have thin basement membrane nephropathy. CONCLUSION: Segmental GBM staining for alpha3, alpha4, and alpha5 chains of type IV collagen raises the suspicion of AS in the presence of adequate controls and other supporting evidence. Normal GBM staining for alpha3, alpha4, and alpha5 chains of type IV collagen, however, does not exclude AS.- - - - - - - - - - ranking = 6.6896192086141keywords = family member, member (Clic here for more details about this article) |
8/27. Autosomal dominant nephritis with renal failure of non-Alport type: clinical and molecular studies.BACKGROUND: Familial nephritis is a heterogeneous group of disorders caused by several genetic conditions such as Alport syndrome, glomerulonephritic syndromes, and unclassified nephritis without deafness or ocular defects. OBJECTIVES: To describe a family of Iraqi Jewish origin, several of whose members suffer from non-syndromic renal failure without deafness or ocular defects and where transmission is by autosomal dominant inheritance. We present the case histories of four family members and describe the molecular analysis performed in order to seek a possible linkage to one of the genes causing Alport or Alport-like syndromes. methods: We investigated all family members over the age of 18 for evidence of renal failure. We also extracted dna and carried out molecular linkage analysis with polymorphic markers in each of the known loci involved in Alport and Alport-like syndromes. RESULTS: histology of the renal biopsy specimens showed non-specific findings. Linkage was excluded for all the Alport and Alport-like syndrome loci. CONCLUSIONS: The condition suffered by several members of this family seems to represent a unique autosomal dominant type of progressive hereditary nephritis, characterized by hypertension and progressive renal failure without significant hematuria or proteinuria. The main histological changes are non-specific in the early stage of the disease. Our study rules out all the currently known genes that cause Alport syndrome as being responsible for the basic defect in this type of nephritis.- - - - - - - - - - ranking = 15.379238417228keywords = family member, member (Clic here for more details about this article) |
9/27. Complete amino acid sequence of the human alpha 5 (IV) collagen chain and identification of a single-base mutation in exon 23 converting glycine 521 in the collagenous domain to cysteine in an Alport syndrome patient.We have generated and characterized cDNA clones providing the complete amino acid sequence of the human type IV collagen chain whose gene has been shown to be mutated in x chromosome-linked Alport syndrome. The entire translation product has 1,685 amino acid residues. There is a 26-residue signal peptide, a 1,430-residue collagenous domain starting with a 14-residue noncollagenous sequence, and a Gly-Xaa-Yaa-repeat sequence interrupted at 22 locations, and a 229-residue carboxyl-terminal noncollagenous domain. The calculated molecular weight of the mature alpha 5(IV) chain is 158,303. Analysis of genomic dna from members of a kindred with Alport syndrome revealed a new HindIII cleavage site within the coding sequence of one of the cDNA clones characterized. The proband had a new 1.25-kilobase HindIII fragment and a lack of a 1.35-kilobase fragment, and his mildly affected female cousin had both alleles. The mutation which was located to exon 23 was sequenced from a polymerase chain reaction-amplified product, and shown to be a G T change in the coding strand. The mutation changed the GGT codon of glycine 521 to cysteine. The same mutation was found in one allele of the female cousin. The results were confirmed by allele-specific hybridization analyses.- - - - - - - - - - ranking = 1keywords = member (Clic here for more details about this article) |
10/27. Macrothrombocytopenia and progressive deafness: a new genetic syndrome.We report a kindred with hereditary macrothrombocytopenia and progressive sensorineural hearing loss. Although the occurrence of hereditary sensorineural hearing loss associated with macrothrombocytopenia has been reported in a small number of families, varying degrees of renal pathology have always been present. In contrast to the previously reported syndromes involving a giant-platelet disorder and deafness, none of the family members in this report have had any evidence of renal dysfunction. The disorder was inherited in a linear pattern from great-grandmother to grandmother to mother to daughter. The clinical manifestations include hearing impairment that begins before the third decade and progresses to severe to profound bilateral hearing loss by the fourth decade. The platelet disorder manifests in early childhood and persists lifelong, although it tends to remain subclinical. Hematologic and ultrastructural findings will be contrasted to those found in Alport syndrome.- - - - - - - - - - ranking = 6.6896192086141keywords = family member, member (Clic here for more details about this article) |
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