The Experts below are selected from a list of 33993 Experts worldwide ranked by ideXlab platform
Bernd Hoppe - One of the best experts on this subject based on the ideXlab platform.
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Evidence of true Genotype-Phenotype Correlation in primary hyperoxaluria type 1.
Kidney international, 2010Co-Authors: Bernd HoppeAbstract:A Genotype–Phenotype Correlation in patients with primary hyperoxaluria type 1 and specific AGXT mutations has supposedly been found, at least for sensitivity to medication and long-term outcome. Nevertheless, other determinants, such as environmental factors or modifier genes, must play an essential role in the intra- and interfamilial heterogeneity of this disease. Harambat and co-workers report on this situation, presenting data on a major population of Genotyped patients.
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Is there a Genotype-Phenotype Correlation in primary hyperoxaluria type 1?
Kidney international, 2006Co-Authors: Bodo B. Beck, Bernd HoppeAbstract:There is ongoing debate about a Genotype-Phenotype Correlation in patients with primary hyperoxaluria type 1 and specific AGXT mutations. However, other determinants like environmental factors or modifer genes may play a pivotal role in the heterogeneity of the disease. The report of Lorenzo and co-workers highlights this situation, presenting data of a whole population with just one specific AGXT mutation.
Friedhelm Hildebrandt - One of the best experts on this subject based on the ideXlab platform.
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Genotype Phenotype Correlation in 440 patients with nphp related ciliopathies
Kidney International, 2011Co-Authors: Moumita Chaki, Julia Hoefele, Edgar A Otto, Gokul Ramaswami, Susan J. Allen, Sabine Janssen, Carsten Bergmann, John R. Heckenlively, Friedhelm HildebrandtAbstract:Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, is the most frequent genetic cause for end-stage renal failure in the first three decades of life. Mutations in 13 genes ( NPHP1 - NPHP11 , AHI1 , and CC2D2A ) cause NPHP with ubiquitous expression of the corresponding proteins consistent with the multiorgan involvement of NPHP-related diseases. The Genotype–Phenotype Correlation in these ciliopathies can be explained by gene locus heterogeneity, allelism, and the impact of modifier genes. In some NPHP-related ciliopathies, the nature of the recessive mutations determines disease severity. In order to define the Genotype–Phenotype Correlation more clearly, we evaluated a worldwide cohort of 440 patients from 365 families with NPHP-related ciliopathies, in whom both disease-causing alleles were identified. The Phenotypes were ranked in the order of severity from degenerative to degenerative/dysplastic to dysplastic. A Genotype of two null alleles caused a range of Phenotypes, with an increasing order of severity of NPHP1 , NPHP3 , NPHP4 , NPHP5 , NPHP2 , NPHP10 , NPHP6 , to AHI1 . Only NPHP6 showed allelic influences on the Phenotypes; the presence of two null mutations caused dysplastic Phenotypes, whereas at least one missense allele rescued it to a milder degenerative Phenotype. We also found nine novel mutations in the NPHP genes. Thus, our studies have important implications for genetic counseling and planning of renal replacement therapy.
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Genotype–Phenotype Correlation in 440 patients with NPHP-related ciliopathies
Kidney international, 2011Co-Authors: Moumita Chaki, Julia Hoefele, Edgar A Otto, Gokul Ramaswami, Susan J. Allen, Sabine Janssen, Carsten Bergmann, John R. Heckenlively, Friedhelm HildebrandtAbstract:Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, is the most frequent genetic cause for end-stage renal failure in the first three decades of life. Mutations in 13 genes ( NPHP1 - NPHP11 , AHI1 , and CC2D2A ) cause NPHP with ubiquitous expression of the corresponding proteins consistent with the multiorgan involvement of NPHP-related diseases. The Genotype–Phenotype Correlation in these ciliopathies can be explained by gene locus heterogeneity, allelism, and the impact of modifier genes. In some NPHP-related ciliopathies, the nature of the recessive mutations determines disease severity. In order to define the Genotype–Phenotype Correlation more clearly, we evaluated a worldwide cohort of 440 patients from 365 families with NPHP-related ciliopathies, in whom both disease-causing alleles were identified. The Phenotypes were ranked in the order of severity from degenerative to degenerative/dysplastic to dysplastic. A Genotype of two null alleles caused a range of Phenotypes, with an increasing order of severity of NPHP1 , NPHP3 , NPHP4 , NPHP5 , NPHP2 , NPHP10 , NPHP6 , to AHI1 . Only NPHP6 showed allelic influences on the Phenotypes; the presence of two null mutations caused dysplastic Phenotypes, whereas at least one missense allele rescued it to a milder degenerative Phenotype. We also found nine novel mutations in the NPHP genes. Thus, our studies have important implications for genetic counseling and planning of renal replacement therapy.
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Genotype Phenotype Correlation in nephrotic syndrome caused by wt1 mutations
Clinical Journal of The American Society of Nephrology, 2010Co-Authors: Gil Chernin, Friedhelm Hildebrandt, Fatih Ozaltin, Virginia Vegawarner, Dominik S Schoeb, Saskia F Heeringa, Bugsu Ovunc, Pawaree Saisawat, Roxana CleperAbstract:Background and objectives: The risk of developing Wilms tumor (WT) can be present or absent in patients with nephrotic syndrome (NS) caused by WT1 mutations. Here, the Genotype/Phenotype Correlation regarding the outcome and risk for WT in 52 patients from 51 families with NS due to WT1 mutations is described. Design, setting, participants, & measurements: This study followed 19 patients with mutations in intron 9 splice donor site (KTS mutations), 27 patients with missense mutations, 4 patients with nonsense mutations, 1 patient with a splice site mutation in intron 8, and 1 patient with a deletion. Results: Twenty-four different WT1 mutations were detected. Sixteen of the 19 patients with KTS mutations were females. These patients had isolated NS if karyotype was 46,XX and Frasier syndrome if karyotype was 46,XY. Patients with KTS mutations presented at a significantly older age and with a slower progression toward chronic kidney disease (CKD) stage 5, compared with missense mutations. Patients with nonsense mutations presented initially with WT. Six patients with missense mutations developed WT after the diagnosis of NS (interval-range from NS onset to WT of 0.1 to 1.4 years). Conclusions: ( 1 ) KTS mutations cause isolated NS with absence of WT in 46,XX females. ( 2 ) KTS mutations cause Frasier syndrome with gonadoblastoma risk in 46,XY phenotypic females. ( 3 ) KTS mutations cause NS with a slower progression when compared with missense mutations. ( 4 ) Missense mutations can occur with and without WT. ( 5 ) WT1 analysis is important in young patients with NS for early detection and tumor prophylaxis.
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Genotype/Phenotype Correlation in Nephrotic Syndrome Caused by WT1 Mutations
Clinical journal of the American Society of Nephrology : CJASN, 2010Co-Authors: Gil Chernin, Fatih Ozaltin, Dominik S Schoeb, Saskia F Heeringa, Bugsu Ovunc, Pawaree Saisawat, Roxana Cleper, Virginia Vega-warner, Friedhelm HildebrandtAbstract:Background and objectives: The risk of developing Wilms tumor (WT) can be present or absent in patients with nephrotic syndrome (NS) caused by WT1 mutations. Here, the Genotype/Phenotype Correlation regarding the outcome and risk for WT in 52 patients from 51 families with NS due to WT1 mutations is described. Design, setting, participants, & measurements: This study followed 19 patients with mutations in intron 9 splice donor site (KTS mutations), 27 patients with missense mutations, 4 patients with nonsense mutations, 1 patient with a splice site mutation in intron 8, and 1 patient with a deletion. Results: Twenty-four different WT1 mutations were detected. Sixteen of the 19 patients with KTS mutations were females. These patients had isolated NS if karyotype was 46,XX and Frasier syndrome if karyotype was 46,XY. Patients with KTS mutations presented at a significantly older age and with a slower progression toward chronic kidney disease (CKD) stage 5, compared with missense mutations. Patients with nonsense mutations presented initially with WT. Six patients with missense mutations developed WT after the diagnosis of NS (interval-range from NS onset to WT of 0.1 to 1.4 years). Conclusions: ( 1 ) KTS mutations cause isolated NS with absence of WT in 46,XX females. ( 2 ) KTS mutations cause Frasier syndrome with gonadoblastoma risk in 46,XY phenotypic females. ( 3 ) KTS mutations cause NS with a slower progression when compared with missense mutations. ( 4 ) Missense mutations can occur with and without WT. ( 5 ) WT1 analysis is important in young patients with NS for early detection and tumor prophylaxis.
Michele Callea - One of the best experts on this subject based on the ideXlab platform.
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5-α-Reductase type 2 deficiency: is there a Genotype-Phenotype Correlation? A review
Hormones, 2018Co-Authors: Andrea Avendaño, Irene Paradisi, Francisco Cammarata-scalisi, Michele CalleaAbstract:5-α-Reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, a potent androgen responsible for male sexual development during the fetal period and later during puberty. Its deficiency causes an autosomal recessive disorder of sex development characterized by a wide range of under-virilization of external genitalia in patients with a 46,XY karyotype. Mutations in the SRD5A2 gene cause 5-α-Reductase deficiency; although it is an infrequent disorder, it has been reported worldwide, with mutational heterogeneity. Furthermore, it has been proposed that there is no Genotype-Phenotype Correlation, even in patients carrying the same mutation. The aim of this review was to perform an extensive search in various databases and to select those articles with a comprehensive Genotype and Phenotype description of the patients, classifying their Phenotypes using the external masculinization score (EMS). Thus, it was possible to objectively compare the eventual Genotype-Phenotype Correlation between them. The analysis showed that for most of the studied mutations no Correlation can be established, although the specific location of the mutation in the protein has an effect on the severity of the Phenotype. Nevertheless, even in patients carrying the same homozygous mutation, a variable Phenotype was observed, suggesting that additional genetic factors might be influencing it. Due to the clinical variability of the disorder, an accurate diagnosis and adequate medical management might be difficult to carry out, as is highlighted in the review.
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5-α-Reductase type 2 deficiency: is there a Genotype-Phenotype Correlation? A review
Hormones, 2018Co-Authors: Andrea Avendaño, Irene Paradisi, Francisco Cammarata-scalisi, Michele CalleaAbstract:5-α-Reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, a potent androgen responsible for male sexual development during the fetal period and later during puberty. Its deficiency causes an autosomal recessive disorder of sex development characterized by a wide range of under-virilization of external genitalia in patients with a 46,XY karyotype. Mutations in the SRD5A2 gene cause 5-α-Reductase deficiency; although it is an infrequent disorder, it has been reported worldwide, with mutational heterogeneity. Furthermore, it has been proposed that there is no Genotype-Phenotype Correlation, even in patients carrying the same mutation. The aim of this review was to perform an extensive search in various databases and to select those articles with a comprehensive Genotype and Phenotype description of the patients, classifying their Phenotypes using the external masculinization score (EMS). Thus, it was possible to objectively compare the eventual Genotype-Phenotype Correlation between them. The analysis showed that for most of the studied mutations no Correlation can be established, although the specific location of the mutation in the protein has an effect on the severity of the Phenotype. Nevertheless, even in patients carrying the same homozygous mutation, a variable Phenotype was observed, suggesting that additional genetic factors might be influencing it. Due to the clinical variability of the disorder, an accurate diagnosis and adequate medical management might be difficult to carry out, as is highlighted in the review.
André Reis - One of the best experts on this subject based on the ideXlab platform.
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Genotype Phenotype Correlation in autosomal recessive lamellar ichthyosis
American Journal of Human Genetics, 1998Co-Authors: Hans Christian Hennies, Wolfgang Küster, Victor Wiebe, Alice Krebsová, André ReisAbstract:Autosomal recessive lamellar ichthyosis is a severe congenital disorder of keratinization, characterized by variable erythema of the whole body surface and by different scaling patterns. Recently, mutations have been identified in patients with lamellar ichthyosis in the TGM1 gene coding for keratinocyte transglutaminase, and a second locus has been mapped to chromosome 2. We have now analyzed the Genotype/Phenotype Correlation in a total of 14 families with lamellar ichthyosis. Linkage analyses using microsatellites in the region of the TGM1 gene confirmed genetic heterogeneity. In patients not linked to the TGM1 gene, the second region identified on chromosome 2 and a further candidate region on chromosome 20 were excluded, confirming as well the existence of at least three loci for lamellar ichthyosis. Sequence analyses of the TGM1 gene in families compatible with linkage to this locus revealed seven different missense mutations, five of these unpublished so far, and one splice mutation. No Genotype/Phenotype Correlation for mutations in the TGM1 gene was found in this group of patients, which included two unrelated patients homozygous for the same mutation. Similarly, no clear difference in the clinical picture was seen between patients with TGM1 mutations and those unlinked to the TGM1 locus. Comparison of genetic and clinical classifications for patients with lamellar ichthyosis shows no consistency and thus indicates that clinical criteria currently in use cannot discriminate between the molecularly different forms of the disease.
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Genotype/Phenotype Correlation in Autosomal Recessive Lamellar Ichthyosis
American journal of human genetics, 1998Co-Authors: Hans Christian Hennies, Wolfgang Küster, Victor Wiebe, Alice Krebsová, André ReisAbstract:Autosomal recessive lamellar ichthyosis is a severe congenital disorder of keratinization, characterized by variable erythema of the whole body surface and by different scaling patterns. Recently, mutations have been identified in patients with lamellar ichthyosis in the TGM1 gene coding for keratinocyte transglutaminase, and a second locus has been mapped to chromosome 2. We have now analyzed the Genotype/Phenotype Correlation in a total of 14 families with lamellar ichthyosis. Linkage analyses using microsatellites in the region of the TGM1 gene confirmed genetic heterogeneity. In patients not linked to the TGM1 gene, the second region identified on chromosome 2 and a further candidate region on chromosome 20 were excluded, confirming as well the existence of at least three loci for lamellar ichthyosis. Sequence analyses of the TGM1 gene in families compatible with linkage to this locus revealed seven different missense mutations, five of these unpublished so far, and one splice mutation. No Genotype/Phenotype Correlation for mutations in the TGM1 gene was found in this group of patients, which included two unrelated patients homozygous for the same mutation. Similarly, no clear difference in the clinical picture was seen between patients with TGM1 mutations and those unlinked to the TGM1 locus. Comparison of genetic and clinical classifications for patients with lamellar ichthyosis shows no consistency and thus indicates that clinical criteria currently in use cannot discriminate between the molecularly different forms of the disease.
Rami A. Jarjour - One of the best experts on this subject based on the ideXlab platform.
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Familial Mediterranean fever in Syrian patients: MEFV gene mutations and Genotype–Phenotype Correlation
Molecular Biology Reports, 2010Co-Authors: Rami A. JarjourAbstract:Familial Mediterranean fever is an autosomal recessive disorder characterized by recurrent attacks of abdominal pain, synovitis and pleuritis. MEFV gene mutations are responsible for the disease. The objective of this study was to identify the frequency and distribution of 12 MEFV mutations in 153 Syrian patients and perform a Genotype–Phenotype Correlation in the patients’ cohort. Of the 153 unrelated patients investigated, 97 (63.4%) had at least one mutation. The most frequent mutation was M694V (36.5%), followed by V726A (15.2%), E148Q (14.5%), M680I (G/C) (13.2%), and M694I (10.2%) mutations. Rare mutations (R761H, A744S, M680I (G/A), K695R, P369S, F479L and I692del) were also detected in the patients. M694V was associated with the severe form of the disease. The identification of a significant number of FMF patients with no mutations or only one known mutation identified indicates the presence of new mutations in the MEFV gene which will be investigated in the future.
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familial mediterranean fever in syrian patients mefv gene mutations and Genotype Phenotype Correlation
Molecular Biology Reports, 2010Co-Authors: Rami A. JarjourAbstract:Familial Mediterranean fever is an autosomal recessive disorder characterized by recurrent attacks of abdominal pain, synovitis and pleuritis. MEFV gene mutations are responsible for the disease. The objective of this study was to identify the frequency and distribution of 12 MEFV mutations in 153 Syrian patients and perform a Genotype–Phenotype Correlation in the patients’ cohort. Of the 153 unrelated patients investigated, 97 (63.4%) had at least one mutation. The most frequent mutation was M694V (36.5%), followed by V726A (15.2%), E148Q (14.5%), M680I (G/C) (13.2%), and M694I (10.2%) mutations. Rare mutations (R761H, A744S, M680I (G/A), K695R, P369S, F479L and I692del) were also detected in the patients. M694V was associated with the severe form of the disease. The identification of a significant number of FMF patients with no mutations or only one known mutation identified indicates the presence of new mutations in the MEFV gene which will be investigated in the future.