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Ken Mcelreavey - One of the best experts on this subject based on the ideXlab platform.
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pathogenic variants in the deah box rna helicase dhx37 are a frequent cause of 46 xy Gonadal Dysgenesis and 46 xy testicular regression syndrome
Genetics in Medicine, 2020Co-Authors: Ken Mcelreavey, Joelle Bignontopalovic, Anne Jorgensen, Caroline Eozenou, Tiphanie Merel, Daisylyn Senna Tan, Denis Houzelstein, Federica Buonocore, Nick Warr, Raissa KayAbstract:XY individuals with disorders/differences of sex development (DSD) are characterized by reduced androgenization caused, in some children, by Gonadal Dysgenesis or testis regression during fetal development. The genetic etiology for most patients with 46,XY Gonadal Dysgenesis and for all patients with testicular regression syndrome (TRS) is unknown. We performed exome and/or Sanger sequencing in 145 individuals with 46,XY DSD of unknown etiology including Gonadal Dysgenesis and TRS. Thirteen children carried heterozygous missense pathogenic variants involving the RNA helicase DHX37, which is essential for ribosome biogenesis. Enrichment of rare/novel DHX37 missense variants in 46,XY DSD is highly significant compared with controls (P value = 5.8 × 10−10). Five variants are de novo (P value = 1.5 × 10−5). Twelve variants are clustered in two highly conserved functional domains and were specifically associated with Gonadal Dysgenesis and TRS. Consistent with a role in early testis development, DHX37 is expressed specifically in somatic cells of the developing human and mouse testis. DHX37 pathogenic variants are a new cause of an autosomal dominant form of 46,XY DSD, including Gonadal Dysgenesis and TRS, showing that these conditions are part of a clinical spectrum. This raises the possibility that some forms of DSD may be a ribosomopathy.
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early recognition of Gonadal Dysgenesis in congenital nephrotic syndrome
Clinical Nephrology, 2016Co-Authors: Supamit Ukarapong, Ken Mcelreavey, Anu Bashamboo, Gary D Berkovitz, Yong BaoAbstract:Mutation of the Wilms tumor suppressor gene (WT1) has been recognized as one of the etiologies of steroid-resistant nephrotic syndrome (SRNS). The mutation is also responsible for Gonadal Dysgenesis in 46,XY individuals. Early recognition of the presence of Y chromosome is of particular importance because of the high risk of Gonadal tumor. We present here three cases of steroid-resistant nephrotic syndrome with WT1 mutation and 46,XY karyotype. Patient 1 and 2 have intron splice site (IVS9+5G A) mutation. Patient 3 has c.1301GA (p. R434H) mutation. All cases had normal female external genitalia at birth and eluded the diagnosis of Gonadal Dysgenesis until later in life. We suggest that chromosomal analysis should be promptly performed in female patients with early-onset steroid-resistant nephrotic syndrome. .
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identification of nr5a1 mutations and possible digenic inheritance in 46 xy Gonadal Dysgenesis
Sexual Development, 2016Co-Authors: Inas Mazen, Mohamed S Abdelhamid, Mona K Mekkawy, Joelle Bignontopalovic, Radia Boudjenah, Mona El Gammal, Mona L Essawi, Anu Bashamboo, Ken McelreaveyAbstract:The phenotypic spectrum of patients carrying NR5A1 mutations ranges from 46,XY Gonadal Dysgenesis to male infertility. Phenotypic variability could be due to digenic or oligogenic inheritance of pathogenic variants in other testis-determining genes. Here, exome sequencing identified 2 pathogenic de novo NR5A1 mutations in 2 patients with 46,XY Gonadal Dysgenesis, p.Q206Tfs*20 and p.Arg313Cys. The latter patient also carried a missense mutation in MAP3K1. Our data extend the number of NR5A1 gene mutations associated with Gonadal Dysgenesis. The combination of an NR5A1 mutation with a MAP3K1 variant may explain the phenotypic variability associated with NR5A1 mutations.
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mapping a gene for 46 xy Gonadal Dysgenesis by linkage analysis
Clinical Genetics, 2003Co-Authors: D Jawaheer, S H H Juo, Le C Caignec, Albert David, Christine Petit, Peter K Gregersen, S Dowbak, Aarti Damle, Ken Mcelreavey, Harry OstrerAbstract:46,XY Gonadal Dysgenesis was transmitted as an autosomal-dominant trait in a large family with multiple affected members. Expressivity of the trait was highly variable, ranging from pure to partial Gonadal Dysgenesis associated with normal female genitalia or sexual ambiguity, to mild hypospadias in otherwise normal males. The phenotypic features of this trait appeared to be confined to the genitourinary system. Multipoint parametric analysis using markers D5S664, D5S633, and D5D2102 yielded an LOD score of 4.47, assuming sex-limited, autosomal-dominant inheritance with a penetrance of 0.6. Because mutation in testis-determining genes leads to Gonadal Dysgenesis in 46,XY individuals, we postulate that the gene mapped by this study normally plays a role in Gonadal differentiation.
Raissa Kay - One of the best experts on this subject based on the ideXlab platform.
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pathogenic variants in the deah box rna helicase dhx37 are a frequent cause of 46 xy Gonadal Dysgenesis and 46 xy testicular regression syndrome
Genetics in Medicine, 2020Co-Authors: Ken Mcelreavey, Joelle Bignontopalovic, Anne Jorgensen, Caroline Eozenou, Tiphanie Merel, Daisylyn Senna Tan, Denis Houzelstein, Federica Buonocore, Nick Warr, Raissa KayAbstract:XY individuals with disorders/differences of sex development (DSD) are characterized by reduced androgenization caused, in some children, by Gonadal Dysgenesis or testis regression during fetal development. The genetic etiology for most patients with 46,XY Gonadal Dysgenesis and for all patients with testicular regression syndrome (TRS) is unknown. We performed exome and/or Sanger sequencing in 145 individuals with 46,XY DSD of unknown etiology including Gonadal Dysgenesis and TRS. Thirteen children carried heterozygous missense pathogenic variants involving the RNA helicase DHX37, which is essential for ribosome biogenesis. Enrichment of rare/novel DHX37 missense variants in 46,XY DSD is highly significant compared with controls (P value = 5.8 × 10−10). Five variants are de novo (P value = 1.5 × 10−5). Twelve variants are clustered in two highly conserved functional domains and were specifically associated with Gonadal Dysgenesis and TRS. Consistent with a role in early testis development, DHX37 is expressed specifically in somatic cells of the developing human and mouse testis. DHX37 pathogenic variants are a new cause of an autosomal dominant form of 46,XY DSD, including Gonadal Dysgenesis and TRS, showing that these conditions are part of a clinical spectrum. This raises the possibility that some forms of DSD may be a ribosomopathy.
Enhua Wang - One of the best experts on this subject based on the ideXlab platform.
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dysgerminoma in a case of 46 xy pure Gonadal Dysgenesis swyer syndrome a case report
Diagnostic Pathology, 2011Co-Authors: Yanyan Wang, Qingchang Li, Anguang He, Enhua WangAbstract:Simple 46, XY Gonadal Dysgenesis syndrome, also called Swyer syndrome, is known as pure Gonadal Dysgenesis. Individuals with the syndrome are characterized by 46, XY karyotype and phenotypically female with female genital appearance, normal Mullerian structures and absent testicular tissue. The condition usually first becomes apparent in adolescence with delayed puberty and primary amenorrhea due to the gonads have no hormonal or reproductive potential. Herein, we report a case of dysgerminoma diagnosed in a dysgenetic gonad of a 21-year-old patient with Swyer syndrome.
Kenneth I Glassberg - One of the best experts on this subject based on the ideXlab platform.
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mixed Gonadal Dysgenesis and dysgenetic male pseudohermaphroditism
The Journal of Urology, 1995Co-Authors: Joseph G Borer, Victor W Nitti, Kenneth I GlassbergAbstract:AbstractMixed Gonadal Dysgenesis and dysgenetic male pseudohermaphroditism are 2 forms of male pseudohermaphroditism that present with absent mullerian regression and ambiguous genitalia. We present a retrospective analysis of 10 patients with the diagnosis of either mixed Gonadal Dysgenesis or dysgenetic male pseudohermaphroditism encountered during a 16-year period at our institution. We assigned a female gender to 4 patients and a male gender to 3. Three patients were assigned a male gender before referral (2 for whom we would have preferred female assignment). All intra-abdominal gonads were removed except in 2 patients assigned a male gender who underwent bilateral orchiopexy. Patients underwent hypospadias repair or feminizing genitoplasty depending upon the gender assigned. Although female gender assignment is usually preferred, male assignment is a justifiable alternative in instances of extreme virilization and a descended testis. However, in these male assigned patients, consideration must be gi...
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Mixed Gonadal Dysgenesis and dysgenetic male pseudohermaphroditism.
The Journal of urology, 1995Co-Authors: Joseph G Borer, Victor W Nitti, Kenneth I GlassbergAbstract:Mixed Gonadal Dysgenesis and dysgenetic male pseudohermaphroditism are 2 forms of male pseudohermaphroditism that present with absent mullerian regression and ambiguous genitalia. We present a retrospective analysis of 10 patients with the diagnosis of either mixed Gonadal Dysgenesis or dysgenetic male pseudohermaphroditism encountered during a 16-year period at our institution. We assigned a female gender to 4 patients and a male gender to 3. Three patients were assigned a male gender before referral (2 for whom we would have preferred female assignment). All intra-abdominal gonads were removed except in 2 patients assigned a male gender who underwent bilateral orchiopexy. Patients underwent hypospadias repair or feminizing genitoplasty depending upon the gender assigned. Although female gender assignment is usually preferred, male assignment is a justifiable alternative in instances of extreme virilization and a descended testis. However, in these male assigned patients, consideration must be given to the role of periodic testicular biopsies. In light of tumor potential, all intra-abdominal gonads should be removed. When necessary, appropriate surgical genitoplasty should be performed at an early patient age.
Joelle Bignontopalovic - One of the best experts on this subject based on the ideXlab platform.
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pathogenic variants in the deah box rna helicase dhx37 are a frequent cause of 46 xy Gonadal Dysgenesis and 46 xy testicular regression syndrome
Genetics in Medicine, 2020Co-Authors: Ken Mcelreavey, Joelle Bignontopalovic, Anne Jorgensen, Caroline Eozenou, Tiphanie Merel, Daisylyn Senna Tan, Denis Houzelstein, Federica Buonocore, Nick Warr, Raissa KayAbstract:XY individuals with disorders/differences of sex development (DSD) are characterized by reduced androgenization caused, in some children, by Gonadal Dysgenesis or testis regression during fetal development. The genetic etiology for most patients with 46,XY Gonadal Dysgenesis and for all patients with testicular regression syndrome (TRS) is unknown. We performed exome and/or Sanger sequencing in 145 individuals with 46,XY DSD of unknown etiology including Gonadal Dysgenesis and TRS. Thirteen children carried heterozygous missense pathogenic variants involving the RNA helicase DHX37, which is essential for ribosome biogenesis. Enrichment of rare/novel DHX37 missense variants in 46,XY DSD is highly significant compared with controls (P value = 5.8 × 10−10). Five variants are de novo (P value = 1.5 × 10−5). Twelve variants are clustered in two highly conserved functional domains and were specifically associated with Gonadal Dysgenesis and TRS. Consistent with a role in early testis development, DHX37 is expressed specifically in somatic cells of the developing human and mouse testis. DHX37 pathogenic variants are a new cause of an autosomal dominant form of 46,XY DSD, including Gonadal Dysgenesis and TRS, showing that these conditions are part of a clinical spectrum. This raises the possibility that some forms of DSD may be a ribosomopathy.
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identification of nr5a1 mutations and possible digenic inheritance in 46 xy Gonadal Dysgenesis
Sexual Development, 2016Co-Authors: Inas Mazen, Mohamed S Abdelhamid, Mona K Mekkawy, Joelle Bignontopalovic, Radia Boudjenah, Mona El Gammal, Mona L Essawi, Anu Bashamboo, Ken McelreaveyAbstract:The phenotypic spectrum of patients carrying NR5A1 mutations ranges from 46,XY Gonadal Dysgenesis to male infertility. Phenotypic variability could be due to digenic or oligogenic inheritance of pathogenic variants in other testis-determining genes. Here, exome sequencing identified 2 pathogenic de novo NR5A1 mutations in 2 patients with 46,XY Gonadal Dysgenesis, p.Q206Tfs*20 and p.Arg313Cys. The latter patient also carried a missense mutation in MAP3K1. Our data extend the number of NR5A1 gene mutations associated with Gonadal Dysgenesis. The combination of an NR5A1 mutation with a MAP3K1 variant may explain the phenotypic variability associated with NR5A1 mutations.