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Velibor Tasic - One of the best experts on this subject based on the ideXlab platform.
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duplication of the sox3 gene in an sry negative 46 xx male with associated congenital anomalies of Kidneys and the urinary tract case report and review of the literature
Balkan Journal of Medical Genetics, 2019Co-Authors: Velibor Tasic, Adele Mitrotti, F Riepe, A E Kulle, Nevenka Laban, Momir Polenakovic, Dijana Plaseskakaranfilska, Simone Sannacherchi, M Kostovski, Zoran GucevAbstract:Disorders of sex development (DSD) are a group of rare conditions characterized by discrepancy between chromosomal sex, gonads and external genitalia. Congenital abnormalities of the Kidney and urinary tract are often associated with DSD, mostly in multiple malformation syndromes. We describe the case of an 11-year-old Caucasian boy, with right Kidney Hypoplasia and hypospadias. Genome-wide copy number variation (CNV) analysis revealed a unique duplication of about 550 kb on chromosome Xq27, and a 46,XX karyotype, consistent with a sex reversal phenotype. This region includes multiple genes, and, among these, SOX3 emerged as the main phenotypic driver. This is the fifth case reporting a genomic imbalance involving the SOX3 gene in a 46,XX SRY-negative male, and the first with associated renal malformations. Our data provide plausible links between SOX3 gene dosage and Kidney malformations. It is noteworthy that the current and reported SOX3 gene duplications are below the detection threshold of standard karyotypes and were found only by analyzing CNVs using DNA microarrays. Therefore, all 46,XX SRY-negative males should be screened for SOX3 gene duplications with DNA microarrays.
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Presentation1.PDF
2018Co-Authors: Aleksandra Stajkovska, Velibor Tasic, Sanja Mehandziska, Margarita Stavrevska, Kristina Jakovleva, Natasha Nikchevska, Zan Mitrev, Ivan Kungulovski, Gjorgje Zafiroski, Goran KungulovskiAbstract:Exome sequencing can interrogate thousands of genes simultaneously and it is becoming a first line diagnostic tool in genomic medicine. Herein, we applied trio clinical exome sequencing (CES) in a patient presenting with undiagnosed skeletal disorder, minor facial abnormalities, and Kidney Hypoplasia; her parents were asymptomatic. Testing the proband and her parents led to the identification of a de novo mutation c.188C>T (p.Pro63Leu) in the MAFB gene, which is known to cause multicentric carpotarsal osteolysis syndrome (MCTO). The c.188C>T mutation lies in a hotspot amino acid stretch within the transactivation domain of MAFB, which is a negative regulator of RANKL-induced osteoclastogenesis. MCTO is an extremely rare autosomal dominant (AD) disorder that typically arises spontaneously and causes carpotarsal osteolysis, often followed by nephropathy. To the best of our knowledge, this is the first study reporting genetically diagnosed MCTO in the Balkans.
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Trio Clinical Exome Sequencing in a Patient With Multicentric Carpotarsal Osteolysis Syndrome: First Case Report in the Balkans
Frontiers Media S.A., 2018Co-Authors: Aleksandra Stajkovska, Velibor Tasic, Sanja Mehandziska, Margarita Stavrevska, Kristina Jakovleva, Natasha Nikchevska, Zan Mitrev, Ivan Kungulovski, Gjorgje Zafiroski, Goran KungulovskiAbstract:Exome sequencing can interrogate thousands of genes simultaneously and it is becoming a first line diagnostic tool in genomic medicine. Herein, we applied trio clinical exome sequencing (CES) in a patient presenting with undiagnosed skeletal disorder, minor facial abnormalities, and Kidney Hypoplasia; her parents were asymptomatic. Testing the proband and her parents led to the identification of a de novo mutation c.188C>T (p.Pro63Leu) in the MAFB gene, which is known to cause multicentric carpotarsal osteolysis syndrome (MCTO). The c.188C>T mutation lies in a hotspot amino acid stretch within the transactivation domain of MAFB, which is a negative regulator of RANKL-induced osteoclastogenesis. MCTO is an extremely rare autosomal dominant (AD) disorder that typically arises spontaneously and causes carpotarsal osteolysis, often followed by nephropathy. To the best of our knowledge, this is the first study reporting genetically diagnosed MCTO in the Balkans
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740 Duplication of the Sox3 Gene in a Sry Negative 46, XX Male
Archives of Disease in Childhood, 2012Co-Authors: Zoran Gucev, Ali G. Gharavi, Simone Sanna-cherchi, Felix G. Riepe, Velibor TasicAbstract:Case presentation An 11 old patient with Hypoplasia of the right Kidney and hypospadias was found to be SRY negative, 46, XX. His parents and younger sister were healthy. His intelligence was normal (IQ 92) and he had no other anomalies. The behavior, growth and development were all normal. His testes were >4ml and the penis was 5 cm. Ultrasound and MRI did not show internal female genitals, while confirming right Kidney Hypoplasia (as did the DMSA scan). ACTH test showed normal basal and stimulated 17OH-progesterone excluding a form of 46XX DSD due to 21-hydroxylase deficiency. 11-DOC and 11S were normal at both baseline and after ACTH stimulation, excluding 11-hydroxylase deficiency. Cortisol levels were in the mid normal range at baseline and responded to stimulation, excluding primary adrenal insufficiency. Androstenedione, The hCG test found testosterone in the low normal range for male sex and age at baseline. It rised up to 146 ng/mL indicating the presence of functional Leydig cells targeted by hCG. The stimulated ratio T:DHT was 5.6, not supporting 5 alpha-reductase deficiency. SNP array for copy number variations (CNV’s) showed a unique 550 kb duplication involving SOX3, RP1–177G6, and CDR1 genes, and the microRNA MIR320D2. This CNV was absent in 13,839 controls. Conclusions A SRY negative 46, XX male with renal hypodysplasia was found to have an exceedingly rare duplication involving the SOX-3 gene, proving its role in sex determination and suggesting its evolvement in Kidney development.
Zoran Gucev - One of the best experts on this subject based on the ideXlab platform.
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duplication of the sox3 gene in an sry negative 46 xx male with associated congenital anomalies of Kidneys and the urinary tract case report and review of the literature
Balkan Journal of Medical Genetics, 2019Co-Authors: Velibor Tasic, Adele Mitrotti, F Riepe, A E Kulle, Nevenka Laban, Momir Polenakovic, Dijana Plaseskakaranfilska, Simone Sannacherchi, M Kostovski, Zoran GucevAbstract:Disorders of sex development (DSD) are a group of rare conditions characterized by discrepancy between chromosomal sex, gonads and external genitalia. Congenital abnormalities of the Kidney and urinary tract are often associated with DSD, mostly in multiple malformation syndromes. We describe the case of an 11-year-old Caucasian boy, with right Kidney Hypoplasia and hypospadias. Genome-wide copy number variation (CNV) analysis revealed a unique duplication of about 550 kb on chromosome Xq27, and a 46,XX karyotype, consistent with a sex reversal phenotype. This region includes multiple genes, and, among these, SOX3 emerged as the main phenotypic driver. This is the fifth case reporting a genomic imbalance involving the SOX3 gene in a 46,XX SRY-negative male, and the first with associated renal malformations. Our data provide plausible links between SOX3 gene dosage and Kidney malformations. It is noteworthy that the current and reported SOX3 gene duplications are below the detection threshold of standard karyotypes and were found only by analyzing CNVs using DNA microarrays. Therefore, all 46,XX SRY-negative males should be screened for SOX3 gene duplications with DNA microarrays.
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740 Duplication of the Sox3 Gene in a Sry Negative 46, XX Male
Archives of Disease in Childhood, 2012Co-Authors: Zoran Gucev, Ali G. Gharavi, Simone Sanna-cherchi, Felix G. Riepe, Velibor TasicAbstract:Case presentation An 11 old patient with Hypoplasia of the right Kidney and hypospadias was found to be SRY negative, 46, XX. His parents and younger sister were healthy. His intelligence was normal (IQ 92) and he had no other anomalies. The behavior, growth and development were all normal. His testes were >4ml and the penis was 5 cm. Ultrasound and MRI did not show internal female genitals, while confirming right Kidney Hypoplasia (as did the DMSA scan). ACTH test showed normal basal and stimulated 17OH-progesterone excluding a form of 46XX DSD due to 21-hydroxylase deficiency. 11-DOC and 11S were normal at both baseline and after ACTH stimulation, excluding 11-hydroxylase deficiency. Cortisol levels were in the mid normal range at baseline and responded to stimulation, excluding primary adrenal insufficiency. Androstenedione, The hCG test found testosterone in the low normal range for male sex and age at baseline. It rised up to 146 ng/mL indicating the presence of functional Leydig cells targeted by hCG. The stimulated ratio T:DHT was 5.6, not supporting 5 alpha-reductase deficiency. SNP array for copy number variations (CNV’s) showed a unique 550 kb duplication involving SOX3, RP1–177G6, and CDR1 genes, and the microRNA MIR320D2. This CNV was absent in 13,839 controls. Conclusions A SRY negative 46, XX male with renal hypodysplasia was found to have an exceedingly rare duplication involving the SOX-3 gene, proving its role in sex determination and suggesting its evolvement in Kidney development.
Felix G. Riepe - One of the best experts on this subject based on the ideXlab platform.
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740 Duplication of the Sox3 Gene in a Sry Negative 46, XX Male
Archives of Disease in Childhood, 2012Co-Authors: Zoran Gucev, Ali G. Gharavi, Simone Sanna-cherchi, Felix G. Riepe, Velibor TasicAbstract:Case presentation An 11 old patient with Hypoplasia of the right Kidney and hypospadias was found to be SRY negative, 46, XX. His parents and younger sister were healthy. His intelligence was normal (IQ 92) and he had no other anomalies. The behavior, growth and development were all normal. His testes were >4ml and the penis was 5 cm. Ultrasound and MRI did not show internal female genitals, while confirming right Kidney Hypoplasia (as did the DMSA scan). ACTH test showed normal basal and stimulated 17OH-progesterone excluding a form of 46XX DSD due to 21-hydroxylase deficiency. 11-DOC and 11S were normal at both baseline and after ACTH stimulation, excluding 11-hydroxylase deficiency. Cortisol levels were in the mid normal range at baseline and responded to stimulation, excluding primary adrenal insufficiency. Androstenedione, The hCG test found testosterone in the low normal range for male sex and age at baseline. It rised up to 146 ng/mL indicating the presence of functional Leydig cells targeted by hCG. The stimulated ratio T:DHT was 5.6, not supporting 5 alpha-reductase deficiency. SNP array for copy number variations (CNV’s) showed a unique 550 kb duplication involving SOX3, RP1–177G6, and CDR1 genes, and the microRNA MIR320D2. This CNV was absent in 13,839 controls. Conclusions A SRY negative 46, XX male with renal hypodysplasia was found to have an exceedingly rare duplication involving the SOX-3 gene, proving its role in sex determination and suggesting its evolvement in Kidney development.
Ali G. Gharavi - One of the best experts on this subject based on the ideXlab platform.
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740 Duplication of the Sox3 Gene in a Sry Negative 46, XX Male
Archives of Disease in Childhood, 2012Co-Authors: Zoran Gucev, Ali G. Gharavi, Simone Sanna-cherchi, Felix G. Riepe, Velibor TasicAbstract:Case presentation An 11 old patient with Hypoplasia of the right Kidney and hypospadias was found to be SRY negative, 46, XX. His parents and younger sister were healthy. His intelligence was normal (IQ 92) and he had no other anomalies. The behavior, growth and development were all normal. His testes were >4ml and the penis was 5 cm. Ultrasound and MRI did not show internal female genitals, while confirming right Kidney Hypoplasia (as did the DMSA scan). ACTH test showed normal basal and stimulated 17OH-progesterone excluding a form of 46XX DSD due to 21-hydroxylase deficiency. 11-DOC and 11S were normal at both baseline and after ACTH stimulation, excluding 11-hydroxylase deficiency. Cortisol levels were in the mid normal range at baseline and responded to stimulation, excluding primary adrenal insufficiency. Androstenedione, The hCG test found testosterone in the low normal range for male sex and age at baseline. It rised up to 146 ng/mL indicating the presence of functional Leydig cells targeted by hCG. The stimulated ratio T:DHT was 5.6, not supporting 5 alpha-reductase deficiency. SNP array for copy number variations (CNV’s) showed a unique 550 kb duplication involving SOX3, RP1–177G6, and CDR1 genes, and the microRNA MIR320D2. This CNV was absent in 13,839 controls. Conclusions A SRY negative 46, XX male with renal hypodysplasia was found to have an exceedingly rare duplication involving the SOX-3 gene, proving its role in sex determination and suggesting its evolvement in Kidney development.
Simone Sanna-cherchi - One of the best experts on this subject based on the ideXlab platform.
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740 Duplication of the Sox3 Gene in a Sry Negative 46, XX Male
Archives of Disease in Childhood, 2012Co-Authors: Zoran Gucev, Ali G. Gharavi, Simone Sanna-cherchi, Felix G. Riepe, Velibor TasicAbstract:Case presentation An 11 old patient with Hypoplasia of the right Kidney and hypospadias was found to be SRY negative, 46, XX. His parents and younger sister were healthy. His intelligence was normal (IQ 92) and he had no other anomalies. The behavior, growth and development were all normal. His testes were >4ml and the penis was 5 cm. Ultrasound and MRI did not show internal female genitals, while confirming right Kidney Hypoplasia (as did the DMSA scan). ACTH test showed normal basal and stimulated 17OH-progesterone excluding a form of 46XX DSD due to 21-hydroxylase deficiency. 11-DOC and 11S were normal at both baseline and after ACTH stimulation, excluding 11-hydroxylase deficiency. Cortisol levels were in the mid normal range at baseline and responded to stimulation, excluding primary adrenal insufficiency. Androstenedione, The hCG test found testosterone in the low normal range for male sex and age at baseline. It rised up to 146 ng/mL indicating the presence of functional Leydig cells targeted by hCG. The stimulated ratio T:DHT was 5.6, not supporting 5 alpha-reductase deficiency. SNP array for copy number variations (CNV’s) showed a unique 550 kb duplication involving SOX3, RP1–177G6, and CDR1 genes, and the microRNA MIR320D2. This CNV was absent in 13,839 controls. Conclusions A SRY negative 46, XX male with renal hypodysplasia was found to have an exceedingly rare duplication involving the SOX-3 gene, proving its role in sex determination and suggesting its evolvement in Kidney development.
