A novel SOX9 mutation, 972delC, causes 46,XY sex-reversed campomelic dysplasia with nephrocalcinosis, urolithiasis, and dysgerminoma.
ABSTRACT An 8-year-old phenotypic female with campomelic dysplasia (CD) and 46,XY sex-reversal presented with renal colic. Medullary nephrocalcinosis, urolithiasis, and renal malrotation were diagnosed by computed tomographic scanning. Pelvic sonogram identified an enlarged left gonad. Genetic testing revealed a novel SOX9 heterozygous deletion of a cytosine at nucleotide 972 (972delC), causing a frameshift at codon 200, introducing a stop codon 18 codons further downstream (P200fsX218). At laparoscopic gonadectomy, a left dysgerminoma was removed. This first reported case of dysgerminoma in a sex-reversed patient with CD who also had urolithiasis stresses the importance of prophylactic gonadectomy and urologic evaluations in this susceptible population.
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ABSTRACT: The organization known as ELPAT (Ethical, Legal and Psychological Aspects of Organ Transplantation) coordinated the distribution of an electronic questionnaire concerning the definition of extended criteria liver donation (ECD) and the implication for informed consent of transplant recipients to European liver transplant centers. Completed questionnaires were received from 30 centers in 13 countries. Twenty-eight centers accepted ECD liver donors. The criteria for defining a liver donor as ECD were: steatosis in 24 centers (85%); age up to 80 years in 23 centers (82%); serum sodium levels higher than 165 mmol/L in 17 centers (60%); intensive care unit stay with ventilation longer than 7 days in 16 centers (57%); serum glutamic oxalo-acitic transaminase levels higher than 90 U/L in 12 centers (42%); body mass indeces more than 30 in 10 centers (35%); serum glutamic pyruvic transaminase levels higher than 105 U/L in 10 centers (35%); serum bilirubin levels higher than 3 mg/dL in 10 centers (35%); and other criteria in 13 centers (46%). Twenty-three centers informed the transplant candidate of the ECD status of the donor: 10 centers (43%) when the patient registered for transplantation, 3 centers (14%) when an ECD liver became available, and 10 centers (43%) on both occasions. Ten centers required the liver transplant candidate to sign a special consent form. Ten centers informed the potential recipient of the donor's serology. Only three centers informed the potential recipient of any high risk behavior of the donor.Transplantation Proceedings 05/2011; 43(4):971-3. · 0.95 Impact Factor
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ABSTRACT: The SOX8 and SOX9 transcription factors are involved in, among others, sex differentiation, male gonad development and adult maintenance of spermatogenesis. Sox8(-/-) mice lacking Sox9 in Sertoli cells fail to form testis cords and cannot establish spermatogenesis. Although genetic and histological data show an important role for these transcription factors in regulating spermatogenesis, it is not clear which genes depend upon them at a genome-wide level. To identify transcripts that respond to the absence of Sox8 in all cells and Sox9 in Sertoli cells we measured mRNA concentrations in testicular samples from mice at 0, 6 and 18 days post-partum. In total, 621 and 629 transcripts were found at decreased or increased levels, respectively, at different time points in the mutant as compared to the control samples. These mRNAs were categorized as preferentially expressed in Sertoli cells or germ cells using data obtained with male and female gonad samples and enriched testicular cell populations. Five candidate genes were validated at the protein level. Furthermore, we identified putative direct SOX8 and SOX9 target genes by integrating predicted SOX-binding sites present in potential regulatory regions upstream of the transcription start site. Finally, we used protein network data to gain insight into the effects on regulatory interactions that occur when Sox8 and Sox9 are absent in developing Sertoli cells. The integration of testicular samples with enriched Sertoli cells, germ cells and female gonads enabled us to broadly distinguish transcripts directly affected in Sertoli cells from others that respond to secondary events in testicular cell types. Thus, combined RNA profiling signals, motif predictions and network data identified putative SOX8/SOX9 target genes in Sertoli cells and yielded insight into regulatory interactions that depend upon these transcription factors. In addition, our results will facilitate the interpretation of genome-wide in vivo SOX8 and SOX9 DNA binding data.Andrology 01/2013; · 3.37 Impact Factor
Article: Nefrocalcinosis en el niño[Show abstract] [Hide abstract]
ABSTRACT: La nefrocalcinosis, cuyo diagnóstico en la actualidad resulta sencillo gracias a la ecografía, no es excepcional en el niño ni en el lactante. Las etiologías son múltiples, pero implican casi todas un trastorno metabólico, a menudo de origen genético, a veces iatrogénico, que aumenta la excreción urinaria de calcio o de oxalato. Las causas más frecuentes varían en función de la edad. En el recién nacido y en el lactante se habla principalmente de «hipercalciuria del prematuro», cuyo origen, multifactorial, es en gran medida iatrogénico, tubulopatías de aparición precoz (acidosis tubular distal, síndrome de Bartter) y, afortunadamente muy rara, la hiperoxaluria primaria en su forma de aparición infantil. En el niño, las principales causas que hay que buscar son: la acidosis tubular distal, la hiperoxaluria primaria y las hipercalciurias de origen genético conocido (enfermedad de Dent, hipomagnesemia-hipercalciuria familiar) o también las causas «idiopáticas». Su evolución depende de la extensión de los depósitos cálcicos y sobre todo de la causa, es decir, de la posibilidad o no de parar el proceso de calcificación.EMC - Pediatría. 03/2013; 48(1):1–5.