Publications by authors named "Daniela Brindusa Gorduza"

5 Publications

  • Page 1 of 1

Mayer-Rokitansky-Künster-Hauser syndrome due to 2q12.1q14.1 deletion: PAX8 the causing gene?

Eur J Med Genet 2020 Apr 12;63(4):103812. Epub 2019 Nov 12.

CHU Lille, Institut de Génétique Médicale, F-59000, Lille, France; CHU Lille, Clinique de Génétique - Guy Fontaine, F-59000, Lille, France. Electronic address:

Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) is a rare malformative disorder, characterized by congenital aplasia of the uterus and the upper two thirds of the vagina (MIM #277000). For a majority of patients, the disorder remained without identified genetic cause. However, four recurrent microdeletions, i.e. 1q21.1-16p11.2-17q12 and 22q11.21, as well as variants in genes contained in these loci, have been identified in a small number of cases. We describe an additional patient with 2q12.1q14.1 microdeletion, showing MRKH and congenital hypothyroidism due to thyroid gland hypoplasia. The patient received a dual diagnosis with microdeletion of SHOX locus in addition to the 2q12.1q14.1 microdeletion. Literature review and database analysis has enabled us to identify 5 OMIM morbid genes: CKAP2L, IL1B, IL1RN, IL36RN and PAX8. Among these, PAX8 (Paired Box Gene 8), a transcriptional factor part of the paired-box family, plays a key role in the development of the thyroid gland, kidneys and Müllerian derivatives. We discuss here the role of PAX8 and speculate on the possible involvement of PAX8 in MRKH. In this study, we report a second case of 2q12.1q14.1 microdeletion, involving PAX8 as a gene associated with Müllerian agenesis in a MRKH I and hypothyroidism. Further studies will confirm the direct participation of PAX8 in gene target sequencing in a population of MRKH with hypothyroidism.
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http://dx.doi.org/10.1016/j.ejmg.2019.103812DOI Listing
April 2020

Reversion SAMD9 Mutations Modifying Phenotypic Expression of MIRAGE Syndrome and Allowing Inheritance in a Usually Disorder.

Front Endocrinol (Lausanne) 2019 11;10:625. Epub 2019 Sep 11.

Laboratoire de Biochimie et Biologie Moléculaire Grand Est, UM Pathologies Endocriniennes Rénales Musculaires et Mucoviscidose, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.

MIRAGE (Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital phenotypes, Enteropathy) syndrome is a severe multisystem disorder with high mortality. It is caused by a heterozygous gain of function mutation in the growth repressor gene . The increasing number of reported cases displays a spectrum of phenotypes that may be explained by an adaptation mechanism, with appearance of a somatic second hit mutation with revertant effects. To determine the genetic basis of the MIRAGE syndrome rapidly corrected in a living and healthy 46,XY patient. A 46,XY patient born with growth restriction and disorders of sex development had thrombocytopenia and necrotizing enterocolitis during the neonatal period suggestive of the syndrome. Faced with the rapid improvement of the patient's phenotype, an adaptation mechanism was sought by repeating genetic analysis at different ages; her parents also underwent genetic analysis. The previously described p.(Thr778Ile) mutation was identified and surprisingly transmitted by the asymptomatic mother in this usually syndrome. To explain the rapid improvement of the patient's phenotype and absence of symptoms in the mother, an adaptation mechanism was sought. For the mother, a non-sense mutation was found (p.(Arg221)) in , and most likely appeared . It was not transmitted to her child. The child harbored a different non-sense mutation (p.(Arg285)) that most likely appeared near day 20. We show that pathogenic variants can be inherited from a healthy parent as the adaptation mechanism may arise early in life and mask symptoms. Presence of revertant mosaicism mutations could explain "incomplete penetrance" in other disease. For a better management and outcomes in patients, appearance of this natural gene therapy should be sought by repeating genetic analysis.
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http://dx.doi.org/10.3389/fendo.2019.00625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749008PMC
September 2019

[Atypical genital development and tumor risk].

Bull Cancer 2019 May 23;106(5):461-467. Epub 2019 Mar 23.

Groupement hospitalier Est, hospices Civils de Lyon, institut Multisite de pathologie, 69500 Bron, France.

Atypical genital development (AGD), also called disorders of sex development are a set of miscellaneous pathologies who have in common a morphological and/or functional abnormality of the internal and/or external genital organs. The Chicago classification identifies 3 major groups based on karyotype, hormone balance and genetic studies. Some AGD predispose to the occurrence of tumors, mainly malignant germ cell tumors. The tumor risk depends on many factors: the type of AGD, the position of the gonad, the age of the patient, the phenotype, the function of the gonad and the presence of germ cells in the gonad. AGD with the highest tumor risk are those with gonadal dysgenesis, implying an incomplete differentiation of the bipotential gonad (dysplasia). Monitoring of patients with AGD and indication of prophylactic gonadectomies should be individualized according to tumor risk.
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http://dx.doi.org/10.1016/j.bulcan.2019.01.018DOI Listing
May 2019

Surgery in disorders of sex development (DSD) with a gender issue: If (why), when, and how?

J Pediatr Urol 2016 Jun 9;12(3):139-49. Epub 2016 Apr 9.

Penn State Hershey Pediatric Endocrinology, PA, USA.

Ten years after the consensus meeting on disorders of sex development (DSD), genital surgery continues to raise questions and criticisms concerning its indications, its technical aspects, timing and evaluation. This standpoint details each distinct situation and its possible management in 5 main groups of DSD patients with atypical genitalia: the 46,XX DSD group (congenital adrenal hyperplasia); the heterogeneous 46,XY DSD group (gonadal dysgenesis, disorders of steroidogenesis, target tissues impairments …); gonosomic mosaicisms (45,X/46,XY patients); ovo-testicular DSD; and "non-hormonal/non chromosomal" DSD. Questions are summarized for each DSD group with the support of literature and the feed-back of several world experts. Given the complexity and heterogeneity of presentation there is no consensus regarding the indications, the timing, the procedure nor the evaluation of outcome of DSD surgery. There are, however, some issues on which most experts would agree: 1) The need for identifying centres of expertise with a multidisciplinary approach; 2) A conservative management of the gonads in complete androgen insensitivity syndrome at least until puberty although some studies expressed concerns about the heightened tumour risk in this group; 3) To avoid vaginal dilatation in children after surgical reconstruction; 4) To keep asymptomatic mullerian remnants during childhood; 5) To remove confirmed streak gonads when Y material is present; 6) It is likely that 46,XY cloacal exstrophy, aphallia and severe micropenis would do best raised as male although this is based on limited outcome data. There is general acknowledgement among experts that timing, the choice of the individual and irreversibility of surgical procedures are sources of concerns. There is, however, little evidence provided regarding the impact of non-treated DSD during childhood for the individual development, the parents, society and the risk of stigmatization. The low level of evidence should lead to design collaborative prospective studies involving all parties and using consensual protocols of evaluation.
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http://dx.doi.org/10.1016/j.jpurol.2016.04.001DOI Listing
June 2016

Surgical options in disorders of sex development (dsd) with ambiguous genitalia.

Best Pract Res Clin Endocrinol Metab 2010 Apr;24(2):311-24

Department of Paediatric Urology and Surgery, Hôpital Mère-Enfants, and Claude-Bernard University, 69677 Bron, France.

Disorders of sexual development (DSD) include three main groups of patients: (1) The virilised 46,XX DSD essentially represented by congenital adrenal hyperplasia (CAH) ; (2) The undervirilised 46,XY DSD essentially represented by hypospadias; and (3) the chromosomic jigsaws essentially represented by mixed gonadal dysgenesis. It is in this last group that gender assignment remains a difficult decision involving various indicators, which can be split into four categories: (1) the inside sex (i.e., genes, hormones and target tissues); (2) the outside sex (i.e., anatomy of genitalia including size of the genital tubercle, mullerian cavity and potential adult height of the patient); (3) the functional sex (i.e., potential sexuality and fertility); and (4) and the social sex (i.e., the cultural medium in which the child is brought up). The challenge is to outline the future individual identity of the child in the postnatal period using these indicators. Current evolutions of surgical techniques of 'feminisation' and 'masculinisation' are described as well as their outcomes.
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http://dx.doi.org/10.1016/j.beem.2009.10.004DOI Listing
April 2010