Publications by authors named "Garry L Warne"

24 Publications

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Management of disorders of sex development - With a focus on development of the child and adolescent through the pubertal years.

Best Pract Res Clin Endocrinol Metab 2019 06 27;33(3):101297. Epub 2019 Jul 27.

Department of Paediatrics, Faculty of Medicine and Health Sciences, University of Melbourne, Melbourne, Australia. Electronic address:

Disorders of sex development, congenital conditions in which chromosomal, gonadal or anatomic sex is atypical at birth, require urgent assessment by a multidisciplinary team, to define whether there is a life threatening disorder of congenital adrenal hyperplasia or a healthy child with a complex condition. Uncertainty, stigma and taboo complicate counselling which must be knowledgeable, comprehensive and sensitive to different circumstances, religions and cultures. This articles will discuss clinical and genetic diagnosis, decisions regarding sex of rearing, ethical dilemmas, medical management of the infant and of the child or adolescent presenting for the first time with a DSD. Surgical options, timing and management are outlined.
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http://dx.doi.org/10.1016/j.beem.2019.101297DOI Listing
June 2019

Another Look at Hereditary Partial Androgen Insensitivity Syndrome in an Indigenous Community in the Northern Territory of Australia.

J Paediatr Child Health 2017 12;53(12):1246-1247

Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/jpc.13731DOI Listing
December 2017

Fertility in Turner syndrome.

Clin Endocrinol (Oxf) 2013 Nov 4;79(5):606-14. Epub 2013 Sep 4.

Department of Endocrinology and Diabetes, Royal Children's Hospital Melbourne, Melbourne, Vic., Australia; Murdoch Childrens Research Institute, Melbourne, Vic., Australia; University of Melbourne, Melbourne, Vic., Australia.

There is increasing interest in fertility and use of assisted reproductive technologies for women with Turner syndrome (TS). Current parenting options include adoption, surrogacy, and spontaneous and assisted reproduction. For women with TS, specific risks of pregnancy include higher than usual rates of spontaneous abortion, foetal anomaly, maternal morbidity and mortality. Heterologous fertility assistance using oocytes from related or unrelated donors is an established technique for women with TS. Homologous fertility preservation includes cryopreservation of the patient's own gametes prior to the progressive ovarian atresia known to occur: preserving either mature oocytes or ovarian tissue containing primordial follicles. Mature oocyte cryopreservation requires ovarian stimulation and can be performed only in postpubertal individuals, when few women with TS have viable oocytes. Ovarian tissue cryopreservation, however, can be performed in younger girls prior to ovarian atresia - over 30 pregnancies have resulted using this technique, however, none in women with TS. We recommend consideration of homologous fertility preservation techniques in children only within specialized centres, with informed consent using protocols approved by a research or clinical ethics board. It is essential that further research is performed to improve maternal and foetal outcomes for women with TS.
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http://dx.doi.org/10.1111/cen.12288DOI Listing
November 2013

Advice on the management of ambiguous genitalia to a young endocrinologist from experienced clinicians.

Semin Reprod Med 2012 Oct 8;30(5):339-50. Epub 2012 Oct 8.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8857, USA.

The birth of a child with ambiguous genitalia is a challenging and distressing event for the family and physician and one with life-long consequences. Most disorders of sexual differentiation (DSD) associated with ambiguous genitalia are the result either of inappropriate virilization of girls or incomplete virilization of boys. It is important to establish a diagnosis as soon as possible, for psychological, social, and medical reasons, particularly for recognizing accompanying life-threatening disorders such as the salt-losing form of congenital adrenal hyperplasia. In most instances, there is sufficient follow-up data so that making the diagnosis also establishes the appropriate gender assignment (infants with congenital adrenal hyperplasia, those with androgen resistance syndromes), but some causes of DSD such as steroid 5α-reductase 2 deficiency and 17β-hydroxysteroid dehydrogenase deficiency are associated with frequent change in social sex later in life. In these instances, guidelines for sex assignment are less well established.
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http://dx.doi.org/10.1055/s-0032-1324717DOI Listing
October 2012

Hormone treatment of gender identity disorder in a cohort of children and adolescents.

Med J Aust 2012 May;196(9):578-81

Royal Children's Hospital, Melbourne, VIC.

Objective: To describe the experience of hormone treatment of gender identity disorder (GID) in children and adolescents within a specialist clinic.

Design, Patients And Setting: Cohort study by medical record review of children aged 0-17 years referred during 2003-2011 for management at the GID clinic in a tertiary paediatric referral centre - the Royal Children's Hospital, Melbourne, Victoria.

Main Outcome Measures: Clinical characteristics of the patient population, hormone treatment provided, frequency of referrals with time.

Results: Thirty-nine children and adolescents were referred for gender dysphoria. Seventeen individuals were pubertal with persistent GID, and were considered eligible for hormone treatment. Seven patients, comprising three biological males and four biological females, had legally endorsed hormone treatment. In this group, gender dysphoria was first noted at 3-6 years of age. Hormone treatment with GnRH analogue to suppress pubertal progression (phase 1) was given at 10-16 years of age. Treatment with cross-sex hormones (phase 2) was given at 15.6-16 years. One patient purchased cross-sex hormone treatment overseas. One patient received oestrogen and progesterone for menstrual suppression before phase 1. The annual frequency of new referrals increased continuously over the study period.

Conclusions: Hormone treatment for pubertal suppression and subsequent gender transition needs to be individualised within stringent protocols in multidisciplinary specialist units.
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http://dx.doi.org/10.5694/mja12.10222DOI Listing
May 2012

Ethical and legal aspects of management for disorders of sex development.

J Paediatr Child Health 2011 Sep;47(9):661-3

Department of Endocrinology and Diabetes, Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia.

Intense controversy surrounds the management of disorders of sex development, particularly in relation to the validity of parental consent for genital surgery and the removal of gonadal tissue carried out during infancy or childhood. Past practices have been heavily criticised on ethical grounds by patient advocacy organisations, who have demanded a moratorium on these kinds of operations unless authorised by a court. Some doctors and hospital administrators have been influenced by the controversy and have referred cases to the Family Court of Australia, where a series of judgements have now established legal precedents that apply across Australia, restricting the circumstances in which parents can give consent for surgery. An alternative approach is to use a hospital-based Clinical Ethics Response Group and, if necessary, Clinical Ethics Committee, which has lay and legal representatives as well as health professionals, as a semi-independent committee of review. Finding a solution that protects the human rights and best interests of children is an ongoing challenge.
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http://dx.doi.org/10.1111/j.1440-1754.2011.02164.xDOI Listing
September 2011

Ethical principles: an essential part of the process in disorders of sex development care.

Horm Res Paediatr 2011 4;76(5):367-8. Epub 2011 Aug 4.

Children's Bioethics Centre, Royal Children's Hospital, Melbourne, Vic., Australia.

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http://dx.doi.org/10.1159/000328316DOI Listing
March 2012

Ethical principles for the management of infants with disorders of sex development.

Horm Res Paediatr 2010 12;74(6):412-8. Epub 2010 Aug 12.

Children's Bioethics Centre, Royal Children's Hospital, Melbourne, Vic, Australia. l.gillam @ unimelb.edu.au

The Fifth World Congress on Family Law and Children's Rights (Halifax, August 2009) adopted a resolution endorsing a new set of ethical guidelines for the management of infants and children with disorders of sex development (DSD) [www.lawrights.asn.au/index.php?option = com_content&view = article&id = 76&Itemid = 109]. The ethical principles developed by our group were the basis for the Halifax Resolution. In this paper, we outline these principles and explain their basis. The principles are intended as the ethical foundation for treatment decisions for DSD, especially decisions about type and timing of genital surgery for infants and young children. These principles were formulated by an analytic review of clinician reasoning in particular cases, in relation to established principles of bioethics, in a process consistent with the Rawlsian concept of reflective equilibrium as the method for building ethical theory. The principles we propose are: (1) minimising physical risk to child; (2) minimising psychosocial risk to child; (3) preserving potential for fertility; (4) preserving or promoting capacity to have satisfying sexual relations; (5) leaving options open for the future, and (6) respecting the parents' wishes and beliefs.
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http://dx.doi.org/10.1159/000316940DOI Listing
April 2011

Disorders of sex development: current understanding and continuing controversy.

Med J Aust 2009 Jun;190(11):612-3

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http://dx.doi.org/10.5694/j.1326-5377.2009.tb02586.xDOI Listing
June 2009

Disorders of sex development (DSDs), their presentation and management in different cultures.

Rev Endocr Metab Disord 2008 Sep 17;9(3):227-36. Epub 2008 Jul 17.

Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Australia.

The way disorders of sex development (DSD) are viewed and managed in different cultures varies widely. They are complex conditions and even well-educated lay people find them difficult to understand, but when families are very poor and lacking in basic education, and the health system is starved of resources, traditional beliefs, folk remedies and prejudice combine to make the lives of children and adults with DSD extremely difficult and sad. Rumour and discrimination isolate them from their communities and they become devalued. People with DSDs desire the same things in life as everyone else-to find someone who will love them, to be valued as human beings, to feel at home in their own bodies, to be able to have satisfactory sexual relations should these be desired, to be able to trust their medical advisers and to be integrated into the general community. Long term outcome studies have been published from many countries, but these studies have not necessarily been critical of the values that underpinned the type of treatment given to the patients. There is a need for standardized instruments that would allow a true comparison of the quality of outcomes from the patients' perspective. Much could be done to improve equity between rich and poor countries for the benefit of people with DSDs. A focus on developing cheap, robust diagnostic tests, making essential medicines available for all, training surgeons to do better operations, educating health professionals, families and the general community in order to break down prejudice against people with DSDs, and training mental health workers in this specialized field, would do much to alleviate the burden of the condition.
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http://dx.doi.org/10.1007/s11154-008-9084-2DOI Listing
September 2008

Double-strand DNA break repair with replication slippage on two strands: a novel mechanism of deletion formation.

Hum Mutat 2006 May;27(5):483-9

Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Australia.

We have characterized an unusual family with two different androgen receptor (AR) gene deletions, in which we propose a novel mechanism of deletion formation has occurred. Affected individuals have the X-linked disorder androgen insensitivity syndrome, and we previously showed that different family members have deletions of different exons of the AR gene. We have now fully sequenced the deletions from affected individuals, and confirmed the presence of different deletions in different affected family members. Most affected and heterozygote individuals have a 4,430-bp deletion of exon 5 that occurred between repeated GTGGCAT motifs in introns 4 and 5. One affected hemizygous individual has a 4,033-bp deletion of exons 6 and 7 that occurred between repeated CCTC motifs in introns 5 and 7. The intron 5 breakpoint junctions of the two deletions are only 11 bp apart. Surprisingly, the maternal grandmother of the original index case was found to be mosaic for both deletional events, as well as having the normal AR gene. Karyotyping ruled out 47,XXX trisomy, indicating triple mosaicism for the two different deleted AR alleles and a normal AR allele. This triple mosaicism must have occurred early in embryonic development, as both deletions were passed on to different children. Based on these findings, we propose a novel mechanism of deletion formation. We suggest that during AR gene replication, a double strand DNA break occurred in intron 5, and that a variant of replication slippage occurred on both newly synthesized strands between the repeat motifs of microhomology, leading to the formation of the two different AR gene deletions.
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http://dx.doi.org/10.1002/humu.20327DOI Listing
May 2006

Growth in congenital adrenal hyperplasia.

Indian J Pediatr 2006 Jan;73(1):89-93

Department of Endocrinology and Diabetes, Murdoch Children's Research Institute, Royal Children's Hospital,Parkville, Victoria, Australia.

Individuals with congenital adrenal hyperplasia (CAH) are shorter, on an average, than the general population. A recent meta analysis of final height in CAH indicated that the height deficit is typically 1 to 2 standard deviations below the mean in both males and females. Growth in CAH due to 21-hydroxylase deficiency is influenced by a number of factors, related both to the underlying disease and its treatment. In general, males with the simple virilising form have the poorest height prognosis. This relates in part to late diagnosis and treatment and the bone age advancement seen in individuals with untreated postnatal androgen excess. Obesity in CAH patients also appears to be correlated with reduced height potential. Glucocorticoid treatment which is vital for cortisol replacement, prevention of adrenal crises and androgen suppression, results in growth inhibition when administered in larger doses. Current evidence suggests that infancy and peripubertal periods are the time periods where height outcome is most sensitive to glucocorticoid dose. More recent estimates of physiological cortisol secretion rates indicate that standard cortisol replacement schedules may result in overtreatment. In addition, dose titration to achieve complete androgen suppression and normalization of 17-hydroxyprogesterone is likely to result in overtreatment and consequent growth impairment. Optimization of current treatment may lead to further improvements in height prognosis. The potential benefits of more complex treatment regimes, using aromatase inhibitors and antiandrogens, in combination with a reduced glucocorticoid dose remain uncertain.
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http://dx.doi.org/10.1007/BF02758268DOI Listing
January 2006

Growth in precocious puberty.

Indian J Pediatr 2006 Jan;73(1):81-8

Department of Endocrinology and Diabetes Royal Children's Hospital, Parkville, Victoria, Australia.

Growth in precocious puberty is a subject of concern to families and clinicians alike. The definition of precocious puberty and the role of obesity in the age of onset have also been areas of debate since the Lawson Wilkins Society recommended a lowering of the age of onset of precocious puberty in US girls. An understanding of growth patterns in normal children with earlier or later onset of puberty and the variable rate of progression between individuals with central precocious puberty as well as the imprecision in available height prediction methods are important in assessing height outcomes in this condition. In the absence of randomised controlled trials in this area, only qualified conclusions about the effectiveness of interventions can be drawn. In general, it appears that height outcome is not compromised in untreated slowly progressive variants of central precocious puberty. In rapidly progressing central precocious puberty in girls, gonadotrophin releasing hormone agonists (GnRH agonists) appear to increase final height by about 5 cm in girls treated before the age of eight, but there is no height benefit in those treated after eight years. Scanly data is available to assess treatment effects in boys. GnRH agonists appear to be relatively safe. The decision to treat central precocious puberty should take into account rate of progression of pubertal changes as well as biochemical markers and may need to address other factors (for example psychosocial and behavioural issues) as well as height outcome.
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http://dx.doi.org/10.1007/BF02758267DOI Listing
January 2006

Autopsy diagnosis of 21-hydroxylase deficiency CAH in a case of apparent SIDS.

Pediatr Dev Pathol 2005 May-Jun;8(3):397-401. Epub 2005 Jul 14.

Centre for Hormone Research, Royal Children's Hospital, Melbourne, Parkville Victoria, Australia.

A 5-month-old boy with no history of vomiting, early sexual development, or noticeable significant illness was found dead in bed. Autopsy demonstrated bilateral adrenal hyperplasia unequivocally shown on biochemical testing of blood and urine to be due to 21-hydroxylase deficiency. Genetic analysis of the CYP21 gene showed compound heterozygosity; 1 allele contained a pseudogene sequence (gene conversion) and the other contained a previously described I172N point mutation. On theoretical grounds, the genotype would have been expected to cause simple virilizing congenital adrenal hyperplasia but, because no other cause of death could be found, it is possible that it caused a fatally severe loss of enzyme activity in this child. If this assumption is valid, newborn screening would have prevented this death, had it been available.
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http://dx.doi.org/10.1007/s10024-005-0004-0DOI Listing
October 2005

Age-dependent differences in androgen binding affinity in a family with spinal and bulbar muscular atrophy.

Neurol Res 2005 Jul;27(5):548-51

Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia.

Objectives: To investigate androgen receptor (AR) function in spinal and bulbar muscular atrophy (SBMA).

Methods: A kindred was identified with five individuals carrying the AR gene CAG repeat expansion that causes SBMA. Androgen binding was measured in cultured genital skin fibroblasts from three affected individuals. One newborn, pre-symptomatic, individual showed normal androgen binding, but two older, symptomatic individuals showed a decrease in androgen binding affinity. This difference was not related to AR CAG repeat size, as all affected individuals in this kindred had 49 repeats (normal range 6-35). Post-mortem analysis in one subject confirmed the signs of androgen insufficiency in the testis, with marked seminiferous tubule atrophy, and the absence of germinal cells. The characteristic neuronal depletion in the anterior horn gray matter was also observed.

Conclusion: This report raises the possibility that age- or puberty-related changes in androgen binding could occur, which could potentially contribute to the progressive development of androgen resistance in affected men.
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http://dx.doi.org/10.1179/016164105X39851DOI Listing
July 2005

Hormonal therapies for individuals with intersex conditions: protocol for use.

Treat Endocrinol 2005 ;4(1):19-29

Centre for Hormone Research, Royal Children's Hospital, Melbourne, Victoria, Australia.

Hormonal therapy forms part of the treatment of every intersex condition. For some conditions, such as salt-wasting congenital adrenal hyperplasia, hormonal replacement therapy is life saving because hormones necessary for survival (cortisol and aldosterone) are replaced. In contrast, other hormones such as androgens or mineralocorticoids are secreted in excessive amounts in congenital adrenal hyperplasia due to an enzyme imbalance, and the role of hormonal therapy is to suppress the unwanted hormone excess by exerting negative feedback. For patients with one of the many causes of hypogonadism, sex hormone replacement therapy may be prescribed to stimulate sexual development: growth of a hypoplastic penis in a young boy, pubertal changes (male or female), psychosexual development, and adult sexual behavior. It has equally important and highly beneficial effects on bone mineral density. Hormonal therapy is also used to treat the unborn child. For the last 20 years, prenatal dexamethasone treatment administered to the pregnant woman has been used to prevent the development of ambiguous genitalia in females with 21-hydroxylase deficiency. Outcome studies show this treatment to be well tolerated and, in general, efficacious. Intersex conditions are, however, difficult to treat because they may intrinsically perturb complex aspects of the person's gender identity, gender-role behavior, sexual orientation, sexual functioning, and psychologic adjustment. Furthermore, decisions made about the sex of an infant by doctors and parents do not always turn out to be correct; the person may grow up feeling uncertain about his or her gender identity, or worse still, harbor a sense of outrage about their life and treatment experiences. Such a person will have definite views about hormonal therapy when the time comes and skillful counseling will be needed. A vigorous debate about ethical aspects of current medical practices relating to intersex conditions has been waged for the last 7 years between certain patient advocacy organizations and the medical profession, and is expected to continue for some time. The quality of the debate will be improved by evidence. The results of a number of long-term follow-up studies have been published, and more are expected. The published studies show mixed, but mainly encouraging, results.
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http://dx.doi.org/10.2165/00024677-200504010-00003DOI Listing
March 2005

Increased frequency of long androgen receptor CAG repeats in male breast cancers.

Breast Cancer Res Treat 2004 Dec;88(3):239-46

Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, VIC, 3084, Australia.

We have investigated the possible link between androgen hyposensitivity caused by long androgen receptor (AR) CAG repeats, and breast carcinogenesis, in men. AR gene mutations have been described in men with androgen insensitivity syndrome and breast carcinoma, and some studies have shown long CAG repeats are associated with increased risk of breast cancer in women. DNA was isolated from male breast cancer biopsies, and the AR CAG repeat sized. Forty one male breast cancer samples were studied, including one sample from a man with spinal and bulbar muscular atrophy (SBMA), which is caused by an AR CAG repeat expansion. The man with breast cancer and SBMA had 49 CAG repeats (normal range 6-35), but all other breast cancer samples had repeats within the normal range. The frequency of CAG repeats > or =24 was significantly higher in the breast cancer group (excluding the SBMA subject) than in the normal population (p<0.05), and was more marked in grade I and II tumors (p=0.001). There was no correlation between AR CAG repeat length and age at diagnosis. In conclusion, longer AR CAG repeats are more common in men with breast cancer than in the control male population. Androgen hyposensitivity, caused by long AR CAG repeats, may increase the risk of breast cancer in men.
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http://dx.doi.org/10.1007/s10549-004-0781-6DOI Listing
December 2004

Application of differential display in the identification of androgen-regulated genes.

Endocr Res 2004 Feb;30(1):69-82

Centre for Hormone Research, Murdoch Children's Research Institute, University of Melbourne, Royal Children's Hospital, Victoria, Australia.

Identification of androgen-regulated genes in neurons is an important step in understanding the mechanisms involved in androgen action. The aim of the current study was to identify androgen-responsive genes in the neural cells using the technique of differential display reverse transcription polymerase chain reaction (DDRT-PCR) on the human neuroblastoma cell line, SK-N-MC. Using this analysis, 18 putatively androgen-regulated cDNA species were identified, ranging in size from 280 to 800 bp. Of these, 14 were found to be negatively regulated and 4 positively regulated by androgens. Only 12 were successfully re-amplified, and of these, 8 were found to contain multiple species of cDNA fragments. When Northern analysis was conducted using the 21 different cDNA fragments as probes, only one was found to confirm the androgen regulation demonstrated via DDRT-PCR. While this putatively regulated gene remains to be fully characterized, future studies of may provide insights into the molecular mechanisms governing androgen action in neural cells.
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http://dx.doi.org/10.1081/erc-120029886DOI Listing
February 2004

Novel androgen receptor gene mutations in Australian patients with complete androgen insensitivity syndrome.

Hum Mutat 2004 Mar;23(3):287

Department of Medicine (AH/NH), University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia.

We have identified androgen receptor (AR) gene mutations in eight Australian subjects with complete androgen insensitivity syndrome (AIS). Four individuals, from three families, have novel mutations that introduce premature termination codons. Two siblings have the nonsense mutation Glu681X, and another subject has the nonsense mutation p.Ser884X. The other subject has a CA insertion at codon 829 (c.2847_2848insCA), causing a frameshift mutation that introduces four nonsense amino acids prior to a Stop codon. All the termination codons occur in the ligand binding domain, and cause reduced androgen binding in patient genital skin fibroblasts. Four further patients have missense mutations. One subject has two different mutations, p.Ala645Asp in the hinge region of the receptor, and p.Arg752Gln in the ligand binding domain. Both these mutations have previously been reported in patients with AIS, but the combination of these two mutations in one subject is unique. Another subject has a novel c.2533G>C transversion at the first nucleotide in exon 5, introducing the amino acid change p.Gly724Ala at a highly conserved residue in the ligand binding domain. Androgen binding is normal in fibroblasts from this subject, although other point mutations at this amino acid totally abolish binding. Two other subjects have mutations previously described as causing AIS, namely p.Arg779Trp and p.Val889Met substitutions in the ligand binding domain of the receptor. The p.Arg779Trp mutation is associated with the detection of a truncated AR protein in this patient's fibroblasts, suggesting the mutation renders the receptor susceptible to proteolysis.
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http://dx.doi.org/10.1002/humu.9221DOI Listing
March 2004

Molecular endocrinology of sex differentiation.

Semin Reprod Med 2002 Aug;20(3):169-80

Centre for Hormone Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.

Differentiation of a testis or an ovary from a bipotential gonad is a complex developmental process involving various genes and hormones. Similarly, internal and external genital organs develop from an indeterminate stage from the complex differentiation of Wolffian and Müllerian ducts. Differentiation of the Wolffian ducts, urogenital sinus, and external genitalia is androgen dependent. Female sex differentiation appears to be a more passive process that is independent of estrogen. This article reviews the process of differentiation of the gonads and the genitalia and the factors affecting it. In addition, a clinical approach to patients with sexual ambiguity or sex reversal is discussed.
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http://dx.doi.org/10.1055/s-2002-35381DOI Listing
August 2002

Massive ovarian edema causing early puberty.

J Pediatr Endocrinol Metab 2002 Jun;15(6):861-4

Department of Endocrinology and Diabetes, Royal Children's Hospital, Parkville, Victoria, Australia.

Massive ovarian edema is a rare tumor-like condition found predominantly in young women. Patients usually present with abdominal pain and/or abdominal mass. Pre-operative diagnosis is often difficult. Awareness of this rare and benign lesion in young women may allow conservative management and prevention of oophorectomy in some patients.
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http://dx.doi.org/10.1515/jpem.2002.15.6.861DOI Listing
June 2002

Increased gene dosage at Xq26-q27 is associated with X-linked hypopituitarism.

Genomics 2002 Apr;79(4):553-9

Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia, 3052.

We have identified a novel interstitial duplication at Xq26.1-q27.3 in a previously reported family with X-linked recessive hypopituitarism [1]. Mapping of the duplication was carried out using interphase FISH analysis of over 60 bacterial genomic clones from Xq25-q28. The proximal and distal breakpoints of the duplication are contained within the 432N13 and 91O18 clones, respectively, and are separated by approximately 9 Mb. Comparison with a recently published 13-Mb duplication in another XH family [2] indicated that the duplication break-points in these families were different. Therefore, we conclude that X-linked hypopituitarism is caused by increased dosage of a gene that is critical for pituitary development and that the causative gene is located within the 9-Mb duplicated region that we have defined.
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http://dx.doi.org/10.1006/geno.2002.6741DOI Listing
April 2002