The analysis of clinical manifestations and genetic mutations in Chinese boys with primary adrenal insufficiency

Department of Pediatrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Journal of pediatric endocrinology & metabolism: JPEM (Impact Factor: 1). 04/2012; 25(3-4):295-300. DOI: 10.1515/jpem-2011-0362
Source: PubMed


To analyze the clinical manifestations of primary adrenal insufficiency in Chinese boys, to investigate the prevalence of DAX1 and SF1 gene mutations, and to explore the association between gene mutations and clinical manifestations.
A total of 25 boys with primary adrenal insufficiency were enrolled. Mutational analysis of the DAX1 and SF1 genes was done by direct sequencing.
DAX1 gene mutations were found in 40% (10 of 25) of 46,XY phenotypic boys referred with adrenal insufficiency, and six of these were novel. One SF1 gene mutation was identified. These patients demonstrated diverse clinical presentations. There was no definite association between clinical manifestations and genetic mutations.
DAX1 gene mutations are a relatively frequent cause of primary adrenal insufficiency. In contrast, mutation in the SF1 gene is seldom found. There is no definite relationship between gene mutations and clinical manifestations.

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    • "Approximately 60 % of the boys with DAX1 mutations have an early onset of primary adrenal failure presenting with salt wasting in the first two months of life that can be misdiagnosed as CAH (11,27,28). In 25 Chinese infant boys with primary adrenal insufficiency, DAX1 gene mutations were found in 40% (29). Other cases are reported to have a more insidious presentation - symptoms becoming obvious later in childhood and which may be triggered by a stressful incident. "
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    ABSTRACT: Adrenal hypoplasia congenita (AHC) is a rare disorder. The X-linked form is related to mutations in the DAX1 (NROB1) gene. Here, we report a newborn who had a novel hemizygous frameshift mutation in DAX1 (c.543delA) and presented with primary adrenal failure that was initially misdiagnosed as congenital adrenal hyperplasia. This report highlights the value of genetic testing for definite diagnosis in children with primary adrenal failure due to abnormal adrenal gland development, providing the possibility both for presymptomatic, and in cases with a sibling with this condition, for prenatal diagnosis. Conflict of interest:None declared.
    Full-text · Article · Jul 2013 · Journal of Clinical Research in Pediatric Endocrinology
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    ABSTRACT: Objectives: To investigate the prevalence of genetic mutations in steroid 5α-reductase-2 (SRD5A2), androgen receptor (AR) and steroidogenic factor-1 (SF-1) in Chinese children with hypospadias, and to also explore the possible underlying molecular mechanisms of this disease. Methods: A total of 52 boys with hypospadias were enrolled. Mutational analyses of the SRD5A2, AR and SF-1 genes were performed by direct sequencing. Results: SRD5A2 gene mutations were found in 13.5% (7/52 cases), including five compound heterozygotic and two homozygotic mutations. One novel heterozygotic SF-1 gene mutation was identified in a patient with perineal hypospadias and cryptorchidism, the patient's mother also had the same mutation. No mutation was found in the AR gene. The clinical manifestations of patients with mutations in SRD5A2 or SF-1 varied. Conclusions: In Chinese patients, SRD5A2 gene mutations were, relatively, frequently associated with hypospadias. The SF-1 gene may be another candidate gene for hypospadias. In contrast, AR gene mutations are not commonly associated with this condition.
    No preview · Article · May 2013 · Journal of pediatric endocrinology & metabolism: JPEM
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    ABSTRACT: Abstract We report the case of a 12-year-old boy with a de novo mutation in the DAX1 gene (for dosage-sensitive sex reversal, congenital adrenal hypoplasia critical region on the X chromosome, gene 1; also called NROB1). He was born at term, Addison's disease was diagnosed at 8 years with a salt-wasting syndrome, and then hydrocortisone substitution was taken; the child continued to develop normally. A reoccurrence of salt-wasting syndrome usually happened after an episode of an abrupt withdrawal of hydrocortisone substitution. Because of adrenal insufficiency without hypogonadotropic hypogonadism, he came to the clinic at 12 years of age and hypoplasia of adrenal glands was found by MRI scans. We proposed the diagnosis of congenital adrenal hypoplasia in this patient and identified a hemizygous mutation (c.999_1000insCTCA, p.Leu335ThrfsX389) in exon 1 of the DAX1 gene. To our knowledge, it is a de novo mutation that leads to a frame-shift, a premature stop codon. In conclusion, it is very important to identify mutation in the DAX1 gene for a boy with adrenal insufficiency of unknown etiology.
    No preview · Article · Nov 2013 · Journal of pediatric endocrinology & metabolism: JPEM
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