Polyuria and polydipsia in a young child: diagnostic considerations and identification of novel mutation causing familial neurohypophyseal diabetes insipidus.

A 3-year 5-month-old boy was seen for second opinion regarding polydipsia and polyuria. Previously, a diagnosis of primary polydipsia was made after normal urine concentration after overnight water deprivation testing. The boy's father, paternal grandfather, and paternal aunt had diabetes insipidus treated with desmopressin acetate.

Molecular testing for Fragile X Syndrome: lessons learned from 119,232 tests performed in a clinical laboratory.

Purpose: To examine the data from over 119,000 Fragile X Syndrome tests and 307 prenatal tests to detect unsuspected findings and obtain clinical data when indicated to optimize genetic counseling.

Methods: A proprietary database containing 119,232 consecutive postnatal and 307 prenatal FXS tests performed between November 2, 1992 and June 1, 2006 was queried.

Results: The distribution of normal FMR1 alleles was a bimodal distribution with a major peak at 30 repeats and a minor peak at 21 repeats.

Hyponatremia resulting from arginine vasopressin receptor 2 gene mutation.

Chronic hyponatremia, unless associated with extracellular fluid volume expansion, is an infrequent electrolyte imbalance in pediatrics. We report an infant with chronic hyponatremia suggestive of a syndrome of inappropriate secretion of antidiuretic hormone (SIADH), in the absence of ADH secretion. A mutation was found in the same codon of the gene that results in a loss-of- function of arginine vasopressin receptor 2 (AVPR2) observed in congenital nephrogenic diabetes insipidus.

Identification of four gene variants associated with myocardial infarction.

Family history is a major risk factor for myocardial infarction (MI). However, known gene variants associated with MI cannot fully explain the genetic component of MI risk. We hypothesized that a gene-centric association study that was not limited to candidate genes could identify novel genetic associations with MI.

Nephrogenic syndrome of inappropriate antidiuresis.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, yet who had undetectable arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-function mutations in the V2 vasopressin receptor (V2R).

Nine novel germline gene variants in the RET proto-oncogene identified in twelve unrelated cases.

We report nine novel DNA alterations in the RET proto-oncogene in 12 unrelated cases identified by DNA sequencing of exons 10 and 11 of the gene. The novel variants K666E, IVS9-11G-->A, D631V in cis with H665Q, D631E (with C634Y), E623K (in trans with C618S), 616delGAG (in trans with C609Y), Y606C, C630R, and R635-T636insELCR;T636P were detected in patients with various clinical presentations ranging from thyroid goiter, medullary thyroid carcinoma, and pheochromocytoma to classic multiple endocrine neoplasia type 2A. When novel DNA alterations are found, extended family studies can be helpful in determining the clinical significance of such findings.

Validation and clinical application of a locus-specific polymerase chain reaction- and minisequencing-based assay for congenital adrenal hyperplasia (21-hydroxylase deficiency).

Congenital adrenal hyperplasia is an autosomal recessive disorder caused by defective adrenal steroid biosynthesis, resulting in reduced glucocorticoid and increased androgen production. The majority of cases are due to inactivation of the 21-hydroxylase gene (CYP21A2), most commonly caused by genomic rearrangements with the adjacent, highly homologous pseudogene CYP21A. The most common deletions and gene conversion events have been defined and are typically detected by Southern hybridization detection of CYP21 rearrangements and/or polymerase chain reaction (PCR).