Yen-Yin Chou

Hypophosphatemic rickets associated with epidermal nevus syndrome and giant hairy nevus.

The association of hypophosphatemic rickets and epidermal nevus or giant hairy nevus is rare. We report two patients with hypophosphatemic rickets, one associated with epidermal nevus syndrome and the other with giant hairy nevus, and describe their clinical features and variable response to treatment. The abnormal nevus tissue may have contributed to the pathogenesis of hypophosphatemic rickets. We did not find a PHEX gene mutation in these two patients, and the mechanism for their rickets may be different from that in X-linked hypophosphatemic rickets.

Characterization of p-GaAs by low pressure MOCVD using DEZ as dopant

Abstract Zinc-doped GaAs epilayers grown by low pressure metalorganic chemical vapor deposition (LP-MOCVD) are studied. Triethylgallium (TEG) and arsine (AsH 3 ) are used as Ga and As source, respectively. Diethylzinc (DEZ) is used as p-type dopant. Layers of high crystalline quality can be obtained. The influence of growth parameters such as DEZ mole fraction, growth temperatures and AsH 3 mole fraction on hole concentration are measured and discussed. These results can be explained well by a simple qualitative model. The hole concentration is proportional to the concentration of gallium vacancies. The I – V characteristics of Schottky diodes and p-n junctions are discussed. The ideality factor is about 1.3.

Clinical suppression of precocious puberty with cetrorelix after failed treatment with GnRH agonist in a girl with gonadotrophin-independent precocious puberty

This report presents the case of a 7-year-old girl with gonadotrophin-independent precocious puberty treated with cetrorelix [gonadotrophin-releasing hormone (GnRH) antagonist] after poor response to GnRH agonist therapy was observed in the endocrinology outpatient clinic. Uterine and ovarian morphology returned to within the normal prepubertal range after GnRH antagonist was injected subcutaneously. Vaginal bleeding stopped completely. The effects of GnRH antagonist treatment were comparable to those of GnRH agonist. The potential advantage of GnRH antagonists would be a clinically significant direct effect on the ovary, if it exists, and GnRH antagonists should be available for use in such children.

Russell-Silver Syndrome: Molecular Diagnosis of Maternal Uniparental Disomy of Chromosome 7 Using Methylation-Specific Polymerase chain Reaction Assay and Single Nucleotide polymorphisms Genotyping

Russell-Silver syndrome (RSS) should be suspected in patients with prenatal and postnatal growth retardation. Because there is no clinical feature specific for RSS, molecular analysis is necessary to confirm the diagnosis. Recently, maternal uniparental disomy of chromosome 7 (mUPD7) has been reported in approximately 10% of RSS patients. We describe a 10-year-old Taiwanese RSS girl with prenatal and postnatal growth retardation, relative macrocephaly, a triangular face, frontal bossing, and mild fifth finger clinodactyly. Molecular diagnosis of mUPD7 was confirmed by use of methylation-specific polymerase chain reaction and haplotype analysis with single nucleotide polymorphisms (SNPs) genotyping. Analyzing the methylation status of the PEG1/MEST gene is a cost-effective screening method for mUPD7 molecular diagnosis. However, positive cases should be subsequently confirmed by haplotype analysis using SNPs genotyping or short tandem repeat markers.

Novel PHEX gene mutations in two Taiwanese patients with hypophosphatemic rickets

Hypophosphatemic rickets is a genetic disorder commonly associated with renal phosphate wasting and bone deformities. The PHEX gene (phosphate regulating gene with homologies to endopeptidases on the X chromosome) encodes a 749-amino acid protein that putatively consists of an intracellular, transmembrane, and extracellular domain. PHEX mutations have been observed in 60-80% of hypophosphatemic rickets patients. In this study, we report 2 de novo novel mutations in 2 Taiwanese girls with clinical characteristics of hypophosphatemic rickets. The presenting phenotype of lower extremity deformities and short stature was suggestive of the diagnosis. Primers flanking 22 exons were used to amplify DNA by polymerase chain reaction. The results by direct DNA sequencing of case 1 revealed a C to T transition changing glutamine at codon 224 in exon 6 to a stop codon (Q224X). The result of case 2 showed a 2-base pair deletion (2090delGA) and resulted in a frameshift and premature termination of codon (PTC+19aa). Both mutations presumably result in a truncated protein, leading to loss of function of PHEX. This is the first report of PHEX gene mutation in the Taiwanese population.

Sex-Reversed Acampomelic Campomelic Dysplasia With a Homozygous Deletion Mutation in SOX9 Gene

Campomelic dysplasia (CD) is a rare autosomal dominant skeletal malformation with or without sex reversal. About 10% of cases that present with milder skeletal features are referred to as acampomelic campomelic dysplasia (ACD). CD and ACD are caused by mutations in SOX9. We report a patient of homozygous SOX9 deletion with minimal skeletal anomaly and female external genitalia in the presence of a male karyotype. The mechanisms explaining the homozygous deletion include a de novo mutation followed by gene conversion, uniparental disomy, or somatic crossing over. Our report highlights the possibility of ACD in XY sex-reversed patients with minimal skeletal presentation.

Complex chromosome rearrangement 46,XY, der(9)t(Y;9)(q12;p23) in a girl with sex reversal and mental retardation

Monosomy 9p syndrome, also known as Alfi syndrome, has been described as a contiguous syndrome characterized by mental retardation, developmental delay, and facial dysmorphisms. Males with monosomy 9p often express variable degrees of feminization, although the genitalia of females will be normal. In the present report, we describe a case of ambiguous genitalia and intra-abdominal testicular development, with a derivative chromosome 9 arising from a translocation between 9p23 and Yq heterochromatin. Pathologic examination of the testes showed germ cell hypoplasia of the seminiferous tubules. fluorescence in situ hybridization, spectral karyotyping, and array comparative genomic hybridization were used to characterize the genetic changes.

A novel SRD5A2 mutation in a Taiwanese newborn with ambiguous genitalia

The 5α‐reductase type 2 deficiency is a rare autosomal recessive 46,XY disorder of sex development caused by the mutated 5α‐reductase type 2 (SRD5A2) gene. In this disease, defective conversion of testosterone to dihydrotestosterone leads to variable presentations of male ambiguous genitalia during fetal development. The most crucial clinical decision for the affected individual is proper gender assignment; therefore, a prompt and correct diagnosis is important. In this present study, we report a normal male karyotype manifesting microphallus, bifid scrotum/labia majora with bilateral palpable gonads, and a blind‐ended pseudovagina. The mutation analysis of the SRD5A2 gene revealed one novel C to T transition changing glutamine to a stop codon at codon 71 (p.Q71X) in exon 1 and one known G to A transition changing arginine to glutamine at codon 227 (p.R227Q) in exon 4. The p.Q71X mutation presumably results in a truncated protein, while the p.R227Q mutation is conceived to impair enzyme function and has been reported in patients of East Asian descent. This report demonstrates the essential role of hormonal and molecular studies for genetic counseling and gender assignment in males with pseudovaginal disorder of sex development, and our report helps identify a novel SRD5A2 gene mutation in the Taiwanese population.

A 38.8 kb deletion mutation of the iduronate-2-sulfatase gene in a patient with Hunter syndrome.

Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked lysosomal storage disorder. A novel gross deletion in the iduronate-2-sulfatase (IDS) gene was found in a 6-year-old boy with Hunter syndrome. The phenotype of the patient was severe, including joint stiffness, kyphosis, hepatomegaly, hypertrophic cardiomyopathy, moderate mental retardation, and bilateral hearing loss. The 38.8 kb gross deletion involves exons 1-7, the proximal breakpoints lying in intron 7, at position 1307880 (GenBank NT:019686), and the distal deletion breakpoint was located at position 1346697. The large deletion correlated with the severe phenotype of this Hunter syndrome patient.

Measuring propionyl-CoA carboxylase activity in phytohemagglutinin stimulated lymphocytes using high performance liquid chromatography.

BACKGROUND Propionyl-CoA carboxylase (PCC) is a mitochondrial enzyme involved in the catabolism of several essential amino acids and odd chain fatty acids. Previous PCC assays have involved either a radiometric assay or have required mitochondria isolation and/or enzyme purification. METHODS We developed an enzymatic method to analyze PCC activity in phytohemagglutinin (PHA) stimulated lymphocytes that involves high performance liquid chromatography. RESULTS The method shows good linearity and sensitivity. PCC activity was unaffected even when lymphocytes were isolated and PHA stimulated after a whole blood sample had been stored at 4°C for 5days. This indicates that this method is suitable for analyzing samples from distant medical centers. The PCC activity of patients with propionic acidemia was found to be much lower than that of normal individuals and carriers. However, this PCC assay is significantly affected by the red blood cell contamination. In conclusion, this is a reliable method for performing PCC assays and only requires 0.5 to 1.0ml of whole blood from newborns. CONCLUSIONS The PCC assay established in this study is useful for the confirmation of PA in individuals, and prenatal diagnosis and genetic counseling for the affected families.