Molecular and clinical characterization of Korean patients with congenital lipoid adrenal hyperplasia.
Journal - Journal of pediatric endocrinology & metabolism : JPEM (ENGLAND )
Congenital lipoid adrenal hyperplasia (CLAH) is a rare autosomal recessive disorder of steroid biosynthesis, caused by a molecular defect in the steroidogenic acute regulatory protein (StAR). Patients with CLAH usually manifest severe salt wasting, hypovolemia, enlargement of the adrenal glands and complete female external genitalia irrespective of the gonadal sex. CLAH seems to be more common in Koreans and Japanese than in other ethnic populations, with a preponderance of the mutation of a glutamine to a stop codon at the 258th amino acid residue (Q258X) in the StAR gene. Clinical findings of five unrelated Korean patients with CLAH and their molecular defects in the StAR gene are described, and the gene frequency of the Q258X mutation in the Korean population is investigated. All patients developed hypovolemic shock due to severe salt wasting in the first three months after birth. All were hyperpigmented, and three of five phenotypic females were genetic males. The basal ACTH level was extremely high in all patients with the minimal concentrations of all adrenal and gonadal steroids. The Q258X mutation was identified in 9 out of 10 alleles, indicating that the genetic defect in the StAR gene of Korean patients with CLAH is highly homogeneous probably due to a founder effect. The carrier frequency of the Q258X mutation in the normal Korean population has been estimated as approximately 1 in 250 with the allele frequency of 1 in 500. However, the confidence limits of the gene frequency for the mutant allele are wide (0.5 to 8.0 among 1,000 alleles). This implies that the carrier frequency could be lower, down to 1/1,000, or higher, up to 16/1,000.
|ISSN : ||0334-018X|
|Mesh Heading : ||Adrenal Hyperplasia, Congenital Female Gene Frequency Humans Infant Infant, Newborn Korea Male Mutation Phosphoproteins Pigmentation Disorders Shock complications genetics genetics etiology etiology|
|Mesh Heading Relevant : ||Lipid Metabolism genetics physiopathology|
Growth hormone deficiency associated with pituitary stalk interruption syndrome.
Journal - Hormone research (SWITZERLAND )
|ISSN : ||0301-0163|
|Mesh Heading : ||Adult Breech Presentation Child Female Human Growth Hormone Humans Male Pituitary Diseases Pregnancy|
|Mesh Heading Relevant : ||deficiency complications|
Prenatal molecular evaluation of six fetuses in four unrelated Korean families with ornithine transcarbamylase deficiency.
Journal - Journal of Korean medical science (KOREA )
Ornithine transcarbamylase (OTC) deficiency, an X-linked inborn error of the urea cycle, leads to the accumulation of ammonia, causing neurologic deficits. Clinical management for the patients with OTC deficiency is frustrating and requires a burdensome medical regimen, since they may have impairment and recurrent episodes of hyperammonemia in spite of intensive care. Therefore, prenatal diagnosis of the affected fetus is important in genetic counselling for the family at high risk. In this study, mutations in the OTC gene of three obligate heterozygotes and a proband have been identified in four unrelated families: R141Q, R320X, H214Y, M205T. Each mutation altered restriction recognition sites; TaqI for R141Q, NlaIII for M205T, RsaI for H214Y, BclI for R320X. Based on their molecular defects, prenatal diagnoses of 6 fetuses including one set of fraternal twins were successfully made at the ninth to eleventh week of gestation by polymerase chain reaction (PCR)-restriction digestion using genomic DNA from chorionic villus sampling (CVS). We predicted the outcome of all fetuses prenatally. Among six, four were females and two were males, which were determined by PCR amplification of the sex determining region of the Y chromosome (SRY) gene. Each carried a wild type allele for the corresponding mutant allele. They were also tested postnatally for the mutations to be unaffected.
|ISSN : ||1011-8934|
|Mesh Heading : ||Amino Acid Metabolism, Inborn Errors Evaluation Studies as Topic Female Fetus Humans Korea Male Mutation Ornithine Carbamoyltransferase Pedigree Pregnancy Prenatal Diagnosis diagnosis embryology enzymology|
|Mesh Heading Relevant : ||enzymology deficiency genetics|
Identification of new mutations in the ornithine transcarbamylase (OTC) gene in Korean families.
Journal - Journal of inherited metabolic disease (NETHERLANDS )
Ornithine transcarbamylase (OTC) deficiency, an X-linked inborn error of the urea cycle, is known to be heterogeneous genetically as well as phenotypically. Molecular defects of Korean patients with OTC deficiency have not been reported. To investigate molecular lesions resulting in OTC deficiency, the OTC genes of unrelated symptomatic or asymptomatic female heterozygotes were amplified exon by exon and analysed by direct sequencing of double-stranded DNA. Three new mutations, two missense and one nonsense, were detected: (1) a C-to-T transition in codon 44 in exon 2 replacing a threonine by an isoleucine (T44I) was found in a late-onset symptomatic female patient but not in her asymptomatic mother; (2) a C-to-T transition in codon 214 creating a new RsaI recognition site in exon 6 and substituting tyrosine for histidine (H214Y) was identified in an asymptomatic female carrier whose son developed acute neonatal onset of OTC deficiency; (3) a C-to-T transition in codon 320 (arginine) abolishing a TaqI recognition site and creating a new BclI site in exon 9 with generation of a stop codon (R320X) leading to premature termination in the enzyme. This nonsense mutation was found in a symptomatic female patient and her asymptomatic mother whose son died of OTC deficiency during the neonatal period. In addition, we found a G-to-A transition in codon 141 in exon 5 causing substitution of glutamine for arginine (R141Q) in a female obligate heterozygote whose previous three sons succumbed to acute neonatal-onset OTC deficiency. This missense mutation has been described previously and is known to eliminate a TaqI recognition site in exon 5.
|ISSN : ||0141-8955|
|Mesh Heading : ||Alleles Amino Acids Base Sequence Cell Line DNA Exons Family Female Heterozygote Humans Infant Infant, Newborn Korea Male Molecular Sequence Data Ornithine Carbamoyltransferase Pedigree Polymerase Chain Reaction Polymorphism, Genetic metabolism analysis isolation & purification deficiency|
|Mesh Heading Relevant : ||Mutation genetics|