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1.
J Clin Endocrinol Metab ; 84(11): 4111-7, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10566658

ABSTRACT

Pseudovitamin D deficiency rickets (PDDR) is an autosomal recessive disorder caused by defect in the activation of vitamin D. We recently isolated 25-hydroxyvitamin D3 1alpha-hydroxylase gene and identified four homozygous inactivating missense mutations in this gene by analysis of four typical cases of PDDR. This disease shows some phenotypic variation, and it has been suspected that patients with mild phenotypes have mutations that do not totally abolish the enzyme activity. To investigate the molecular defects associated with the phenotypic variation, we analyzed six additional unrelated PDDR patients: one with mild and five with typical clinical manifestation. By sequence analysis, all six patients were proven to have mutations in both alleles. The mutations varied, and we identified four novel missense mutations, a nonsense mutation, and a splicing mutation for the first time. The patient with mild clinical symptoms was compound heterozygous for T321R and a splicing mutation. The splice site mutation caused intron retention. Enzyme activity of the T321R mutant was analyzed by overexpressing the mutant 1alpha-hydroxylase in Escherichia coli cells to detect the subtle residual enzyme activity. No residual enzyme activity was detected in T321R mutant or in the other mutants. These results indicate that all of the patients, including those of mild phenotype, are caused by 1alpha-hydroxylase gene mutations that totally abolish the enzyme activity.


Subject(s)
25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism , Mutation , Rickets/genetics , Vitamin D Deficiency/genetics , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics , Alleles , DNA Mutational Analysis , Female , Humans , Infant , Male , Mutation, Missense , Pedigree , Phenotype , RNA Splicing , Rickets/enzymology
2.
Genes Chromosomes Cancer ; 25(1): 40-5, 1999 May.
Article in English | MEDLINE | ID: mdl-10221338

ABSTRACT

This study reports on Y chromosomal genotypes of three patients with gonadoblastoma and one patient with gonadoblastoma and mixed germ cell tumor. Molecular analysis for 35 Y chromosomal loci was performed for DNA samples taken from peripheral leukocytes and lymphoblastoid cell lines, showing that the four patients shared the region between DYS267 at interval 4A and DYF50S1 at interval 6D, with the exception of the region around DYS202 at interval 5K. In the patient with gonadoblastoma and mixed germ cell tumor, Y chromosomal material was preserved in the gonadoblastoma but was lost from the mixed germ cell tumor. The results, in conjunction with previous reports, suggest that GBY (gonadoblastoma locus on the Y chromosome) may be located to a roughly 5-Mb pericentromeric region between DYS267 at interval 4A and DYS270 at interval 5A. The presence of Y chromosomal material in gonadoblastoma is consistent with GBY being involved in the development of gonadoblastoma, and the absence of Y chromosomal material in mixed germ cell tumor would be explained as a consequence of Y chromosomal loss from rapidly proliferating gonadal cancer cells.


Subject(s)
Germinoma/genetics , Gonadoblastoma/genetics , Ovarian Neoplasms/genetics , Y Chromosome/genetics , Adolescent , Blotting, Southern , Child , DNA, Neoplasm/analysis , Female , Genetic Markers , Genotype , Humans , In Situ Hybridization, Fluorescence , Infant , Polymerase Chain Reaction
4.
Hum Genet ; 97(4): 435-7, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8834238

ABSTRACT

We have analyzed two unrelated Japanese patients with carbonic anhydrase II deficiency born to consanguineous parents. We have identified the same mutation as that reported to be homozygous in a Belgian family and compound heterozygous in an American family. It comprises to C-to-T transition that results in the amino acid substitution of Tyr (TAT) for His (CAT) at position 107. This point mutation creates an AccI site that can be conveniently screened by the polymerase chain reaction/restriction fragment length polymorphism method using a restriction enzyme for gene tracking. Our patients exhibit severe mental retardation, not seen in the Belgian and American patients.


Subject(s)
Carbonic Anhydrases/deficiency , Carbonic Anhydrases/genetics , Central Nervous System Diseases/genetics , Point Mutation , Exons/genetics , Humans , Japan , Polymerase Chain Reaction
6.
Kurume Med J ; 41(3): 155-9, 1994.
Article in English | MEDLINE | ID: mdl-7853832

ABSTRACT

We report the case of a 15-year-old girl with bilateral gonadoblastoma and 45,X/46,X,+mar karyotype. She was short but had no other stigmata of Turner syndrome. Her genitalia were completely of the female type until she began to show signs of masculinization at age 13 years. She had breasts of Tanner stage 4, primary amenorrhea, clitoromegaly, hirsutism and low voice. Plasma testosterone level was elevated and returned to normal after the successful removal of the bilateral gonadoblastoma. Her karyotype was 45,X/46,X,+mar and it was proved that the marker chromosome was derived from the short arm of the Y chromosome by Southern blot analysis with a Y chromosome specific probe, pDP1007. Even when there are no stigmata of Turner syndrome or signs of intrauterine virilization, the possibility of gonadoblastoma should not be ruled out in girls who show postnatal virilization.


Subject(s)
Gonadoblastoma/complications , Ovarian Neoplasms/complications , Puberty , Turner Syndrome/genetics , Virilism/etiology , Adolescent , Female , Gonadoblastoma/genetics , Humans , Karyotyping , Ovarian Neoplasms/genetics , Virilism/genetics
7.
J Child Neurol ; 8(4): 412-5, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8228041

ABSTRACT

A 2-year-old girl with Turner syndrome was admitted with left hemiplegia and left facial palsy. Serial cranial computed tomographic scan demonstrated multiple cerebral infarctions in the right putamen and right medial cortical areas. Single photon emission computed tomographic scan revealed hypoperfusion from the right frontal to the right temporal area. Right carotid angiography showed narrowing and occlusion of the right internal carotid artery at the sphenoidal portion. Collateral circulation was not detected between the external and internal carotid arteries. Left carotid angiography revealed that the left anterior artery was narrow, and that the left internal carotid artery provided blood to the right internal carotid artery through the anterior communicating artery. These findings suggested that the cerebrovascular abnormality might be due to congenital hypoplasia of arteries in this patient. The unusual combination of cerebral infarction and Turner syndrome was reported.


Subject(s)
Arterial Occlusive Diseases/physiopathology , Carotid Artery, Internal/physiopathology , Turner Syndrome/physiopathology , Arterial Occlusive Diseases/complications , Arterial Occlusive Diseases/diagnosis , Brain/blood supply , Brain/diagnostic imaging , Brain/physiopathology , Cerebral Angiography , Cerebral Infarction/complications , Cerebral Infarction/diagnosis , Cerebral Infarction/physiopathology , Child, Preschool , Chromosome Aberrations , Chromosome Disorders , Cognition Disorders/etiology , Electroencephalography , Female , Humans , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Turner Syndrome/complications , Turner Syndrome/genetics
8.
J Pediatr Gastroenterol Nutr ; 12(3): 383-7, 1991 Apr.
Article in English | MEDLINE | ID: mdl-2072233

ABSTRACT

We report a premature infant with severe hypoglycemia (serum glucose: 6 mg/dl) and cholestasis (serum total bile acids: 211.55 mumol/L) caused by hypoplasia of the interlobular bile ducts. This patient had developed intracranial hemorrhage and sepsis while undergoing treatment for hypoglycemia. As a result of endocrine evaluation, we made a diagnosis of idiopathic panhypopituitarism, congenital absence or hypoplasia of the pituitary gland. Moreover, we found abnormal bile acid profiles: The ratio of cholic acid to chenodeoxycholic acid was abnormally low in serum (0.04) and in biliary bile (0.33). However, 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid and bile alcohols were not detected. We therefore suspected that the severe cholestasis and abnormal bile acid profiles in the serum and biliary bile in this patient were related to physiologic immaturity of the enterohepatic circulation of bile acids and immaturity of hepatic 12 alpha-hydroxylation.


Subject(s)
Bile/chemistry , Chenodeoxycholic Acid/analysis , Cholestasis/complications , Cholic Acids/analysis , Hypoglycemia/complications , Adult , Bile Duct Diseases/complications , Chenodeoxycholic Acid/metabolism , Cholestasis/metabolism , Cholestasis/physiopathology , Cholic Acid , Cholic Acids/blood , Enterohepatic Circulation , Female , Humans , Hypoglycemia/metabolism , Hypoglycemia/physiopathology , Infant, Newborn , Male
9.
Eur J Pediatr ; 150(1): 30-3, 1990 Nov.
Article in English | MEDLINE | ID: mdl-2079074

ABSTRACT

Hypothalamic pituitary function and growth hormone releasing hormone (GHRH) loading tests in two children with septo-optic dysplasia (SOD) revealed isolated GH deficiency in one and deficiencies of growth hormone, adrenocorticotropic hormone and antidiuretic hormone in the other. Secretion of GH was elicited in the first patient by single i.v. bolus administration of GHRH and after repetitive i.v. infusions of GHRH in the second. With these results we confirmed that the hypopituitarism in our patients with SOD was of hypothalamic origin. Both patients also had infantile spasms.


Subject(s)
Brain/abnormalities , Growth Hormone/deficiency , Hypopituitarism/etiology , Hypothalamus/physiopathology , Adrenal Glands/physiology , Child, Preschool , Female , Growth Hormone-Releasing Hormone/physiology , Humans , Hypopituitarism/physiopathology , Infant , Male , Optic Nerve/abnormalities , Thyroid Gland/physiology
15.
Acta Pathol Jpn ; 32(3): 505-11, 1982 May.
Article in English | MEDLINE | ID: mdl-7102311

ABSTRACT

This report described the morphological characteristics of seven cases of asplenia syndrome and three of polysplenia syndrome. Each syndrome has been characterized by a tendency for symmetric development of normally asymmetric organs, with varying degrees of cardiovascular anomalies. These latter anomalies are usually present in asplenia syndrome to a greater extent than in polysplenia syndrome. While, as observed in our material, the conotruncal anomalies were present more commonly in cases with asplenia, and absence of inferior vena cava with azygos continuation was seen specifically in all the cases with polysplenia. This evidence implied the presence of some pathogenetic distinction between the two syndromes.


Subject(s)
Heart Defects, Congenital/complications , Spleen/abnormalities , Abnormalities, Multiple , Azygos Vein/abnormalities , Blood Vessels/abnormalities , Digestive System Abnormalities , Female , Humans , Infant , Infant, Newborn , Liver/abnormalities , Lung/abnormalities , Male , Syndrome , Vena Cava, Inferior/abnormalities
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