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Y E Hsia

Publications and source records attributed to Y E Hsia.

At least 19 recordsLinked to original sources
PubMed1995

Von Hippel-Lindau syndrome.

After a decade of intensive clinical and molecular genetic efforts the von Hippel-Lindau (VHL) gene was cloned in 1993. The open reading frame encodes the putative protein of 284 amino acids. A large number of different mutations have been identified so far, including single base mutations, deletions, rearrangements and more complex mutations. So far, in about 75% of the VHL families germline mutations were detected. Geno-phenotypic comparison has revealed specific mutations with distinct manifestation patterns. Not all of the 6 classical lesions (hemangioblastoma of the CNS, retinal angiomatosis, pancreatic cysts, renal cysts and carcinoma, pheochromocytoma and epididymal cystadenoma) are present in VHL families. Pedigrees with pheochromocytoma but without renal cancer in general have point mutations. These recent results provide insight in the pathogenesis of a multiorgan cancer susceptibility tumor suppressor gene and allow determination of carrier status.

Brain↗
PubMed1992

Glucose-6-phosphate dehydrogenase variants in Hawaii.

Sequence analysis has been performed on the DNA of 13 glucose-6-phosphate dehydrogenase (G6PD) deficient males from Hawaii, 6 of Filipino, 6 of Laotian, and 1 of Chinese extraction. Four different mutations were found: A-->T at cDNA nt 835, G-->A at nt 871, C-->T at nt 1360, and G-->A at nt 1388. The mutations at nt 835 and nt 1360 have not been described previously, and the latter, in particular, appears to be relatively common. The nt 1360 mutation changes the same codon as is altered in a previously described mutation, G6PD Andalus.

China↗
PubMed1991

Hereditary anemias in Hawaii. 1987.

The differential diagnosis of microcytic anemias in Hawaii presents special problems because of the hereditary anemias prevalent in its large Asian subpopulations. Both the alpha- and beta-thalassemias are important because of morbidity and mortality. Heterozygous carriers for either type mimic iron deficiency, which may lead to inappropriate work-up or treatment. The thalassemias and hemoglobin (Hb) variants are all benign in heterozygotes, but if a couple are both heterozygous for the same or for incompatible variants, their children have 25% risk of inheriting a serious anemia. These can be prevented by detecting the heterozygotes, and by offering genetic counseling and fetal testing to couples at risk of having severely affected children. Early detection is also possible by the screening of newborns. Fetal diagnosis, or early detection and treatment, can greatly reduce the consequences of these anemias. Screening and prevention will cost far less than the cost of care for affected patients.

Anemia↗
PubMed1990

Prenatal findings in Brachmann-de Lange syndrome.

Brachmann-de Lange syndrome is a congenital disorder of uncertain cause characterized by severe mental retardation, small stature, microbrachycephaly, hirsutism, limb deformities, and characteristic facies. Although more than 300 neonatal cases have been reported, a lack of specific fetal markers has precluded successful antepartum diagnosis. We describe a case of Brachmann-de Lange syndrome identified at 15 weeks' gestation by a low maternal serum alpha-fetoprotein (MSAFP) value. Sonography revealed a fetus with a posterior nuchal cystic hygroma and early-onset symmetrical intrauterine growth retardation (IUGR). The fetal karyotype was 46,XX, but the infant fulfilled the phenotypic criteria of the Brachmann-de Lange syndrome at delivery. The triad of an abnormally low MSAFP value, early-onset symmetrical IUGR, and characteristic ultrasound findings during the second trimester of pregnancy may define adequate criteria for prenatal diagnosis of Brachmann-de Lange syndrome.

Adult↗
PubMed1989

Molecular screening for haemoglobin constant spring.

Haemoglobin H/Constant Spring is an important cause of severe haemoglobin H disease, but the Constant Spring protein is difficult to detect by electrophoresis. A technique for allele specific polymerase chain amplification of the 3'-end of the alpha 2 globin gene improved detection of the alpha cs alpha haemoglobin variant in DNA samples by slot-blot hybridisation. The alpha cs alpha mutation was confirmed in subjects that had been previously diagnosed by haemoglobin electrophoresis, and it was also detected in patients who were negative by protein electrophoresis. 10 of 103 unrelated Laotians with HbE were alpha cs alpha heterozygotes. Of these, 3 were negative to the normal probe because they had -alpha 3.7/alpha cs alpha with a single alpha globin deletion. 5 samples did not amplify or hybridise to either probe because they had deletions of both alpha 2 globin regions. The gene frequency for alpha cs alpha is about 0.05 for Laotians. This technique, which is highly specific and sensitive for rapid detection of the alpha cs alpha mutation, is suitable for clinical diagnoses and population studies. The true incidence of alpha cs alpha may prove to be greater than previously suspected from protein electrophoresis.

Alpha-Globulins↗
PubMed1989

von Hippel-Lindau disease affecting 43 members of a single kindred.

We present a 6-generation kindred of over 221 members, 43 of whom were affected with von Hippel-Lindau (vHL) disease. Through a simple screening protocol, we diagnosed vHL retrospectively in 15 cases, and for the first time in 28, 11 of whom were presymptomatic. We found many complications of vHL in previously diagnosed relatives and in new cases. This study has demonstrated the utility and benefit of preventive surveillance in those known to have vHL, and of presymptomatic screening for affected relatives in families with vHL. The features of vHL were reviewed in our 43 cases and 511 cases from the medical literature. The patterns, frequencies, and ages of onset for each lesion were compared. Renal malignancies caused almost as much mortality in vHL as CNS malignancies. This family was exceptional for absence of pheochromocytoma and erythrocythemia, for more renal and pancreatic cysts and malignancies, and for slightly fewer eye or CNS lesions. Bilateral renal adenocarcinomata were found presymptomatically in five young subjects, who had bilateral nephrectomy and hemodialysis. Three survived long-term after renal transplants. Five relatives had pancreatic malignancies, which are definite although uncommon manifestations of vHL. Recommendations are made for family screening, which was economical and effective. Bayesian calculations help to predict risks for genetic counseling. The molecular basis of vHL may soon be found, since it has been linked to DNA markers on the short arm of chromosome 3.

Adolescent↗
PubMed1989

The types of hemoglobins and globin chains in hydrops fetalis.

Details are presented of analyses of hemoglobins in blood samples from four newborn babies with hydrops fetalis using reversed phase and anion exchange high performance liquid chromatographic methodology. Three were homozygous for the alpha-thalassemia-1 (SEA) deletion, and one was a compound heterozygote for the same deletion and the larger alpha-thalassemia-1 (Fil) deletion. All four babies had beta, G gamma, A gamma, and zeta chains; these chains were present in Hb Bart's or gamma 4, Hb Portland-I (zeta 2 gamma 2), and Hb Portland-II (zeta 2 beta 2). Hb H (beta 4) could not be detected. The level of zeta was directly related to the level of beta and, thus, the fetal age. A lower level of zeta chain was present in the baby with the compound heterozygosity because the large deletion (Fil) on one chromosome included the zeta and psi zeta genes. Circulating red cells, i.e. reticulocytes and nucleated red cells, were unable to synthesize zeta chains, indicating that this capability must have ceased a few months prior to birth. Quantitative data obtained by chromatographic procedures were greatly influenced by the condition of the blood sample and the way it was stored. Hb Portland-II (zeta 2 beta 2) and Hb Bart's (gamma 4) are rather unstable when a red cell lysate is stored at 4 degrees C; this is in contrast to Hb Portland-I (zeta 2 gamma 2) which appears to be stable. Samples can be stored as washed red cells or red cell lysates at -70 degrees C.

Blood Preservation↗
PubMed1988

The different types of alpha-thalassemia: practical and genetic aspects.

From May 1985 to October 1987, 1,564 Southeast Asians living in Hawaii were screened for hereditary anemias. Microcytosis was determined by electronic red cell indices and morphology; iron deficiency was ruled out by normal red cell distribution width and normal protoporphyrin levels; Hb E was determined by electrophoresis; beta-thalassemia (thal) heterozygotes were identified by raised Hb A2 on column chromatography. alpha-Thalassemia heterozygotes were diagnosed by exclusion. Family studies helped identify or confirm diagnoses, especially for the alpha-thal-2 heterozygotes (-alpha/alpha alpha) and homozygotes (-alpha/-alpha). Provisional diagnoses are being checked by DNA analyses. Iron deficiency prevented detection of possibly coexisting alpha-thalassemias in 97 individuals. Technical problems included the obscuring of standard criteria for recognizing the alpha-thal variants by the presence of Hb E or beta-thal. In such cases, alpha-thal could only be detected by family studies or DNA analyses. Problems with hemoglobin (Hb) electrophoresis included Hb H migrating beyond the edge of the strip if incubation was not closely monitored, and difficulty in detecting the small amounts of unstable Hb Constant Spring. DNA analyses also had limitations, since the nondeletion alpha-thalassemias would not be detected by routine Southern blotting. DNA analyses suggested that about 50% of presumed alpha-thalassemias were alpha-thal-2 (-alpha/alpha alpha) variants, and a corresponding number of alpha-thal-2 variants were among the apparent normals. Gene frequencies in the unselected Lao subjects were approximately 0.2 for Hb E, at least 0.1 for (-alpha), usually a rightward (alpha -3.7) type, 0.04 for (-), and 0.01 for a beta-thal. Multistep screening for the alpha- and beta-thalassemias was an effective and efficient strategy.

Asia, Southeastern↗
PubMed1988

Alpha-thalassemia screening reveals quadruple zeta-globin genes in a Laotian family.

In screening families for alpha-thalassemia (thal) by the Southern blot technique, several Laotian families were found which had anomalous zeta-globin haplotypes. The zeta-globin genes encode alpha-like embryonic hemoglobin subunits in the alpha-globin multigene complex on chromosome 16. There are normally two zeta-globin genes in this cluster: 5' zeta 2 and 3' psi zeta 1. In our study, six individuals in three families had triple zeta-globin genes. Another family revealed a novel quadruple zeta-globin arrangement. Two aberrant fragments were seen in Eco R1, Bam H1, Bgl II and Hind III digests using a zeta-globin gene probe. These anomalous bands were in the integral 10 kb range consistent with duplication of the zeta-globin region. This haplotype interpretation was confirmed by Southern blot analyses using double digestions hybridized to a cDNA zeta-gene probe, and Pvu II digests probed with a 5'-psi zeta 1 intergenic fragment. Proposed mechanisms of recombination and implications of this novel arrangement are discussed.

Blotting, Southern↗
PubMed1988

Thalassemia heterozygotes in Hawaii: ethnic attitudes toward screening and prenatal diagnosis.

The attitudes toward screening and prenatal diagnosis for the hemoglobinopathies Hb E and alpha-thalassemia, prevalent in Southeast Asia, it were studied in Southeast Asians living in Hawaii. Since May 1985, one Laotian and two Filipino Outreach Workers were trained to make home visits to educate and recruit prospective subjects for a federally-funded thalassemia screening project. Volunteers over age 18 were interviewed to assess their comprehension about thalassemia and their attitudes toward screening, family planning, and prenatal diagnosis using structured questionnaires to measure subjective responses. Prenatal diagnosis was explained to all subjects using simple brochures in Laotian and in three Filipino dialects. Culturally oriented genetic counceling was offered to all heterozygotes, emphasizing that their status was common and benign. By July 1987, 597 adult participants had been interviewed; 262 were male, 335 female (65 pregnant); 250 were Laotian, 221 Filipino, 90 Chinese, and 36 of other races. Among female interviewees, 268 said they would want prenatal diagnosis and 196 said they would abort an affected fetus. Most interviewees, especially those who were pregnant, were in favor of: 1) public education about screening, 2) having relatives tested, and 3) prenatal diagnosis when indicated. These attitudes seemed to be influenced by Western culture and religious constraints. Comprehension of genetic concepts correlated closely with education. Ten pregnancies occurred in 16 couples where both partners were heterozygous for a thalassemia (thal) (at least two non-referred couples had homozygous alpha-thal-1 fetuses during this time). Five had amniocentesis for risk of alpha-thal homozygosity, two for risk of beta-thal homozygosity, two miscarried, and one was referred too late for fetal testing. After amniocentesis, one couple declined termination for a fetus with Hb E/beta-thal, and was sceptical of the results when their infant seemed normal at birth; one couple kept a homozygous beta-thal fetus, possibly modified by alpha-gene deletions.

Abortion, Eugenic↗
PubMed1984

Segregation and linkage analyses of von Hippel Lindau disease among 220 descendants from one kindred.

Von Hippel Lindau disease (vHL), an autosomal dominant precancerous condition, had segregated in a large kindred. Fourteen relatives were known to have been affected; record reviews disclosed features of vHL in 15 previously undiagnosed relatives; presymptomatic evaluations detected vHL in 13 additional members of this kindred. Altogether, among 220 descendants of an ancestral couple, 41 had vHL. We screened for HLA haplotypes and for polymorphic gene markers at 31 loci in 102 direct descendants and 16 spouses from this kindred, including 23 with vHL. Linkage analyses failed to reveal a significant lod score with any locus tested, or any HLA linkage disequilibrium. Expression of vHL among the affected relatives was compared with 384 other reported cases of vHL. The age of onset, tissue involvement, and life expectancy in this family were similar to the other reported cases. The sigmoid age-of-onset distribution for vHL most closely matched a square-foot transformation (mean = 26.2(-2) years; variance = 1.224).

Adolescent↗