Everett W. Lovrien

Translocation(X;Y)(p22.33;p11.2) in XX males: Etiology of male phenotype

SummaryAnalysis of G-banded prometaphase chromosomes from three XX males revealed extra bands on the distal end of one X short arm. These bands were similar both in size and staining properties to the distal Y short arm of their fathers (in the two cases examined) and also to other chromosomally normal males. The extra material on the abnormal X chromosomes was not C-or G-11 positive in the two cases examined, suggesting that the proximal Y long arm was not present.Previous karyotype-phenotype correlations with structurally altered Y chromosomes provided evidence for localization of male determinants on the Y short arm. The present findings in XX males provide support for more precise localization, to bands p11.2→pter of Y short arm.

CG dinucleotide transitions in the factor IX gene account for about half of the point mutations in hemophilia B patients: a Seattle series

SummaryHemophilia B is due to multiple molecular defects in the factor IX gene. Over 80% of mutations are single base substitutions. By amplification and direct sequencing, 51 single base substitutions were found in the transcribed sequence of the factor IX genes of patients from 50 distinct families with hemophilia B. These include 30 mutations in 29 families not previously reported by us; of these, 12 are novel, i.e., not previously published in other series. Of the 51 substitutions in our overall series 23 (45%) occurred as C-to-T or G-to-A transitions at 11 sites within CG dinucleotides. It is estimated that CG transitions occur from one to two orders of magnitude more frequently than mutations in nucleotides that are not within a CG pair. More than one family had identical defects for 6 of the CG mutations. At 4 of these sites, most patients had different haplotypes compatible with distinct mutations. Non-CG-type mutations occurred thoughout the coding regions with only one mutation in more than one family. The latter included 7 families with a 397 Ile-to-Thr defect that all share a rare haplotype, suggesting a common ancestor.

Hemoglobin casper: β 106 (G8) Leu→Pro: A contemporary mutation

Abstract Two unrelated sporadic patients with hemolytic anemia were found to have the same previously undescribed abnormal hemoglobin (β106 Leu → Pro), named for Casper, Wyoming, where the first proband was born. Both were detected because of anemia and splenomegaly associated with intercurrent infections during the first 2 years of life. Progressive anemia and splenomegaly ensued; and both have showed improvement after splenectomy. No abnormal hemoglobin was detected by electrophoresis at pH 8.6 or 6.9. Freshly drawn blood contained slightly increased amounts of methemoglobin and had no gross alteration in heme to globin ratios. Heinz body generation and heat stability tests for an unstable hemoglobin were positive. Oxygen affinity of their whole blood was greater than normal. Acute hemolytic episodes with increased reticulocytosis have occurred both before and after splenectomy as accompaniments of intercurrent infections. The data reported on unstable hemoglobin variants permit a tentative classification according to clinical severity. Contemporary mutations account for the majority of the reported cases with clinical disease.

Mannosidosis In Three Brothers—a Review Of The Literature

Three brothers with mannosidosis were studied, and their clinical and biochemical manifestations are compared with those of 41 cases in the literature. All three boys have psychomotor and growth retardation, characteristic facies, recurrent respiratory infections, sensorineural deafness, craniosynostosis, protuberant abdomens, and thin limbs. Roentgenographic findings of mild dysostosis multiplex, thick calvaria, abnormally contoured vertebrae, coarse trabeculi and thin cortices are consistent with those of reported cases. The lymphocytes of peripheral blood and bone marrow are vacuolated. Alpha-mannosidase deficiency in leukocytes and cultured skin fibroblasts and glycoproteinuria have been documented. The biochemistry of this glycoproteinosis and the pitfalls in diagnosis, such as improper assay conditions of pH and substrate concentration, are discussed. Extrapolation of in vitro and animal model studies suggest that trace metal therapy may be more effective than attempts at enzyme replacement to treat this hereditary storage disease.

Dyschondrosteosis and Madelung's deformity. Report of three kindreds and review of the literature.

Dyschondrosteosis is a syndrome of Madelungs deformity, mesomelia and mild short stature that is transmitted by autosomal dominant inheritance. Most examples of Madelungs deformity are due to Dyschondrosteosis. Three affected kindreds are described, two having radiographically proven male to male transmission. A possible association with mental retardation has been postulated on the basis of its presence in four of eleven affected individuals in three kindreds. Dyschondrosteosis exhibits little functional impairment or cosmetic deformity suggesting that therapy is usually unnecessary.

Diffuse capillary hemangiomas associated with skeletal hypotrophy.

A syndrome of capillary hemangiomas of the lower limbs associated with decreased circumference and length of the limb is reported. Hypotrophy of the limb in this syndrome is slowly progressive and surgery is usually required to achieve limb-length equalization. This syndrome is to be distinguished from the more common Klippel-Trenaunay-Weber syndrome of skeletal hypertrophy associated with multiple hemangiomas.

Alpha-1-antitrypsin protease inhibitor (Pi) phenotypes in Down's syndrome patients and their parents

Alpha‐1‐antitrypsin was examined in the serum from 121 Downs syndrome families. Variant phenotypes (non‐M) were increased in frequency in parents (15 %) and in their affected children (19 %) compared to frequencies of 8–10 % in two control groups (p < 0.001). Variant parental Pi phenotypes were found in 19 mothers and 10 fathers of Downs patients. Parental origin of the extra chromosome 21 was known in 34 families and was maternal in 26 instances. In seven families where parental origin of the extra chromosome was known, a variant Pi phenotype was inherited from the parent contributing the extra chromosome in four families and from the parent not contributing the extra chromosome in three families, indicating that there is no simple correlation between the Pi variant and nondisjunction. The increase in Pi variants in Downs syndrome families was independent of maternal age.