Wayne H. Finley

The primary erythermalgia-susceptibility gene is located on chromosome 2q31-32.

Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm, and painful hands and/or feet. The symptoms are generally refractory to treatment and persist throughout life. Five kindreds with multiple cases of primary erythermalgia were identified, and the largest was subjected to a genomewide search. We detected strong evidence for linkage of the primary erythermalgia locus to markers from chromosome 2q. The highest LOD score (Z) was obtained with D2S2330 (Z(max) = 6.51). Analysis of recombination events identified D2S2370 and D2S1776 as flanking markers, on chromosome 2q31-32. This defines a critical interval of 7.94 cM that harbors the primary erythermalgia gene. Affected members within the additional families also shared a common haplotype on chromosome 2q31-32, supporting our linkage results. Identification of the primary erythermalgia gene will allow a better clinical classification of this pleomorphic group of disorders.

Nutrient Levels in Amniotic Fluid from Women with Normal and Neural Tube Defect Pregnancies

We analyzed nutrient levels in amniotic fluid obtained during the second trimester of normal, uncomplicated pregnancies from 221 women who delivered apparently healthy infants and from 8 with neural tube defect (NTD) pregnancies. Folate was measured by microbiological assay, vitamin B12 by a radiobinding method, and zinc, copper and iron by atomic absorption spectrophotometry. We found that the mean amniotic fluid nutrient levels of normal pregnancies were 24.7 nmol/l for folate, 600 pmol/l for vitamin B12, and 1.7, 1.9, and 9.0 mumol/l for zinc, copper and iron, respectively. Amniotic fluid folate, zinc, copper and iron levels of NTD pregnancies were similar to those found during normal pregnancy, however, vitamin B12 levels were markedly lower than those of normal pregnancies.

Synthesis and properties of a fluorescent derivative of phosphatidylcholine

Abstract 1-acyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazole)-aminocaproyl phosphatidyl choline, (NBD-PC) was prepared by alkylation of ϵ-amino caproic acid with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-C1), followed by esterification of lysophosphatidylcholine. The compound was purified by silicic acid chromatography, and exhibited a single spot on thin layer chromatography using acidic, basic and neutral solvent systems, when visualized by UV, molybdate spray, primuline, or charring. The UV-visible absorption spectrum, and the uncorrected fluorescence excitation spectrum of NBD-PC in absolute ethanol showed maxima at approximately 340 and 460 nm, while the fluorescence emission spectrum showed a single peak at 525 nm. Fluorescence intensity and emission maximum wavelength of NBD-PC are strongly dependent on solvent dielectric constant, and the relative fluorescent intensity of NBD-PC in absolute ethanol is directly proportional to its concentration from 1 ng/ml to approximately 3 μg/ml. Incorporation of NBD-PC into membranes of human lymphocytes cultures in the presence or absence of phytohemagglutinin (PHA) resulted in a marked increase in the relative fluorescent intensity of the bound fluorochrome, and a 15 nm blue shift in its emission maximum wavelength. Fluorescence titration data indicate that the unstimulated lymphocytes bound 912 pmoles NBD-PC/mg protein with an association constant of 3.45 × 10 7 M, while the PHA stimulated cells bound 1200 pmoles NBD-PC/mg protein with an association constant of 2.82 × 10 7 M. The temperature dependence of the fluorescent intensity of NBD-PC incorporated in control, and PHA stimulated lymphocytes showed discontinuities at 15 and 24 °C respectively. Fluorescence polarization of NBD-PC incorporated in the membranes of stimulated lymphocytes was greater than the polarization of the fluorochrome in non-stimulated cells, suggesting that the plasma membranes of PHA stimulated lymphocytes contain regions of higher microviscosity.

Terminal deletion of the long arm of chromosome 4 in a mother and two sons.

Deletion of chromosome 4q31→pter has been characterized as a distinctive malformation syndrome. We report a mother and two sons with deletion of the long arm (q) of chromosome 4 del(4)(q34.2).

Translocation (6;9)(p23;q34) in Acute Nonlymphocytic Leukemia: Three New Cases

Several recent reports have described cases of acute nonlymphocytic leukemia with a unique chromosome translocation, t(6;9)(p23;q34). We have studied three additional patients who have acute nonlymphocytic leukemia and t(6;9)(p23;q34). Our findings provide additional support for the suggestion that this translocation is yet another distinct cytogenetic abnormality associated with myeloproliferative disorders.

Decreased levels of amniotic fluid α-fetoprotein associated with Down syndrome

Abstract Low maternal serum α-fetoprotein levels have been associated with fetal aneuploidies. Amniotic fluid α-fetoprotein levels have been reported to be low with Down syndrome (trisomy 21) but not with other fetal trisomies. We compared the amniotic fluid α-fetoprotein levels from 25 cases of autosomal trisomy (18 of trisomy 21, four of trisomy 13, three of trisomy 18) diagnosed by midtrimester fetal cytogenetic studies with those from matched, cytogenetically normal pregnancies. With these normal pregnancies used as controls, statistical analyses were performed on the data for all the trisomic fetuses, on the data for trisomy 21 only, and on the data for trisomies 13 and 18 combined. Amniotic fluid α-fetoprotein levels were significantly lower in the 25 trisomic cases compared with controls, 0.77 ± 0.34 versus 1.03 ± 0.34 mg/dl (p 0.40). These findings suggest that the low maternal serum levels of α-fetoprotein reported in cases of Down syndrome may be related to reduced amniotic fluid concentrations. However, the reduced maternal serum α-fetoprotein levels reportedly associated with trisomies 13 and 18 do not seem to be explained by low amniotic fluid concentrations.

Fetal loss and familial chromosome I translocations

A structural abnormality of chromosome No. 1 was found in two families who had a history of repeated abortions. The propositus in Family H was a low birth weight, malformed infant who had a partial trisomy of 1q. His mother and a sibling were balanced carriers of a t(1;4) (q25;q35). In family B, the 29‐year‐old phenotypically normal propositus and his mother were found to be balanced carriers of a t(1;12) (p13;q24). It is suggested that the fetal wastage in both families was related to the abnormal karyotypes of the parents. These two families also provide an opportunity to further understand the effect of an abnormality of chromosome number 1 on phenotype.

A complex chromosome rearrangement resulting in trisomy 15q22→qter

A black infant with malformations was found to have trisomy 15q22→qter. The mother had a complex chromosomal rearrangement involving three chromosomes (5, 13, and 15). A comparison with previously published cases of trisomy for distal 15q suggests a pattern of clinical findings including retardation in growth and development, microcephaly, asymmetrical facies, prominent occiput, antimongoloid slant of the palpebral fissures, micrognathia, prominent nose, and congenital heart disease.

Relationship between amniotic fluid and maternal blood nutrient levels

To study the relationships between amniotic fluid and maternal blood nutrient concentrations, we obtained amniotic fluid and blood samples simultaneously from 76 pregnant women at around 17 weeks gestation. Folate and vitamin B-12 levels were measured by microbiological assay and radioassay, respectively, and zinc, copper and iron levels by atomic absorption spectrophotometry. Mean concentrations of plasma and red blood cell (RBC) folate and plasma copper of the pregnant women were 38 (+/- 1, SD), 1,501 (+/- 374) nmol/L, and 32.7 (+/- 4.8) mumol/L, respectively, all of which were higher than those of healthy non-pregnant controls (p < 0.001). Mean concentrations of plasma vitamin B-12, zinc and iron levels and RBC zinc were 320 (+/- 130) pmol/L, 12.2 (+/- 2.3), 21.7 (+/- 6.1) and 177 (+/- 30) mumol/L and these were similar to those of non-pregnant controls. Amniotic fluid folate, zinc, copper and iron concentrations were 21 (+/- 13) nmol/L, 1.4 (+/- 0.6), 1.7 (+/- 0.6) and 6.8 (+/- 2.1) mumol/L, respectively, which were significantly lower than plasma levels (p < 0.001). However, this relationship was reversed for vitamin B-12 (650 +/- 420 pmol/L). Significant correlations were found between amniotic fluid and maternal plasma and RBC for folate, and between amniotic fluid and maternal plasma for vitamin B-12 (p < 0.001). No such correlations were observed for zinc, copper and iron. There was no correlation between amniotic fluid and/or blood nutrient concentrations and pregnancy outcome including birth weight of infants.

Immunological profile in a chromosome 18 deletion syndrome with IgA deficiency.

Autosomal deletion syndromes are of great interest since measurable loss of genetic material could lead to the mapping of the human autosomes. Short arm deletions and long arm deletions of chromosome 18 have been described in association with phenotypic changes (Grouchy et al., 1963, 1964) and reviewed recently by Wolf et al. (1967) and Reinwein, Ritter, and Wolf (1967). Since a ring chromosome presumably has double deficiencies resulting from the loss of the distal part of both arms, it was considered significant that a 15year-old female with a ring-18 chromosome was deficient in the immunoglobulin IgA in serum and saliva (Finley et al., 1968). In this report, we present detailed analysis of this patient and discuss some of the genetic implications of the association of chromosome 18 deletions and IgA deficiency.