Lamin B-receptor mutations in Pelger-Huët anomaly.

Pelger-Huët anomaly is an inherited abnormality of neutrophils, characterized by reduced nuclear segmentation and an apparently looser chromatin structure. Following linkage studies in two families, the lamin B-receptor (LBR) was sequenced and mutations found: CCG-->CTG causing proline-->leucine in codon 119 of exon 3, and IVS11-9 A-->G, disrupting the splice acceptor site. The LBR gene (LBR) was also sequenced from a single English man with Pelger-Huët anomaly and a heterozygous C-->G mutation was found in codon 569 of exon 14, predicted to cause a proline-->arginine. Our results confirm recently published findings that LBR mutations cause Pelger-Huët.

Cytogenetic and functional studies of leukocytes with Pelger-Huët anomaly.

A cytogenetic study was undertaken in 15 cases of Pelger-Huët (P-H) anomaly in 3 families. An enlarged short arm of chromosome 22 (22p+) was found in 14 cases, but in these families 4 cases without P-H anomaly did not show 22p+ in the karyotype. In P-H anomaly, delayed skin hypersensitivity reactions, levels of serum IgG, IgM and IgA, lymphocyte subpopulations, and natural killer and antibody-dependent, cell-mediated cytotoxicity activities were within normal range. The level of serum IgE, mitogen responses in peripheral blood lymphocyte and plaque-forming cell counts were also within normal range with the exception of a case with atopic eczema. Enzymatic activities, nitroblue tetrazolium reduction and phagocytic capacities of neutrophils appeared normal. Abnormalities of neutrophils in cases of P-H anomaly, as compared with normal subjects, were also negative in examinations for chemotaxis and spontaneous migration under agarose and in a membrane filter.

Studies of the Pelger-Huët anomaly in foxhounds.

An inbred family of foxhounds with four members expressing the Pelger-Huët (P-H) anomaly is described. The disease-free status of all P-H affected dogs suggests a benign disorder, although review of breeding records indicated a lower percentage of pups weaned (63%) by P-H females compared with the percentage of pups weaned (81%) by outcrossed females throughout the foxhound colony. Light-microscopic examination of blood films from affected dogs revealed 50--67% neutrophils with round, oval, or bean-shaped nuclei and rarely (0.5%) segmented nuclei. Neutrophils examined by electron microscopy showed the nuclei to have a fine nuclear cleft and condensed chromatin and the cytoplasm to have mature heterochromatic granulation. Local P-H neutrophil mobilization through a standard skin abrasion into a chamber containing autologous serum was impaired at all time periods evaluated (1, 4, 8, and 24 hours) compared with the neutrophil mobilization by normal dogs. Antibody response to sheep erythrocyte immunization was also impaired. In vitro reactivity of normal and P-H lymphocytes stimulated by pokeweed mitogen was depressed when lymphocytes were cultured in plasma from a P-H dog but not when cultured in plasma from a normal dog. Vigorous blastogenic responses to phytohemagglutinin by normal and P-H lymphocytes cultured in P-H or normal plasma suggest the presence of a factor(s) in the P-H plasma which interferes with B-lymphocyte reactivity.

Impaired neutrophil chemotaxis in Pelger-Huët anomaly.

A family has previously been described in which four members with Pelger-Huët (P-H) anomaly suffered from recurrent attacks of abdominal pain and fever, while one member, whose polymorphonuclear leucocytes (PMNs) were also hyposegmented, was asymptomatic. We studied chemotaxis, chemokinesis and spontaneous locomotion of PMNs in the three surviving symptomatic sisters, in their asymptomatic brother and in two asymptomatic members of another family with P-H anomaly. The spontaneous migration of the PMNs of the three sisters was significantly slower both under agarose and in a membrane filter than that of the PMNs of the asymptomatic patients with P-H anomaly. Chemotactic and chemokinetic locomotion of the PMNs of the symptomatic sisters was also slow. Our results suggests that the impaired chemotaxis was due to a defect in the intrinsic locomotor capacity of PMNs rather than in their deformability or their responsiveness to the chemotactic stimulus.

[Pelger-Huet anomaly]. / Pelger-Huetova anomalija.

A homozygot carrier of a congenital nuclear anomaly of blood cells/Pelger-Huet's anomaly: abnormal segmentation of granulocytic leukocytes) is described. The morphologic analysis of blood samples in 4 family members showed similar Pelger-Huet's anomalies. The phagocytic activity, the "killing test" and the inhibition test of leucocyte migration of the patients neutrophils were in normal ranges.