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40 patients with bone disease due to chronic renal failure have been treated with 1 alpha-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 for a total of 750 patient-months. Both compounds were very effective in relieving bone pain and muscle weakness, and in reversing the radiographic and biochemical indices of disturbed skeletal metabolism. Their effects as judged from bone biopsies were, however, less complete, and histological improvement occurred only in a few patients. Patients with the combination of osteitis fibrosa and osteomalacia responded better than patients with either abnormality alone. Factors of importance in adversely influencing the outcome of treatment included a high pre-treatment level of calcium or immunoreactive parathyroid hormone, and a failure to augment secretion of calcitonin during treatment. It is concluded that a major therapeutic advantage of 1 alpha-OHD3 and 1,25(OH)2D3 over previously available forms of vitamin D is their rapid onset and reversal of action. These drugs do not invariably reverse bone disease and may give rise to unwanted effects. They should therefore only be used with adequate clinical, biochemical and radiographic supervision. They should not be used indiscriminately in all renal patients.

Background: Human autosomal recessive primary microcephaly (MCPH) is a heterogeneous disorder with at least six genetic loci (MCPH1–6), with MCPH5, caused by ASPM mutation, being the most common. Despite the high prevalence of epilepsy in microcephaly patients, microcephaly with frequent seizures has been excluded from the ascertainment of MCPH. Here, we report a pedigree with multiple affected individuals with microcephaly and seizures. Objective: To identify the gene responsible for microcephaly and seizures in this pedigree. Methods: Clinical assessments of three patients and brain MRIs of two patients were obtained. Genome-wide linkage screen with 10 k SNP microarray, fine mapping with microsatellite markers, and mutational analysis of the genomic DNA were performed on the pedigree. Results: We found that the family was linked to the MCPH5 locus on chromosome 1q31.2–q32.1. We screened ASPM and identified a previously unreported nonsense mutation that introduced a premature stop codon in exon 18 of the ASPM gene. Conclusions: We thus expand the clinical spectrum of ASPM mutations by showing that they can occur in patients with seizures and that the history of seizures alone should not necessarily preclude the diagnosis of primary microcephaly.

Background: Syndromes of bilateral symmetric polymicrogyria include an autosomal recessive form of bilateral frontoparietal polymicrogyria (BFPP), in which the malformation is most severe rostrally. The authors describe a new syndrome they have termed “bilateral generalized polymicrogyria” (BGP), in which the malformation occurs in a generalized distribution but is often most severe in the perisylvian regions. Methods: Patients with bilateral polymicrogyria were identified from multiple medical centers worldwide. The diagnosis of BGP was based on findings from conventional spin echo MRI and, in one case, postmortem neuropathologic findings. Genetic analysis was performed for those patients from consanguineous pedigrees and those with multiple affected siblings to rule out linkage to the BFPP locus on chromosome 16q. Results: Twelve patients were identified with BGP. Clinical features included cognitive and motor delay as well as seizures. Some specific features characteristic of other known bilateral polymicrogyria syndromes, such as pseudobulbar palsy and dysconjugate gaze, were not commonly seen in these patients. Radiologically, polymicrogyria appeared widespread but was often most severe in the perisylvian regions. Pathologic examination in one case revealed a diffusely thin and excessively folded cerebral cortex lacking normal six-layered architecture. Seven patients subjected to genetic analysis did not demonstrate linkage to the BFPP locus. Conclusions: BGP is a distinct syndrome of cortical malformation. Several features allow BGP to be distinguished from other disorders on the growing list of bilateral symmetric polymicrogyria syndromes.

We have studied 23 children from 13 families with a clinical diagnosis of Aicardi-Goutières syndrome. Affected individuals had developed an early-onset progressive encephalopathy that was characterized by a normal head circumference at birth, basal ganglia calcification, negative viral studies, and abnormalities of cerebrospinal fluid comprising either raised white cell counts and/or raised levels of interferon-alpha. By means of genomewide linkage analysis, a maximum-heterogeneity LOD score of 5.28 was reached at marker D3S3563, with alpha=.48, where alpha is the proportion of families showing linkage. Our data suggest the existence of locus heterogeneity in Aicardi-Goutières syndrome and highlight potential difficulties in the differentiation of this condition from pseudo-TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus types 1 and 2) syndrome.

Mortality from cancer among 178 parents and 236 grandparents of 95 British patients with ataxia-telangiectasia was examined. For neither parents nor grandparents was mortality from all causes or from cancer appreciably elevated over that of the national population. Among mothers, three deaths from breast cancer gave rise to a standardized mortality ratio of 3.37 (95% confidence interval (CI): 0.69–9.84). In contrast, there was no excess of breast cancer in grandmothers, the standardized mortality ratio being 0.89 (95% CI: 0.18–2.59), based on three deaths. This is the largest study of families of ataxia-telangiectasia patients conducted in Britain but, nonetheless, the study is small and CIs are wide. However, taken together with data from other countries, an increased risk of breast cancer among female heterozygotes is still apparent, though lower than previously thought. © 1999 Cancer Research Campaign

A whole X chromosome study of families in which Rett syndrome had been diagnosed in more than one member indicated that the region between Xq27 and Xqter was the most likely region to harbour a gene which may be involved in the aetiology of the disease. Further, more detailed studies of Xq28 detected weak linkage and a higher than expected sharing of maternally inherited alleles. It is suggested that there may be more than one gene involved in the aetiology of this syndrome, particularly as the very rare families in which more than one girl is affected often show variable clinical symptoms.

DNA mapping studies in two families provide further information on the Angelman syndrome critical region, which has recently been defined by the gene UBE3A. The first family has probable familial Angelman syndrome with a maternally imprinted inheritance pattern. A 5 year old girl with this disorder has a 14 year old brother and an 11 year old male cousin who have less typical clinical features. DNA microsatellite analysis has shown that the three share a common segment of the same grandpaternal chromosome 15q11-q13 that overlaps with UBE3A. The child with typical Angelman syndrome has an additional maternal recombination 5' to UBE3A. The second family is a mother and son both of whom have mental retardation but no other features of Angelman syndrome despite an extensive DNA deletion on the telomeric side of UBE3A. Together, the two families identify a region between loci D15S210 and D15S986 which forms part of the Angelman syndrome critical region. A new microsatellite (D15S1234) is described which can be used in place of the LS6-1 marker at locus D15S113.

The clinical features, investigation, treatment and outcome of two adults with fibrogenesis imperfecta ossium are described. In this rare acquired disorder of bone, normal lamellar collagen is replaced by structurally unsound collagen-deficient tissue, which leads to extreme bone fragility and ununited fractures. Transmission microscopy and SEM showed striking ultrastructural changes in bone structure and mineralisation. Both patients had monoclonal IgG paraproteins in the plasma and one excreted monoclonal lambda light chains in the urine. No abnormal plasma cells were found in the bone marrow and there was no evidence of amyloid deposition in the tissues. In both patients initial treatment with 1 alpha-hydroxycholecalciferol appeared to be ineffective, but in one, repeated courses of melphalan and corticosteroids over three years together with 1 alpha-hydroxycholecalciferol produced striking clinical and histological improvement. The findings in these and other patients strongly suggest that paraproteinaemia is an integral feature of fibrogenesis imperfecta ossium, and this needs further investigation.

We report an infant with pre- and postnatal microcephaly and growth retardation, a distinctive face, and developmental delay. The initial diagnosis was of Seckel syndrome. He became pancytopenic at 16 months and died soon after. His bone marrow was of normal cellularity but had a small lymphocyte infiltration. Increased spontaneous chromosome breakage was seen in blood and fibroblasts. Mitomycin C induced chromosome damage was increased and comparable to that seen in Fanconi anaemia. Reports of similar patients are reviewed. This entity of severe intrauterine growth retardation and increased mitomycin C sensitivity is hypothesised to be a distinct chromosome breakage syndrome.

We report a family in which two sibs have both achondroplasia and pseudoachondroplastic dysplasia. The mother has achondroplasia and the father has pseudoachondroplastic dysplasia, which he had inherited from his father. Both children appeared typical of achondroplasia at birth. By 1 1/2 years they had developed a fixed lumbar kyphosis with gibbus and had additional x ray changes unusual for just achondroplasia and suggestive of pseudoachondroplastic dysplasia. Subsequently both children have shown characteristic features of both conditions and have grown less well than expected for achondroplasia. Radiographs show the striking synergistic effects of the two conditions. MRI in both sibs confirmed brain stem compression at the foramen magnum. This may be an important complication and should be actively sought in any double heterozygote.

Editor—Rett syndrome is a severe, progressive, neurodevelopmental disorder which almost exclusively affects females. At first the affected girls appear to develop normally but after a year to 18 months they begin to deteriorate. Not only do they fail to progress but they lose skills already learnt until finally they have severe developmental delay with dementia and autistic behaviour, an apraxic gait, breathing dysfunction, and stereotyped hand movements, such as excessive hand wringing. Lost skills are not regained.1 The disease, which affects ∼1 in 10 000 girls, accounts for about 10% of profound handicap in females. More than 95% of cases are sporadic leading to the assumption that the syndrome must be the result of an X linked dominant gene with male lethality. Thomas2 has also suggested that the lack of males with the syndrome could be accounted for by the increased rate of de novo germline mutations in males. This would imply that affected females arise as a consequence of de novo mutations in their fathers. Marked skewing of X inactivation has not been detected in sporadic cases of the syndrome either in affected girls or in their mothers,3 but in one familial case the mother of three affected girls was found to have >95% skewing of inactivation in favour of the normal chromosome remaining preferentially active.4 The few available familial cases allowed the gene to be mapped to Xq285 6 and in 1999 Amir et al 7 reported that mutations in the MECP2 gene, located in Xq28, were associated with Rett syndrome in 5/21 of de novo cases. Amir et al 7 and Wan et al 8 reported …

Ciliopathies are an expanding group of rare conditions characterized by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS), Senior-Loken syndrome and isolated Leber congenital amaurosis (LCA). Although these conditions are recessively inherited, in a subset of patients only one CEP290 mutation could be detected. To assess whether genomic rearrangements involving the CEP290 gene could represent a possible mutational mechanism in these cases, exon dosage analysis on genomic DNA was performed in two groups of CEP290 heterozygous patients, including five JSRD/ MKS cases and four LCA, respectively. In one JSRD patient, we identified a large heterozygous deletion encompassing CEP290 C -terminus that resulted in marked reduction of mRNA expression. No copy number alterations were identified in the remaining probands. The present work expands the CEP290 genotypic spectrum to include multiexon deletions. Although this mechanism does not appear to be frequent, screening for genomic rearrangements should be considered in patients in whom a single CEP290 mutated allele was identified.

Background: The VACTERL with hydrocephalus (VACTERL-H) phenotype is recognised to be a severe manifestation of autosomal recessive Fanconi anaemia. Several families have been described in which the VACTERL-H phenotype segregates as an X linked syndrome. The mutations which cause X linked VACTERL-H syndrome are not known. Objective: To determine if mutations in FANCB , which are known to cause Fanconi anaemia complementation group B, are a cause of X linked VACTERL-H syndrome. Methods: A three generation pedigree with X linked VACTERL-H syndrome was investigated. X inactivation was tested in carrier females, and fibroblasts from an affected male fetus were analysed for increased sensitivity to diepoxybutane. FANCB coding exons and flanking splice sites were screened for mutations by direct sequencing of polymerase chain reaction (PCR) fragments amplified from genomic DNA. cDNA from affected fetal fibroblasts was analysed by PCR and direct sequencing using specific exonic primers. Results: A FANCB mutation which results in a premature stop codon by causing skipping of exon 7 was identified. Chromosomes from the affected fetus showed increased sensitivity to diepoxybutane, and carrier women were found to have 100% skewed X inactivation in blood. Conclusions: Mutations in FANCB are a cause of X linked VACTERL-H syndrome. The data presented are of relevance to the genetic counselling of families with isolated male cases of VACTERL-H and Fanconi anaemia.

We report three related and one unrelated child with an apparently novel neurodevelopmental disorder. The clinical course was very similar in all the four patients: congenital microcephaly with severe failure of post-natal brain growth, neonatal onset of intractable seizures associated with lack of developmental progression and death within the first 3 years of life. The appearance on cerebral neuroimaging was almost identical, with simplified gyration associated with a non-thickened cortex, severe hypoplasia of the corpus callosum, a small flattened brain stem, and specific cystic lesions in the white matter around the temporal and occipital horns. To our knowledge these patients represent a previously unreported, autosomal recessive syndrome. Homozygosity mapping in the consanguineous family has identified a candidate region on the chromosome 2p16.

We report on three children from two families with Aicardi-Goutières syndrome. All three had congenital glaucoma. Additionally, neuroimaging demonstrated significant brain stem atrophy in the affected sib-pair. These features have not been previously described in Aicardi-Goutières syndrome and expand the phenotypic spectrum.

We present two siblings (male and female) with very similar characteristics comprising dysmorphic features, severe developmental delay, progressive microcephaly, tonic seizures, and hypothyroidism. The male also had micropenis and cryptorchidism. Both children developed pericardial effusions which caused the death of the female at age 16 months. The male's cardiac function was stable at last follow-up at the age of 15 months. Cerebral imaging showed widespread intracranial calcifications, delay in myelination, hypoplasia of the corpus callosum, and cerebral atrophy. CSF examination showed normal CSF white-cell count and was negative for interferon, although a cytotoxic antibody was thought to be present. Other causes of a neurodegenerative condition and congenital infection were excluded. The combination of these features has not been described before. We believe that these patients represent a new syndrome which has some of the features of Aicardi-Goutières syndrome but is distinct from it.

We present two siblings (male and female) with very similar characteristics comprising dysmorphic features, severe developmental delay, progressive microcephaly, tonic seizures, and hypothyroidism. The male also had micropenis and cryptorchidism. Both children developed pericardial effusions which caused the death of the female at age 16 months. The male's cardiac function was stable at last follow-up at the age of 15 months. Cerebral imaging showed widespread intracranial calcifications, delay in myelination, hypoplasia of the corpus callosum, and cerebral atrophy. CSF examination showed normal CSF white-cell count and was negative for interferon, although a cytotoxic antibody was thought to be present. Other causes of a neurodegenerative condition and congenital infection were excluded. The combination of these features has not been described before. We believe that these patients represent a new syndrome which has some of the features of Aicardi-Goutieres syndrome but is distinct from it.

To date, Micro syndrome has been reported in only three children from one family. We describe an additional 14 children from 11 families.Retrospective case series.Fourteen children from 11 families attending one of five British hospitals.The following features were documented: pre- and postoperative eye findings, electrophysiologic analysis, systemic abnormalities, development, neuroimaging, genealogy, geographic origin of family.We expand and modify the description of ocular and electrophysiologic findings in Micro syndrome. The eye findings of microphakia, microphthalmos, characteristic lens opacity, and atonic pupils were the presenting feature in all infants and were the most reliable diagnostic signs in the immediate postnatal period. Cortical visual impairment, microcephaly, and developmental delay were not always detectable initially; they developed in all children by 6 months of age. Microgenitalia were a useful diagnostic clue in affected males only. Therefore, eye features were more consistently useful in determining diagnosis than dysmorphology or brain imaging. The families of all the children originate from the Muslim population of Northern Pakistan. Inheritance is likely to be autosomal recessive.Micro syndrome usually presents to the ophthalmologist, who may be able to make the diagnosis on the basis of characteristic eye findings combined with ethnic origin. Initially, the nature and severity of nonophthalmic features are not apparent. Early diagnosis of the underlying condition is important to guide management of the cataracts, glaucoma, and developmental delay. It is helpful for the family and medical staff to be aware of the low level of vision that develops despite optimal ophthalmic intervention. Genetic counseling extending into the wider family is particularly important in view of the high rate of consanguinity.

We describe a brother and sister who both had holoprosencephaly, polydactyly, cardiac lesions and a normal karyotype. The parents were first cousins and a diagnosis of pseudotrisomy 13 syndrome is suggested. This report provides further support that the inheritance of pseudotrisomy 13 syndrome is autosomal recessive.

Calcium pyrophosphate dihydrate (CPPD) crystal deposits were found in an extraarticular chondroma of the soft parts overlying the distal phalanx of the right middle finger. The lesion appeared to arise from the flexor tenosynovium. The pathogenesis of soft tissue chondroma and the relation of cartilage metaplasia to the process of CPPD crystal deposition were investigated.

The clinical features, investigation, treatment and outcome of two adults with fibrogenesis imperfecta ossium are described. In this rare acquired disorder of bone, normal lamellar collagen is replaced by structurally unsound collagen-deficient tissue, which leads to extreme bone fragility and ununited fractures. Transmission microscopy and SEM showed striking ultrastructural changes in bone structure and mineralisation. Both patients had monoclonal IgG paraproteins in the plasma and one excreted monoclonal lambda light chains in the urine. No abnormal plasma cells were found in the bone marrow and there was no evidence of amyloid deposition in the tissues. In both patients initial treatment with 1 alpha-hydroxycholecalciferol appeared to be ineffective, but in one, repeated courses of melphalan and corticosteroids over three years together with 1 alpha-hydroxycholecalciferol produced striking clinical and histological improvement. The findings in these and other patients strongly suggest that paraproteinaemia is an integral feature of fibrogenesis imperfecta ossium, and this needs further investigation.

The presence of chondrocalcinosis in a knee which otherwise fulfils the criteria for unicompartmental knee arthroplasty has been considered a contraindication to this procedure. This paper compares the results of two groups of patients undergoing unicompartmental knee arthroplasty; there were 78 knees with degenerative arthritis, and 20 knees with degenerative arthritis and chondrocalcinosis, as proven histologically. The survival rates were not significantly different as determined by the log rank test. There was no significant difference between the groups using pain scores as an outcome measure, nor radiologically. We believe that chrondocalcinosis is not a contraindication to unicompartmental knee arthroplasty.

We described a male infant with a spectrum of anomalies compatible with the diagnosis of 'disorganization-like syndrome'. The infant had a partial foot arising from the right buttock, an absent right kidney, and a shortened right leg with severe non-positional talipes equinovarus. The infant's karyotype was 47,XXY. The right common iliac artery was one half of the expected diameter. The limb reduction defect seen in this case of disorganization (Ds) may have had a vascular aetiology.

We report six persons mosaic for a chromosome anomaly. All were mentally retarded and dysmorphic. Unilateral or asymmetrical features were found in all cases, in one an unusual transverse terminal limb anomaly, and in the others various degrees of hemiatrophy of the left side of the body. Five of the subjects had skin pigmentary anomalies which were distributed in the lines of Blaschko. The abnormal cell lines found were ring chromosome 22, trisomy 22, a large acrocentric marker, a deletion of 18q, a deletion of 8q, and triploidy. In four cases the clinical diagnosis was only confirmed by skin biopsy. In one case low level mosaicism in blood was fortuitously detected because of cytogenetic fragile X screening and confirmed in a skin biopsy. The sixth case was of dynamic mosaicism of a non-mosaic deletion 18q with a chromosome 18 derived marker present in a proportion of cells. Chromosome mosaicisn may cause subtle and asymmetrical clinical features and can require repeated cytogenetic investigations. The diagnosis should be actively sought as it enables accurate genetic counselling to be given.

Webb T, Watkiss E, Woods CG. Neither uniparental disomy nor skewed X-inactivation explains Rett syndrome. Clin Genet 1993: 44: 236–240. © Munksgaard, 1993 The locus DXS255 was studied using the probe M27β in ten probands with Rett syndrome and in eight of their families. No evidence of uniparental disomy of the X chromosome was detected, as all informative probands had inherited an allele from each of their parents. Differential methylation of a CCGG site within the DXS255 locus as shown by digestion with Mspl/Hpall, revealed moderate skewing of X-inactivation favouring the maternal allele in two of the probands. Random X-inactivation was present in all mothers tested and in two unaffected sisters. Three of four unaffected siblings had inherited the same maternal allele at DXS255.

Beta 2-microglobulin amyloid deposition is associated with a destructive arthropathy in the hip of chronic hemodialysis patients. Twenty-five hips from 18 patients were assessed for the presence and immunohistochemical type of amyloid. The hemodialysis group was compared with an age- and disease-matched control group that had no evidence of renal failure. Beta 2-microglobulin amyloid deposits were present in all patients who had been on hemodialysis for 18 months or more. Beta 2-microglobulin amyloid deposits were not found in patients who had been on hemodialysis for less than 18 months. Amyloid deposits were seen first in the articular cartilage and later involved the synovial membrane, joint capsule, and subchondral bone as well. The presence and amount of amyloid deposition correlated to the duration of hemodialysis. Severely affected hip roentgenographically had a concentric loss of joint space, periarticular erosions, and cystic lesions in the femoral head and acetabulum. These pathologic and roentgenographic changes suggest that amyloid deposition leads directly to the erosive hip arthropathy occurring in hemodialysis patients.

We have studied an inbred family in which two cousins presented with the same clinical features of ataxia telangiectasia (AT). Both patients are still ambulatory at ages 25 and 20. Cellular features of both patients are typical of AT and include increased radiosensitivity and an increased level of spontaneously occurring chromosome aberrations in peripheral blood lymphocytes. Linkage studies and haplotype analysis show no clear evidence that the gene for AT in this family is on chromosome 11q22-23. As previously reported AT families from complementation groups AB, C, and D have all shown linkage to this region of 11q22-23. Our study is of importance in suggesting additional locus heterogeneity.

Ataxia-telangiectasia (A-T) is a progressive neurological disorder with a birth frequency of about 1 in 300,000 (Swift et al., 1986; Woods et al., 1990). The major neurological features include progressive cerebellar ataxia presenting in infancy, oculomotor dyspraxia, and dysarthria (Sedgwick and Boder, 1991). About 10% of all A-T homozygotes develop a malignancy in childhood or early adulthood. A minority of tumours are epithelial cell cancers but with an unusually high predisposition to stomach carcinoma and smaller excesses of liver, uterine and ovarian tumours (Spector et al., 1982). The vast majority of tumours are however lymphoid in origin. All the leukaemias reported by Spector et al. (1982) were lymphoid with no myeloid tumours. A 70-fold and 250-fold excess of leukaemias and lymphomas respectively was reported by Morell et al. (1976).

Cytogenetic studies have been carried out on a series of nine girls with Rett syndrome, six of their mothers and nine normal female controls. No abnormality of the X-chromosome has been observed in any subject. X-inactivation studies using various methods of detecting the timing of individual band replication were performed. The overall pattern seen was essentially the same in all subjects, but in the patients with Rett syndrome there may be an alteration in the timing of the X-inactivation process in the region Xp11.3 or 4-->Xp21.

A male infant, whose parents were first cousins, was born with tense chylous ascites, mild generalized oedema and facial dysmorphism. The baby initially seemed well but subsequently probably aspirated, developed septicaemia and finally died at 26 days from a bleeding diathesis, possibly secondary to liver dysfunction. No cause for the chylous ascites was found at post mortem. This case is presumed to represent an example of recessively determined chylous ascites. The mouse mutant Chy may be an homologous condition.

This paper describes three children of a Pakistani first cousin marriage with a distinctive, non-progressive disorder characterised by variable phalangeal anomalies, microcephaly, pre- and postnatal growth retardation, poor vision, dystonic movements, a characteristic face, and severe mental retardation. This combination of features seems to be distinct and to represent a new autosomal recessive syndrome.

Seventy individuals with ataxia telangiectasia were studied: 29 females and 41 males with an age range of 2 to 42 years. The majority (43/68) presented by 3 years of age with truncal ataxia. All had progressive, handicapping neurological symptoms exhibiting ataxia (70/70), ocular motor apraxia (70/70), an impassive face (70/70), dysarthria (70/70), chorea (68/70), dystonia (55/70) and peripheral neuropathy (50/70). Clinical immune deficiency was present in 43 of 70 patients. Ocular telangiectasia were seen in all but one case and excessive thinness in 54 of 70. The mean age of loss of walking was 10 years and of writing 8 years. All 60 tested showed increased sensitivity to ionizing irradiation, 43 of 48 had an elevated alpha-fetoprotein level and 14 of 21 had an immunoglobulin deficiency. Although there was a marked variation in disease findings sibs were always similar. The heterogeneity seen seems at odds with the unilocus linkage of ataxia telangiectasia to 11q23.

A case is presented of a 37-year-old man with an extrinsic lesion originating in the soft tissue adjacent to the 3rd metatarsal and smoothly eroding the adjacent bone. The operatively confirmed diagnosis of fibroma of tendon sheath was surprising, giant cell tumour of tendon sheath eroding bone being considerably more common; these two lesions are normally impossible to distinguish radiologically.

In decalcified (5% nitric acid) and undecalcified (glycol-methacrylate or resin embedded) routinely processed bone specimens osteoclasts against resorbing surfaces were identified with monoclonal antibodies directed against leucocyte common antigen (LCA) (PD7/26, 2B11), CD68 (KP1), and gpIIIa (Y2/51) but not against HLA-DR (CR3/43 and Ta11B5). Mononuclear cells on resorbing surfaces and occasional mononuclear cells against or near resting surfaces showed a similar pattern of reactivity. This study shows that immunohistochemistry is a sensitive and useful technique for identifying osteoclasts in routinely processed bone specimens. It also suggests a role for mononuclear cells (possibly pre-osteoclasts) in bone resorption.

Seventy-six patients underwent parathyroidectomy for renal hyperparathyroidism. There were 10 subtotal parathyroidectomies, 49 total parathyroidectomies with implantation of part of one gland as an autograft, nine total parathyroidectomies with no autograft, and eight patients in whom only three parathyroid glands were found. In 34 dialysis patients who underwent total parathyroidectomy with an autograft there was a high rate of recurrent hyperparathyroidism after 6 years in those remaining on dialysis. Fifty per cent had asymptomatic recurrent hyperparathyroidism and 30 per cent required partial autograft excision for symptomatic hyperparathyroidism. In contrast, recurrent hyperparathyroidism was rare in renal transplant recipients with good renal function. This favourable outcome did not depend upon whether parathyroid surgery was performed before or after transplantation, or on the type of parathyroidectomy. Total parathyroidectomy without an autograft was performed in nine dialysis patients without any short-term adverse effects, and with clinical and pathological improvement in bone disease. In summary, the results of surgery for renal hyperparathyroidism were excellent in patients who received a successful renal transplant. However, there was a high incidence of recurrent hyperparathyroidism in patients who remained on long-term dialysis. Total parathyroidectomy without an autograft may be the treatment of choice in patients unlikely to receive a renal transplant.

Ataxia telangiectasia (A-T) is an autosomal recessive disorder characterised by progressive neurological degeneration, oculocutaneous telangiectasia, immunodeficiency and a high incidence of lymphoid tumours. A prerequisite to gaining a complete understanding of the basic defect that results in these features is the localization of the gene(s) involved. We report here a linkage analysis using seven polymorphic markers, which map to 11q22-23, on a sample of 35 consecutively obtained families from the British Isles showing this disorder. In a pairwise analysis, the strongest support for linkage was a lod score of 4.01 at zero recombination from Thy-1. This result supports a previous report showing linkage of the A-T gene to 11q22-23. We have also obtained evidence in a multipoint analysis for a more centromeric A-T-linked locus in the region between YNB 3.12/CJ52.208 and 2-7-1D6. This observation is also supported by inspection of the haplotypes of selected recombinants.