Microcephalic osteodysplastic primordial dwarfism type I with biallelic mutations in the RNU4ATAC gene.

Microcephalic osteodysplastic primordial dwarfism type I (MOPD I) is a rare autosomal recessive developmental disorder characterized by extreme intrauterine growth retardation, severe microcephaly, central nervous system abnormalities, dysmorphic facial features, skin abnormalities, skeletal changes, limb deformations, and early death. Recently, mutations in the RNU4ATAC gene, which encodes U4atac, a small nuclear RNA that is a crucial component of the minor spliceosome, were found to cause MOPD I. MOPD I is the first disease known to be associated with a defect in small nuclear RNAs. We describe here the clinical and molecular data for 17 cases of MOPD I, including 15 previously unreported cases, all carrying biallelic mutations in the RNU4ATAC gene.

Referral for cancer genetics consultation: a review and compilation of risk assessment criteria.

BACKGROUND: There have been many papers on the diagnostic criteria for specific hereditary cancer susceptibility syndromes and the likelihood that an individual has a germline mutation in one of the various cancer susceptibility genes. To assist health care professionals in deciding when a cancer genetics consultation is appropriate, available reports were critically reviewed in order to develop a single set of risk assessment criteria. METHODS: The criteria were based on a comprehensive review of publications describing diagnostic criteria for hereditary cancer syndromes and risk to first degree relatives of cancer patients. Priority was given to diagnostic criteria from consensus statements (for example, those from the National Comprehensive Cancer Network). Expert opinion from study personnel was then used to adopt a single set of criteria from other publications whenever guidelines differed. RESULTS: Based on family history, a set of criteria was developed to identify patients at risk for a hereditary cancer susceptibility syndrome, patients with moderate risk who might benefit from increased cancer surveillance, and patients who are at average risk. The criteria were applied to 4360 individuals who provided their cancer family history between July 1999 and April 2002, using a touch screen computer system in the lobby of a comprehensive cancer centre. They categorised an acceptable number of users into each risk level: 14.9% high risk, 13.7% moderate risk, and 59.6% average risk; 11.8% provided insufficient information for risk assessment. CONCLUSIONS: These criteria should improve ease of referral and promote consistency across centres when evaluating patients for referral to cancer genetics specialists.

Moped injuries in children.

Moped injuries are an important cause of traffic-related injuries in children. An attempt was made to define the epidemiology as well as the nature and severity of injuries sustained in 88 moped-related accidents. Bicycle injuries among children (579) were used as a control. The patients with moped injuries were younger than expected (mean 12.8 years with a minimum legal driving age of 14 years in the study area). Among 26 hospital admissions due to moped accidents, there were 11 admissions to the intensive care unit, demonstrating the severe nature of the injuries. Fifty percent of the patients had orthopaedic injuries and 46% had neurologic injuries. These injuries resulted in an average length of hospitalization of 8.5 days (intensive care unit admissions lasted an average of 14.6 days). Recommendations are made to aid pediatricians in the counseling of patients and parents.

Infantile spasms in two children with Williams syndrome.

We describe two children with Williams syndrome and infantile spasms. The diagnosis of Williams syndrome was confirmed by documentation of a deletion of the elastin gene/Williams syndrome region at 7q11.23. The diagnosis of infantile spasms was confirmed through the presence of interictal hypsarrhythmia. This represents one of the first reports of infantile spasms in the Williams syndrome.

Atypical Menkes steely hair disease.

Menkes steely hair disease (MSHD) is a rare disorder which typically results in severe mental retardation and death in early childhood. A 21-month-old boy with an atypical milder form was presented by Procopis et al. [1981]. A second child with the atypical form is presented here who has survived to age 9 years and is doing well clinically.

Fine mapping of glycerol kinase deficiency and congenital adrenal hypoplasia within Xp21 on the short arm of the human X chromosome.

We have studied patients with Duchenne muscular dystrophy (DMD), DMD together with glycerol kinase (GK) deficiency, or DMD together with both GK deficiency and congenital adrenal hypoplasia (AHC). Analysis of deletions in these patients allows the mapping of these mutations in Xp21. The following order is proposed: Xpter - L1 - AHC - GK - DMD - Xcen. One of the boys with DMD, GK, and AHC is shown by pulsed-field-gel electrophoresis to have a deletion which has a proximal endpoint at least 500 kb distal from the pERT87 (DXS164) locus.

Clinical characteristics associated with dup17(q24q25.1) in a mosaic mother and two non-mosaic daughters.

We present cytogenetic and clinical findings in a familial case of dup(17)(q24q25.1). The duplication was transmitted from the mosaic mother to two non-mosaic daughters. This is the first report involving duplication of 17q24q25.1. Manifestations in our three patients were similar to those in previously reported cases with 17q partial duplications, but also included brachydactyly and craniosynostosis. These findings represent additional clinical characteristics of distal 17q duplication and may indicate the presence of gene(s) involved in skeletal development in this region, duplication of which may result in a phenotype resembling Ullrich-Turner syndrome.

Influence of pH and temperature on the luminol-dependent chemiluminescence of human polymorphonuclear leucocytes.

Human polymorphonuclear leucocytes were stimulated with the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine and the luminol-dependent chemiluminescence produced was measured as a function of pH in the interval 6.85-7.70 and as a function of temperature in the interval 21-37 degrees C. The time response of the chemiluminescence signal after addition of the peptide consisted of two peaks at 21 degrees C. The separation in time between the maxima of the two peaks and the width of the second peak decreased with increasing temperature. The two peaks coalesced at 37 degrees C. The intensity of the initial peak showed a strong pH dependence, whereas the second peak was rather insensitive to pH changes. The results point to the importance of a rigorous control of pH and temperature if quantitative luminol-dependent chemiluminescence measurements are to be made. The results of this work also support the view that the initial peak originates from reactions taking place at the outside of the cell and that the second peak is caused by intracellular reactions.

Gastrointestinal hemorrhage associated with gastric polyps in Menkes disease.

We describe two infants with Menkes disease who had serious gastrointestinal bleeding from solitary gastric polyps. Hemorrhage in one patient was acute and proved fatal. Histopathologic examinations showed submucosal vascular ectasia with mucosal hyperplasia, edema, and ulceration. Gastric polyps may represent an underappreciated clinical abnormality in Menkes disease.