Terminal deletion of chromosome 4p (4p16.3) shows a breakpoint between loci linked to Huntington disease

A 15-year-old boy with a terminal deletion of the short arm of chromosome 4 is described. The patient has a mild clinical phenotype that is incompatible with Wolf-Hirschhorn syndrome. Careful neurological examination including CT scan did not show any signs of Huntington disease. The chromosomal breakpoint was analyzed by means of polymorphic DNA probes localized close to the tentative Huntington (HD) locus. The breakage has occurred between D4S43 and D4S90 loci and thus deletes part of the chromosomal candidate regions for the HD locus. © 1992 Wiley-Liss, Inc.     

Synthetic env gp41 peptide as a sensitive and specific diagnostic reagent in different stages of human immunodeficiency virus type 1 infection

An enzyme immunoassay (EIA) for serum antibodies to human immunodeficiency virus type 1 (HIV-1), based on the synthetic pentadecapeptide SGKLICT-TAVPWNAS, a segment of the transmembrane glycoprotein (gp41) of the virus, was developed and tested for sensitivity and specificity. Sera of 152 individuals at various stages of HIV-1 infection, including two prospectively and six retrospectively studied patients exposed to HIV-1 but seronegative on initial testing in whole-virus EIA and immunoblotting, were screened with the gp41 peptide antibody EIA. The reference population consisted of 1,000 healthy HIV-1 antibody-negative blood donors. In addition, five individuals with antibodies to HIV-2 were studied. Antibodies to the synthetic peptide were detected in 100% of those with asymptomatic infection. Only one patient with LAS failed to react in the peptide EIA. Patients with HIV-2 infection did not react in this test. The peptide antibodies appeared rapidly after infection, were detectable at the time when seroconversion was observed by immunoblotting, and preceded reactivity in whole-virus EIA. Sera of seven patients with verified HIV-1 infection did not react with gp41 in immunoblotting, although antibodies were readily detectable in the gp41 peptide EIA.     

Natural history of oral papillomavirus infections in spouses: a prospective Finnish HPV Family Study.

BACKGROUND: The natural history of genital human papillomavirus infection is well known, but nearly nothing is known about the outcome of oral HPV-infection. OBJECTIVES AND STUDY DESIGN: To study natural history of oral HPV in spouses during the follow-up 331 women (mean 25.5+/-3.4 years) and 131 men (mean 28.8+/-5.0 years) were recruited from maternity unit. Scrapings from healthy oral mucosa of spouses at baseline, 2, 6, 12 and 24 months and genital samples were taken for HPV testing. HPV DNA was detected by nested PCR and confirmed by hybridization using a cocktail of 12 high-risk (HR) oligoprobes. RESULTS: The detection rate of HR HPVs varied from 15% to 27%. Baseline oral HPV status between the spouses was closely related (odds ratio 4.3; 95% confidence interval 1.6-12.0; P=0.006). Persistent oral infection in one spouse was a significant risk factor (odds ratio 10.0; 95% confidence interval 1.5-68.7; P=0.005) for oral HR HPV persistence in the other partner. Cumulative incidence of new HR HPV infections was identical in both spouses, while men seemed to clear their infection more rapidly. In univariate survival analysis, the partner's oral or genital HPV status, oral sex habits or age did not predict clearance or acquisition of oral HR HPV. CONCLUSION: Natural history of HPV infection in oral mucosa mimics that of genital HPV infection. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection 10-fold in the other spouse.     

Emergence of racial/ethnic and socioeconomic differences in objectively measured sleep–wake patterns in early infancy: results of the Rise & SHINE study

Study ObjectivesTo characterize objectively assessed sleep–wake patterns in infants at approximately 1 month and 6 months and examine the differences among infants with different racial/ethnic backgrounds and household socioeconomic status (SES).MethodsFull-term healthy singletons wore an ankle-placed actigraph at approximately 1 month and 6 months and parents completed sleep diaries. Associations of racial/ethnic and socioeconomic indices with sleep outcomes were examined using multivariable analyses. Covariates included sex, birth weight for gestational age z-score, age at assessment, maternal education, household income, bed-sharing, and breastfeeding.ResultsThe sample included 306 infants, of whom 51% were female, 42.5% non-Hispanic white, 32.7% Hispanic, 17.3% Asian, and 7.5% black. Between 1 month and 6 months, night sleep duration increased by 65.7 minutes (95% CI: 55.4, 76.0), night awakenings decreased by 2.2 episodes (2.0, 2.4), and daytime sleep duration decreased by 73.3 minutes (66.4, 80.2). Compared to change in night sleep duration over this development period for white infants (82.3 minutes [66.5, 98.0]), night sleep increased less for Hispanic (48.9 minutes [30.8, 66.9]) and black infants (31.6 minutes [−5.9, 69.1]). Night sleep duration also increased less for infants with lower maternal education and household income. Asian infants had more frequent night awakenings. Adjustment for maternal education and household income attenuated all observed day and night sleep duration differences other than in Asians, where persistently reduced nighttime sleep at 6 months was observed.ConclusionsRacial/ethnic differences in sleep emerge in early infancy. Night and 24-hour sleep durations increase less in Hispanic and black infants compared to white infants, with differences largely explained by SES.     

Dominant GDAP1 founder mutation is a common cause of axonal Charcot-Marie-Tooth disease in Finland

We describe a founder mutation in the gene encoding ganglioside-induced differentiation associated-protein 1 (GDAP1), leading to amino acid change p.H123R, as a common cause of autosomal dominant axonal Charcot-Marie-Tooth (CMT2) neuropathy in Finland. The mutation explains up to 14 % of CMT2 in Finland, where most patients with axonal neuropathy have remained without molecular diagnosis. Only three families out of 28 were found to carry putative disease mutations in the MFN2 gene encoding mitofusin 2. In addition, the MFN2 variant p.V705I was commonly found in our patients, but we provide evidence that this previously described mutation is a common polymorphism and not pathogenic. GDAP1-associated polyneuropathy caused predominantly a mild and slowly progressive phenotype. Besides distal leg muscle weakness, most patients showed mild proximal weakness, often with asymmetry and pes cavus. Our findings broaden the understanding of GDAP1 mutations in CMT2 phenotypes and provide support for the use of whole-exome sequencing in CMT gene diagnostics.     

Construct and predictive validity of a self-reported measure of preclinical mobility limitation

OBJECTIVES: To validate self-reported preclinical mobility limitation concept and self-report assessment method against muscle power and walking speed, and to study the predictive validity of preclinical mobility limitation with respect to future risk of manifest mobility limitation. DESIGN: Observational prospective cohort study and cross-sectional analysis. SETTING: Research laboratory and community. PARTICIPANTS: A total of 632 community-living (age range, 75-81 y) women and men took part in the baseline assessments and 302 persons in the semi-annual interviews on mobility limitation over 2 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Walking speed, muscle power, and self-reported preclinical and manifest mobility limitation. Preclinical mobility limitation was defined as self-reported tiredness or modification of task performance without task difficulty. At baseline, 4 subgroups were created according to self-reported preclinical mobility limitation in any of 3 mobility tasks (walking 2 km, walking 0.5 km, climbing up stairs): no limitation, preclinical limitation, and minor and major manifest limitation. RESULTS: At baseline, participants with preclinical mobility limitation showed intermediate levels of walking speed and muscle power, compared with those with no limitation or manifest mobility limitation. Participants reporting baseline preclinical mobility limitation had 3- to 6-fold higher age- and sex-adjusted risk of progressing to major manifest mobility limitation during the 2-year follow-up compared with participants with no limitation at baseline, whereas the risk among those with minor limitation at baseline was 14- to 18-fold higher compared with those with no limitation. CONCLUSIONS: The self-report assessment tool proved to be a valid measure to capture the early signs of disability and may serve as an inexpensive tool for identifying those nondisabled persons at high risk for future disability.