IL11RA-related Crouzon-like autosomal recessive craniosynostosis in 10 new patients: Resemblances and differences.

By describing 10 new patients recruited in centres for Human Genetics, we further delineate the clinical spectrum of a Crouzon-like craniosynostosis disorder, officially termed craniosynostosis and dental anomalies (MIM614188). Singularly, it is inherited according to an autosomal recessive mode of inheritance. We identified six missense mutations in IL11RA, a gene encoding the alpha subunit of interleukin 11 receptor, 4 of them being novel, including 2 in the Ig-like C2-type domain. A subset of patients had an associated connective tissue disorder with joint hypermobility and intervertebral discs fragility. A smaller number of teeth anomalies than that previously reported in the two large series of patients evaluated in dental institutes points toward an ascertainment bias.

Wiedemann-Steiner syndrome as a major cause of syndromic intellectual disability: A study of 33 French cases.

Wiedemann-Steiner syndrome (WSS) is a rare syndromic condition in which intellectual disability (ID) is associated with hypertrichosis cubiti, short stature, and characteristic facies. Following the identification of the causative gene (KMT2A) in 2012, only 31 cases of WSS have been described precisely in the literature. We report on 33 French individuals with a KMT2A mutation confirmed by targeted gene sequencing, high-throughput sequencing or exome sequencing. Patients' molecular and clinical features were recorded and compared with the literature data. On the molecular level, we found 29 novel mutations. We observed autosomal dominant transmission of WSS in 3 families and mosaicism in one family. Clinically, we observed a broad phenotypic spectrum with regard to ID (mild to severe), the facies (typical or not of WSS) and associated malformations (bone, cerebral, renal, cardiac and ophthalmological anomalies). Hypertrichosis cubiti that was supposed to be pathognomonic in the literature was found only in 61% of our cases. This is the largest series of WSS cases yet described to date. A majority of patients exhibited suggestive features, but others were less characteristic, only identified by molecular diagnosis. The prevalence of WSS was higher than expected in patients with ID, suggesting than KMT2A is a major gene in ID.

Molecular, clinical and neuropsychological study in 31 patients with Kabuki syndrome and KMT2D mutations.

Kabuki syndrome (KS-OMIM 147920) is a rare developmental disease characterized by the association of multiple congenital anomalies and intellectual disability. This study aimed to investigate intellectual performance in children with KS and link the performance to several clinical features and molecular data. We recruited 31 children with KMT2D mutations who were 6 to 16 years old. They all completed the Weschler Intelligence Scale for Children, fourth edition. We calculated all indexes: the Full Scale Intellectual Quotient (FSIQ), Verbal Comprehension Index (VCI), Perceptive Reasoning Index (PRI), Processing Speed Index (PSI), and Working Memory Index (WMI). In addition, molecular data and several clinical symptoms were studied. FSIQ and VCI scores were 10 points lower for patients with a truncating mutation than other types of mutations. In addition, scores for FSIQ, VCI and PRI were lower for children with visual impairment than normal vision. We also identified a discrepancy in indexes characterized by high WMI and VCI and low PRI and PSI. We emphasize the importance of early identification and intensive care of visual disorders in patients with KS and recommend individual assessment of intellectual profile.

Genetic counselling difficulties and ethical implications of incidental findings from array-CGH: a 7-year national survey.

Microarray-based comparative genomic hybridization (aCGH) is commonly used in diagnosing patients with intellectual disability (ID) with or without congenital malformation. Because aCGH interrogates with the whole genome, there is a risk of being confronted with incidental findings (IF). In order to anticipate the ethical issues of IF with the generalization of new genome-wide analysis technologies, we questioned French clinicians and cytogeneticists about the situations they have faced regarding IF from aCGH. Sixty-five IF were reported. Forty corresponded to autosomal dominant diseases with incomplete penetrance, 7 to autosomal dominant diseases with complete penetrance, 14 to X-linked diseases, and 4 were heterozygotes for autosomal recessive diseases with a high prevalence of heterozygotes in the population. Therapeutic/preventive measures or genetic counselling could be argued for all cases except four. These four IF were intentionally not returned to the patients. Clinicians reported difficulties in returning the results in 29% of the cases, mainly when the question of IF had not been anticipated. Indeed, at the time of the investigation, only 48% of the clinicians used consents mentioning the risk of IF. With the emergence of new technologies, there is a need to report such national experiences; they show the importance of pre-test information on IF.

[Workplace Health Promotion in Small, Medium-Sized and Large Enterprises of the Health-Care Sector - Frequency, Reasons for the Company Management to Take Action and Barriers to Implementation]. / Betriebliche Gesundheitsförderung in kleinen, mittleren und großen Unternehmen des Gesundheitssektors - Häufigkeit, Handlungsgründe der Unternehmensleitungen und Hürden der Realisierung.

PURPOSE: The aim of this study was to gain insight into worksite health promotion in small and medium-sized companies compared to large concerns in Middle Franconia. Action in worksite health promotion, obstacles and demand for networks for workplace health promotion were determined. METHOD: A standardised telephone interview served for collecting data for this cross-sectional study. The interviewee was always the manager or their proxy. 106 companies were contacted. The results of this study were analysed via qualitative and quantitative methods in SPSS(®) 20. RESULTS: It was possible to reach and interview 80 companies, a return rate of 75.5%. More than half the companies (68.8%) implemented at least one activity for worksite health promotion, especially ergonomic measures and measures to promote physical activity. Taking the size of the company into consideration when analysing the results, previous study results are confirmed. With an increasing size of the company, the relative frequency of measures for workplace health promotion rises. The motivation for worksite health promotion ranges from keeping the employees healthy (38.2%) to worksite health promotion as part of the business culture (9.1%). 81.1% of the companies consider their activity in worksite health promotion to be successful. Furthermore, 80.0% of the firms that implemented worksite health promotion were supported by a partner like a health insurance (43.2%). Those companies that did not implement any activities for worksite health promotion, state as a prime reason that they did not think about it as yet (44.0%). Besides, 44.0% of the companies without any worksite health promotion would like to implement measures. 65.5% of the companies that already took action in worksite health promotion and 56.0% of the companies that did not would like to cooperate with other firms in a network for workplace health promotion. Mutual exchange is the most important factor for them. CONCLUSION: The results of this study show that almost half of the companies that did not implement measures for worksite health promotion as yet would like to take action in this regard. For a bigger establishment of worksite health promotion, networks are predestinated and are best accompanied and supported by external professionals like health insurances, mutual indemnity associations or universities.

Mesoaxial polydactyly is a major feature in Bardet-Biedl syndrome patients with LZTFL1 (BBS17) mutations.

Ciliopathies are heterogeneous disorders sharing different clinical signs due to a defect at the level of the primary cilia/centrosome complex. Postaxial polydactyly is frequently reported in ciliopathies, especially in Bardet-Biedl syndrome (BBS). Clinical features and genetic results observed in a pair of dizygotic twins with BBS are reported. The following manifestations were present: retinitis pigmentosa, bilateral insertional polydactyly, cognitive impairment and renal dysfunction. X-rays of the hands confirmed the presence of a 4th mesoaxial extra-digit with Y-shaped metacarpal bones. The sequencing of LZTFL1 identified a missense mutation (NM_020347.2: p.Leu87Pro; c.260T>C) and a nonsense mutation (p.Glu260*; c.778G>T), establishing a compound heterozygous status for the twins. A major decrease of LZTFL1 transcript and protein was observed in the patient's fibroblasts. This is the second report of LZTFL1 mutations in BBS patients confirming LZTFL1 as a BBS gene. Interestingly, the only two families reported in literature thus far with LZTFL1 mutations have in common mesoaxial polydactyly, a very uncommon feature for BBS. This special subtype of polydactyly in BBS patients is easily identified on clinical examination and prompts for priority sequencing of LZTFL1 (BBS17).

Early intensive care unit-acquired hypernatremia in severe sepsis patients receiving 0.9% saline fluid resuscitation.

BACKGROUND: Intensive care unit (ICU)-acquired hypernatremia is associated with increased mortality and ascribed to excessive sodium/insufficient free water intakes. We aimed to determine whether the volume of intravenous 0.9% saline fluid resuscitation was associated with hypernatremia in severe sepsis. METHODS: We retrospectively reviewed the charts of patients admitted to our medical ICU over 1 year with severe sepsis, and recorded all fluid intakes and plasma sodium levels (Nap ) for 5 days along with clinical data. ΔNap was defined as the difference between maximal Nap reached and initial Nap . Hypernatremia was defined as Nap > 145 mmoles/l. RESULTS: Among 95 patients with severe sepsis, 29 developed hypernatremia within 5 days (31%), reaching a maximum Nap of 149.1 ± 2.5 mmoles/l on average 3.8 ± 1.5 days after admission. For every 50-ml/kg increase in 0.9% saline intake for the first 48 h, the odds of hypernatremia were 1.61 times larger [confidence interval (CI): 0.98-2.62; P = 0.06] and the mean of ΔNap increased by 1.86 mmoles/l (CI: 0.86-2.86; P < 0.001). Compared with non-hypernatremic patients, hypernatremic patients received more 0.9% saline within the first 48 h (111 ± 50 ml/kg vs. 92 ± 42 ml/kg, P < 0.05) and more other fluids from 48 to 96 h (64 ± 38 ml/kg vs. 42 ± 24 ml/kg, P < 0.05). Patients developing hypernatremia had increased length of mechanical ventilation (12.0 ± 12.6 vs. 9.1 ± 7.2 days, P < 0.05) and ICU mortality (38.5% vs. 13%, P < 0.01). CONCLUSIONS: Early acquired hypernatremia is a frequent complication in severe sepsis patients and is associated with the volume of 0.9% saline received during the first 48 h of admission.

Comparison of hematologic variables among Warmbloods, Thoroughbreds, and Western stock horse breeds.

BACKGROUND: Hematology is a diagnostic tool used to evaluate the health status of horses. However, breed differences are often not considered. OBJECTIVES: The objective was to compare complete blood count variables among Warmbloods, Thoroughbreds, and stock horses (SH). METHODS: Ninety-six healthy horses were grouped by breed (Warmbloods, Thoroughbreds, and SH). Samples were collected through venipuncture for complete blood count analysis. One-way ANOVA with Tukey's tests or Kruskal-Wallis with Dunn's post hoc tests were used to compare hematologic variables among groups. RESULTS: Warmbloods had a significantly lower total white blood cell (WBC) count (6.08 ± 1.11 × 109/L) and lymphocyte count (1.76 ± 0.41 × 109/L) than Thoroughbreds (7.28 ± 1.45; 2.28 ± 5.16 × 109/L, respectively; P < .001) and SH (7.21 ± 1.18 × 109/L, P < .01; 2.10 ± 5.17 × 109/L; P < .05). Warmbloods had a significantly lower red blood cell count (7.7 ± 0.8 × 1012/L) and higher mean corpuscular volume (MCV, 49.4 ± 2.2 fL) than Thoroughbreds (8.42 ± 1.2 × 1012/L, P < .01; 47.3 ± 3.0 fL). Warmbloods had lower MCVs than SH (49.4 ± 2.2 vs 51.2 ± 2.6 fL). The mean cell hemoglobin concentration (MCHC) was higher in Warmbloods (35.0, 33.8-36.2 g/dL) and Thoroughbreds (34.9, 33.4-35.7 g/dL) than in SH breeds (34.0, 33.4-35.4 g/dL; P < .001, both). Total protein concentrations were significantly lower in Thoroughbreds (67, 59-80 g/L) compared with SH (71, 64-83 g/dL) (P < .05). CONCLUSIONS: Warmbloods had decreased WBC and lymphocyte counts compared with Thoroughbreds and SH, and Thoroughbreds had increased red blood cell counts. Thoroughbreds had lower total protein concentrations than SH. Clinicians should consider breed differences when interpreting hematologic values.

Plasma proprotein convertase subtilisin kexin type 9 levels are related to markers of cholesterol synthesis in familial combined hyperlipidemia.

BACKGROUND AND AIMS: Two recent independent studies showed that patients with familial combined hyperlipidemia (FCHL) have elevated plasma levels of proprotein convertase subtilisin kexin type 9 (PCSK9) and markers of cholesterol synthesis. Both PCSK9 expression and cholesterol synthesis are downstream effects of hepatic activation of sterol regulatory element binding protein 2 (SREBP2). The present study was conducted to study the relationship between plasma PCSK9 and markers of cholesterol synthesis in FCHL. METHODS AND RESULTS: Markers of cholesterol synthesis (squalene, desmosterol, lathosterol), cholesterol absorption (campesterol, sitosterol, cholestanol) and PCSK9 were measured in plasma of FCHL patients (n = 103) and their normolipidemic relatives (NLR; n = 240). Plasma PCSK9, lathosterol and desmosterol levels were higher in FCHL patients than their NLR (p < 0.001, age and sex adjusted). Heritability calculations demonstrated that 35% of the variance in PCSK9 levels could be explained by additive genetic effects (p < 0.001). Significant age- and sex-adjusted correlations were observed for the relationship between PCSK9 and lathosterol, both unadjusted and adjusted for cholesterol, in the overall FCHL population (both p < 0.001). Multivariate regression analyses, with PCSK9 as the dependent variable, showed that the regression coefficient for FCHL status decreased by 25% (from 0.8 to 0.6) when lathosterol was included. Nevertheless, FCHL status remained an independent contributor to plasma PCSK9 (p < 0.001). CONCLUSIONS: The present study confirms the previously reported high and heritable PCSK9 levels in FCHL patients. Furthermore, we now show that high PCSK9 levels are, in part, explained by plasma lathosterol, suggesting that SREBP2 activation partly accounts for elevated PCSK9 levels in FCHL.

Postnatal phenotype according to prenatal ultrasound features of Noonan syndrome: a retrospective study of 28 cases.

OBJECTIVE: Noonan syndrome is a frequent genetic disorder with autosomal dominant transmission. Classically, it combines postnatal growth restriction with dysmorphic and malformation syndromes that vary widely in expressivity. Lymphatic dysplasia induced during the embryonic stage might interfere with tissue migration. Our hypothesis is that the earlier the edema, the more severe postnatal phenotype. METHOD: This retrospective study analyzed data from all 32 cases of Noonan syndrome diagnosed in the Medical Genetics Department of Hautepierre Hospital in Strasbourg, France, between 1995 and 2011. The postnatal evolution of Noonan syndrome was compared according to the presence of at least one prenatal ultrasound feature of lymphatic dysplasia. RESULTS: The most frequent prenatal ultrasound features found were increased nuchal translucency, cystic hygroma and polyhydramnios; their global prevalence was 46.4%. The presence of these features was not significantly associated with the postnatal phenotype of Noonan syndrome. CONCLUSION: The results of our study indicate that prenatal ultrasound features of lymphatic dysplasia do not predict an unfavorable postnatal prognosis for Noonan syndrome.

Utility of glycated albumin for the diagnosis of diabetes mellitus in a Japanese population study: results from the Kyushu and Okinawa Population Study (KOPS).

AIMS/HYPOTHESIS: Glycated albumin is a measure of the mean plasma glucose concentration over approximately 2-3 weeks. We determined reference values for glycated albumin, and assessed its utility for the diagnosis of type 2 diabetes mellitus in the general population. METHODS: We studied 1,575 men and women (mean age, 49.9 years; range, 26-78 years) who participated in a periodic health examination in a suburban Japanese town. HbA(1c) and fasting plasma concentrations of glucose (FPG) and glycated albumin were measured. Participants with FPG ≥ 7.0 mmol/l or HbA(1c) ≥ 6.5% (48 mmol/mol) were diagnosed as having diabetes. In our laboratory, the glycated albumin assay had intra-assay and inter-assay CVs of 1.1% and 1.6%, respectively. RESULTS: Glycated albumin levels were significantly correlated with HbA(1c) levels (r = 0.766, p < 0.001) and FPG (r = 0.706, p < 0.001). The presence of diabetes was significantly higher in participants with glycated albumin levels between 15.0% and 15.9% (five of 276, 1.81%) than in those with glycated albumin <14% (three of 672, 0.45%) (p = 0.037), and was markedly increased in those with a glycated albumin level >16% (58 of 207, 28.0%). Receiver operating characteristic curve analysis indicated that a glycated albumin level of ≥15.5% was optimal for predicting diabetes, with a sensitivity of 83.3% and a specificity of 83.3%. CONCLUSIONS/INTERPRETATION: There is merit to further investigating the potential for glycated albumin to be used as an alternative measure of dysglycaemia for future research and clinical practice.

FAK integrates growth-factor and integrin signals to promote cell migration.

Here we show that cells lacking focal adhesion kinase (FAK) are refractory to motility signals from platelet-derived and epidermal growth factors (PDGF and EGF respectively), and that stable re-expression of FAK rescues these defects. FAK associates with activated PDGF- and EGF-receptor (PDGFR and EGFR) signalling complexes, and expression of the band-4.1-like domain at the FAK amino terminus is sufficient to mediate an interaction with activated EGFR. However, efficient EGF-stimulated cell migration also requires FAK to be targeted, by its carboxy-terminal domain, to sites of integrin-receptor clustering. Although the kinase activity of FAK is not needed to promote PDGF- or EGF-stimulated cell motility, kinase-inactive FAK is transphosphorylated at the indispensable Src-kinase-binding site, FAK Y397, after EGF stimulation of cells. Our results establish that FAK is an important receptor-proximal link between growth-factor-receptor and integrin signalling pathways.

Efficacy and tolerability of two oral hyoscine butylbromide formulations in Chinese patients with recurrent episodes of self-reported gastric or intestinal spasm-like pain.

AIM: To compare the efficacy and tolerability of oral hyoscine butylbromide tablets and capsules in Chinese patients with recurrent episodes of self-reported gastric or intestinal spasm-like pain and to show non-inferiority of both formulations. METHODS: 302 patients were entered into a randomized, double-blind, double-dummy, active-controlled 2-arm parallel group study. They were randomized to 3 days of treatment with hyoscine butylbromide tablets or capsules. In patient diaries the pain intensity was assessed on 10 cm visual analogue scales on Day 1 (0, 30, 60, 90, 120, and 180 minutes after first dose), Days 2, and 3 (maximum pain intensity once daily). Pain frequency, overall efficacy, and tolerability were assessed on verbal rating scales. RESULTS: In the per-protocol dataset 281 patients were analyzed. The change from baseline after 180 minutes was 59% in both treatment groups; the adjusted means of pain intensity on Day 1 were reduced by -2.36 cm (tablets) and -2.31 cm (capsules). Pain intensity decreased within 30 minutes by approximately 20%. The decrease of the peak pain intensity was approximately 55% after 3 days in both treatment groups; the adjusted means after 3 days were reduced by -2.48 cm (tablets) and by -2.45 cm (capsules). Abdominal pain frequency decreased by 50% (tablets) and 42% (capsules). Both treatments were well tolerated. Drug-related adverse events were infrequent (3.5%). No serious adverse event occurred. CONCLUSIONS: Hyoscine butylbromide is effective in the treatment of recurrent gastric or intestinal spasm-like pain and well tolerated. Non-inferiority of tablets and capsules was demonstrated.

Terrestrial toxicity evaluation of decabromodiphenyl ethane on organisms from three trophic levels.

Decabromodiphenyl ethane (DBDP-Ethane) was evaluated for its potential to effect sewage sludge respiration, soil nitrification, survival and reproduction in Eisenia fetida, and seedling emergence and growth in Zea mays, Lolium perenne, Glycine max, Allium cepa, Lycopersicon esculentum, and Cucumis sativa. The no observed effect concentrations (NOECs) were identified at the limit concentration level for sewage sludge respiration (>10 mg DBDP-Ethane/kg dry soil), >2500 mg/kg dry soil for soil nitrification, >3720 mg/kg dry soil for earthworm survival, and >6250 mg/kg dry soil for seedling emergence and growth in Z. mays, L. perenne, and G. max . Treatment-related effects were identified for E. fetida reproduction, C. sativa survival, and L. esculentum and A. cepa height and dry weight. The most sensitive endpoints were decreased height and dry weight for A. cepa and decreased reproduction for E. fetida with NOECs of 1563(nominal) (1540(measured)) and 2210(nominal) (1907(mean measured)) mg/kg dry soil. The NOEC for soil nitrification and the lowest NOEC identified for soil (i.e., A. cepa) were used to derive predicted no effect concentrations (PNEC) values of 2500 mg/kg for sewage sludge and 156 mg/kg for soil. The calculated PNECs indicate DBDP-Ethane presents little risk to organisms in the sewage sludge and soil compartments.

New perspectives on community-acquired pneumonia in 388 406 patients. Results from a nationwide mandatory performance measurement programme in healthcare quality.

BACKGROUND: The database of the German programme for quality in healthcare including data of every hospitalised patient with community-acquired pneumonia (CAP) during a 2-year period (n = 388 406 patients in 2005 and 2006) was analysed. METHODS: End points of the analysis were: (1) incidence; (2) outcome; (3) performance of the CRB-65 (C, mental confusion; R, respiratory rate >or=30/min; B, systolic blood pressure <90 mm Hg or diastolic blood pressure or=65 years) score in predicting death; and (4) lack of ventilatory support as a possible indicator of treatment restrictions. The CRB-65 score was calculated, resulting in three risk classes (RCs). RESULTS: The incidence of hospitalised CAP was 2.75 and 2.96 per 1000 inhabitants/year in 2005 and 2006, respectively, higher for males (3.21 vs 2.52), and strongly age related, with an incidence of 7.65 per 1000 inhabitants/year in patients aged >or=60 years over 2 years. Mortality (13.72% and 14.44%) was higher than reported in previous studies. The CRB-65 RCs accurately predicted death in a three-class pattern (mortality 2.40% in CRB-65 RC 1, 13.43% in CRB-65 RC 2 and 34.39% in CRB-65 RC 3). The first days after admission were consistently associated with the highest risk of death throughout all risk classes. Only a minority of patients who died had received mechanical ventilation during hospitalisation (15.74%). CONCLUSIONS: Hospitalised CAP basically is a condition of the elderly associated with a higher mortality than previously reported. It bears a considerable risk of early mortality, even in low risk patients. CRB-65 is a simple and powerful tool for the assessment of CAP severity. Hospitalised CAP is a frequent terminal event in chronic debilitated patients, and a limitation of treatment escalation is frequently applied.

Type III hyperlipoproteinemia associated with apolipoprotein E deficiency.

Subjects with type III hyperlipoproteinemia develop premature atherosclerosis and have hyperlipidemia due to an increase in cholesterol-rich very low density lipoproteins (VLDL) of abnormal electrophoretic mobility. Apolipoprotein E is a major protein constituent of VLDL and appears to be important for the hepatic uptake of triglyceride-rich lipoproteins. A new kindred of patients with type III hyperlipoproteinemia is described in which no plasma apolipoprotein E could be detected, consistent with the concept that type III hyperlipoproteinemia may be due to an absence or striking deficiency of apolipoprotein E.

Similarity of cruzin, an inhibitor of Trypanosoma cruzi neuraminidase, to high-density lipoprotein.

A specific inhibitor of the neuraminidase of the protozoan parasite Trypanosoma cruzi was isolated recently and named cruzin. It is now shown that cruzin is similar to high-density lipoprotein by amino acid homology, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, by immunoblot analysis, and by isoelectric focusing. Cruzin purified by ion exchange chromatography and high-density lipoprotein isolated by density gradient ultracentrifugation inhibited Trypanosoma cruzi neuraminidase to the same extent. Cruzin or high-density lipoprotein restores to normal the decreased multiplication rate of Trypanosoma cruzi epimastigotes grown in a medium depleted of lipoproteins, suggesting that it may be important for survival of the parasite in nature.

Type III hyperlipoproteinemia: defective metabolism of an abnormal apolipoprotein E.

The apolipoprotein E isolated from plasma of individuals with type III hyperlipoproteinemia (HLP) shows an abnormal pattern when it is examined by isoelectric focusing. Compared to apolipoprotein E from normal subjects, apolipoprotein E isolated from subjects with type III HLP had a decreased fractional catabolic rate in vivo in both type III HLP patients and normal individuals. The delayed catabolism of apolipoprotein E in type III HLP patients may be responsible for the lipid and lipoprotein abnormalities characteristic of these patients.

Distinct hepatic receptors for low density lipoprotein and apolipoprotein E in humans.

Since the liver is a central organ for lipid and lipoprotein synthesis and catabolism, hepatic receptors for specific apolipoproteins on plasma lipoproteins would be expected to modulate lipid and lipoprotein metabolism. The role of hepatic receptors for low density lipoproteins and apolipoprotein E-containing lipoproteins was evaluated in patients with complementary disorders in lipoprotein metabolism: abetalipoproteinemia and homozygous familial hypercholesterolemia. In addition, hepatic membranes from a patient with familial hypercholesterolemia were studied and compared before and after portacaval shunt surgery. The results establish that the human liver has receptors for apolipoproteins B and E. Furthermore, in the human, hepatic receptors for low density lipoproteins and apolipoprotein E are genetically distinct and can undergo independent control.

Silent hemoglobin alpha genes in apes: potential source of thalassemia.

Small quantities of unusual hemoglobins were found in 1 of 37 chimpanzees and 2 of 6 gorillas. In each genus these hemoglobins contain unique alpha chains that differ from the ordinary by eight to nine scattered amino acid changes. The unusual chains arise from a hitherto undetected hemoglobin (3)alpha locus. No (3)alpha products are found in most apes; accordingly, (3)alpha is considered synthetically inactive in all but a few reversion mutants. Indirect evidence that the inactive (3)alpha locus is juxtaposed to an active alpha locus together with the supposition that (3)alpha exists in man provides a setting wherein thalassemia might be produced by nonhomologous recombination between two loci.