Major-locus contributions to variability of the craniofacial feature dystopia canthorum in Waardenburg syndrome.

We used segregation analysis to investigate the genetic basis of variation in dystopia canthorum, one of the key diagnostic features of Waardenburg syndrome type 1 (WS1). We sought to determine whether the W-index, a quantitative measure of this craniofacial feature, is influenced primarily either by allelic variation in the PAX3 disease gene or other major loci, by polygenic background effects, or by all of these potential sources of genetic variation. We studied both WS1-affected individuals and their WS1-unaffected relatives. After adjustment of the W-index for WS1 disease status, segregation analyses by the regression approach indicated major-locus control of this variation, although residual parent-offspring and sib-sib correlations are consistent with additional (possibly polygenic) effects. Separate analyses of WS1-affected and WS1-unaffected individuals suggest that epistatic interactions between disease alleles at the PAX3 WS1 locus and a second major locus influence variation in dystopia canthorum. Our approach should be applicable for assessing the genetic architecture of variation associated with other genetic diseases.     

Heterogeneity in Waardenburg syndrome.

Heterogeneity of Waardenburg syndrome is demonstrated in a review of 1,285 patients from the literature and 34 previously unreported patients in five families in the Netherlands. The syndrome seems to consist of two genetically distinct entities that can be differentiated clinically: type I, Waardenburg syndrome with dystopia canthorum; and type II, Waardenburg syndrome without dystopia canthorum. Both types have an autosomal dominant mode of inheritance. The incidence of bilateral deafness in the two types of the syndrome was found in one-fourth with type I and about half of the patients with type II. This difference has important consequences for genetic counseling.     

Waardenburg's Syndrome and Heterochromia Iridum in a Deaf School Population

Waardenburg''s syndrome consists of lateral displacement of the inner canthi of the eyes (dystopia canthorum), a broad nasal root and confluent eyebrows, heterochromia iridum, a white forelock and congenital deafness. The syndrome is inherited as a dominant, but affected individuals do not necessarily have all of the characteristics cited.Five hundred and fourteen pupils at a school for the deaf were screened for features of this syndrome. Three cases were discovered. Eleven other deaf children were found to have heterochromia iridum and two more had white forelocks. The interocular dimensions of the remaining children were recorded as standards by which to judge the presence of dystopia canthorum. The results of chromosomal analysis in two cases with Waardenburg''s syndrome were normal.The findings provide further evidence that Waardenburg''s syndrome is a distinct entity and call in question Mackenzie''s concept of a comprehensive “first arch syndrome”.     

Balanced auricular reconstruction in dystopic microtia with the presence of the external auditory canal

This article presents a new repositioning method in dystopic microtia (low-set microtia, anteriorly tilted microtia, or both) with the presence of the external auditory canal. In the case of low-set malformations, the dystopic auricular canal complex was freed from adjacent bony structure, shifted upward, and anchored to the thick periosteum of the suprameatal triangle or the adjacent superior portion of the temporal bone with nonabsorbable sutures. When the auricular vestige was large and dystopia was severe, the complex was shifted with attachment of the temporoparietal fascia on its cranial part. Meanwhile, when the auricular vestige was small and dystopia was mild, the complex was shifted without attachment of the temporoparietal fascia. Then, the ear framework fabricated with autogenous costal cartilage was positioned and wrapped with the temporoparietal fascial flap. In the case of anteriorly tilted malformations, the dystopic complex was freed, shifted posteriorly, and anchored to the periosteum of the suprameatal triangle. Preauricular dead space, resulting from shifting the complex, was obliterated with pieces of costal cartilage. Simultaneously, the ear framework was placed and wrapped with the temporoparietal fascial flap. No skin necrosis of the shifted complexes occurred in any of the cases. In one case, the facial nerve was transected during dissection and reanastomosed. Upward repositioning distances in low-set microtias were between 1 and 3.5 cm. Posteriorly repositioning distances in anteriorly tilted microtias were 2 and 3 cm. Thirteen patients with low-set malformations, two patients with anteriorly tilted malformations, and three patients with low-set and anteriorly tilted malformations underwent reconstructive operations. The new repositioning method is relatively simple, safe, and effective.     

Locus Heterogeneity for Waardenburg Syndrome is Predictive of Clinical Subtypes

Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I (WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between −2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3.     

Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I).

Waardenburg syndrome type I (WS-I) is an autosomal dominant disorder characterized by sensorineural hearing loss, dystopia canthorum, pigmentary disturbances, and other developmental defects. Klein-Waardenburg syndrome (WS-III) is a disorder with many of the same characteristics as WS-I and includes musculoskeletal abnormalities. We have recently reported the identification and characterization of one of the first gene defects, in the human PAX3 gene, which causes WS-I. PAX3 is a DNA-binding protein that contains a structural motif known as the paired domain and is believed to regulate the expression of other genes. In this report we describe two new mutations, in the human PAX3 gene, that are associated with WS. One mutation was found in a family with WS-I, while the other mutation was found in a family with WS-III. Both mutations were in the highly conserved paired domain of the human PAX3 gene and are similar to other mutations that cause WS. The results indicate that mutations in the PAX3 gene can cause both WS-I and WS-III.     

Chronic constipation recognized as a sign of a SOX10 mutation in a patient with Waardenburg syndrome

Waardenburg syndrome is characterized by hearing loss, pigmentation abnormalities, dysmorphologic features, and neurological phenotypes. Waardenburg syndrome consists of four distinct subtypes, and SOX10 mutations have been identified in type II and type IV. Type IV differs from type II owing to the presence of Hirschsprung disease. We identified a de novo nonsense mutation in SOX10 (p.G39X) in a female pediatric patient with Waardenburg syndrome with heterochromia iridis, profound bilateral sensorineural hearing loss, inner ear malformations, and overall hypopigmentation of the hair without dystopia canthorum. This patient has experienced chronic constipation since she was a neonate, but anorectal manometry showed a normal anorectal reflex. Chronic constipation in this patient was likely to be a consequence of a mild intestinal disorder owing to the SOX10 mutation, and this patient was considered to have a clinical phenotype intermediate between type II and type IV of the syndrome. Chronic constipation may be recognized as indicative of a SOX10 mutation in patients with Waardenburg syndrome.     

Homozygosity for Waardenburg syndrome.

In a large kindred including many individuals affected with Waardenburg (WS) type 1 (WS1) syndrome, a child affected with a very severe form of WS type 3 was born. This child presented with dystopia canthorum, partial albinism, and very severe upper-limb defects. His parents were first cousins, both affected with a mild form of WS1. Molecular analysis of PAX3, the gene that was determined by linkage to cause the disorder in the family, demonstrated a novel missense mutation (S84F) in exon 2 of PAX3 within the paired box. While individuals affected with WS1 were heterozygous for the mutation, the child with WS3 was homozygous for S84F. The observation that the PAX3 homozygote in humans may allow life at least in early infancy and does not cause neural tube defects was unexpected, since, in all the mutations known in mice (splotch), homozygosity has led to severe neural tube defects and intrauterine or neonatal death.     

Correlation between Waardenburg syndrome phenotype and genotype in a population of individuals with identified PAX3 mutations

Waardenburg syndrome (WS) type 1 is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmentary abnormalities of the eye, hair, and skin, and dystopia canthorum. The phenotype is variable and affected individuals may exhibit only one or a combination of several of the associated features. To assess the relationship between phenotype and gene defect, clinical and genotype data on 48 families (271 WS individuals) collected by members of the Waardenburg Consortium were pooled. Forty-two unique mutations in the PAX3 gene, previously identified in these families, were grouped in five mutation categories: amino acid (AA) substitution in the paired domain, AA substitution in the homeodomain, deletion of the Ser-Thr-Pro-rich region, deletion of the homeodomain and the Ser-Thr-Pro-rich region, and deletion of the entire gene. These mutation classes are based on the structure of the PAX3 gene and were chosen to group mutations predicted to have similar defects in the gene product. Association between mutation class and the presence of hearing loss, eye pigment abnormality, skin hypopigmentation, or white forelock was evaluated using generalized estimating equations, which allowed for incorporation of a correlation structure that accounts for potential similarity among members of the same family. Odds for the presence of eye pigment abnormality, white forelock, and skin hypopigmentation were 2, 8, and 5 times greater, respectively, for individuals with deletions of the homeodomain and the Pro-Ser-Thr-rich region compared to individuals with an AA substitution in the homeodomain. Odds ratios that differ significantly from 1.0 for these traits may indicate that the gene products resulting from different classes of mutations act differently in the expression of WS. Although a suggestive association was detected for hearing loss with an odds ratio of 2.6 for AA substitution in the paired domain compared with AA substitution in the homeodomain, this odds ratio did not differ significantly from 1.0. Received: 27 July 1997 / Accepted: 9 December 1997     

Biometric sex discrimination is unreliable when sexual dimorphism varies within and between years: an example in Eurasian Oystercatchers Haematopus ostralegus

Molecular sexing of birds has been possible for over a decade, but for practical reasons many studies still use biometric data for sex discrimination. In some species, the sexes are easy to distinguish but sexual dimorphism is often more subtle, requiring the use of statistical analyses of biometric measurements to discriminate sexes. These models are usually parameterized and validated using data from a limited number of sites and years. However, the resulting discriminant functions are often applied to other populations and periods. A crucial, but usually untested, assumption is that sexual dimorphism does not vary in time and space. Here we illustrate the consequences of violation of this assumption in Eurasian Oystercatchers Haematopus ostralegus , a species for which most studies have relied on biometric sexing. Using biometric data from captures of known-sex birds, we show that sexual dimorphism varied substantially in time and even reversed in some months and years. Furthermore, some biometric traits used in sexing changed gradually over time, causing a reduction in sexual dimorphism. We show that the consequences of this variation on sex discrimination in Oystercatchers are subtle and easily overlooked, but can result in inaccurate and strongly male- or female-biased sex-ratio estimates. We recommend that biometric sexing should be avoided in Oystercatchers unless specific calibration for each month, year and area is carried out. This recommendation also applies to other species where biometric traits may depend on environmental conditions. We argue that this condition might apply to many bird species and therefore advise caution when interpreting results based on biometric sex discrimination.     

The value of MLPA in Waardenburg syndrome

Waardenburg syndrome (WS) is an autosomal-dominant neurocristopathy characterized by sensorineural hearing loss, pigmentary abnormalities of the iris, hair, and skin, and is responsible for about 3% of congenital hearing loss. Point mutations in PAX3 have been identified in more than 90% of affected individuals with WS Type 1/WS Type 3. MITF point mutations have been identified in 10-15% of individuals affected with WS Type 2 (lacking dystopia canthorum). Multiplex ligation-dependent probe amplification (MLPA) is now a standard technology in the molecular genetics laboratory to detect copy number changes in targeted genes. We employed MLPA for PAX3 and MITF in a cohort of patients submitted with a diagnosis of WS1, 2 or 3 who were sequence negative for PAX3 and/or MITF. All coding exons of PAX3 and exons 1, 2, 3, and 10 of MITF were included in the MLPA assay. MLPA on 48 patients with WS 1 or 3 revealed 3 PAX3 whole gene deletions (2 WS1; 1 WS3), 2 PAX3 partial gene deletions [WS1, exon 1 and promoter (1st report); WS1, exons 5-9], and 1 partial MITF deletion ("WS1", exons 3-10) (6/48 approximately 12.5%). MLPA on 41 patients with WS2 and 20 patients submitted with a diagnosis of either WS1 or WS2 revealed no copy number changes. The detection of both partial and whole gene deletions of PAX3/MITF in this clinical cohort increases the mutation detection yield by at least 6% and supports integrating MLPA into clinical molecular testing primarily for patients with WS1 and 3.     

Hemoglobin: normal values

Hematologists are not in agreement as to the "normal" amount of hemoglobin in the blood, nor is there agreement as to what amount of hemoglobin can be considered "a hemoglobin value of 100 per cent." Different hospitals base reports of hemoglobin on different standards, which obviously can be misleading. By biometric study of the great mass of data on hemoglobin content that has become available as a result of the blood procurement program, it should be possible to determine what "normal" values are and to provide a basis for uniformity in reporting.     

Applications of deep convolutional neural networks to predict length,circumference, and weight from mostly dewatered images of fish

Simple biometric data of fish aid fishery management tasks such as monitoring the structure of fish populations and regulating recreational harvest. While these data are foundational to fishery research and management, the collection of length and weight data through physical handling of the fish is challenging as it is time consuming for personnel and can be stressful for the fish. Recent advances in imaging technology and machine learning now offer alternatives for capturing biometric data. To investigate the potential of deep convolutional neural networks to predict biometric data, several regressors were trained and evaluated on data stemming from the FishL? Recognition System and manual measurements of length, girth, and weight. The dataset consisted of 694 fish from 22 different species common to Laurentian Great Lakes. Even with such a diverse dataset and variety of presentations by the fish, the regressors proved to be robust and achieved competitive mean percent errors in the range of 5.5 to 7.6% for length and girth on an evaluation dataset. Potential applications of this work could increase the efficiency and accuracy of routine survey work by fishery professionals and provide a means for longer‐term automated collection of fish biometric data.     

Sensitivity in metric scaling and analysis of distance

Assessing the sensitivity or sampling variability of multivariate ordination methods is essential if inferences are to be drawn from the analysis, but such assessment has to date been notably absent in many applications of multidimensional scaling (MDS). The only available technique seems to be the one by DeLeeuw and Meulman who proposed a special jackknife in a general MDS setting, but this method does not appear to have been widely used to date. A possible reason for this is that it is perceived to be computationally daunting. However, if attention is focused on classical metric scaling (principal coordinate analysis) then known analytical results can be used and the apparent computational complexity disappears. The purpose of this article is to set out these results, to indicate their use in more general analysis of distance, and to illustrate the methodology on some biometric examples.     

Comparison of biometric data of children with high and low levels of lead in the blood

This paper deals with a biometric study of 312 boys and girls, aged 2.5-16 years, living in an area with a long history of pollution by lead. The aim was to search for eventual relationships between ten biometric variables and measures of lead absorption in the bodies, i.e. the amount of lead in the blood (PbB), of these children. Standardized values of the biometric variables were compared in the high-PbB and low-PbB categories, by multivariate analysis of variance. Comparison of the vectors of the ten biometric variables reveals a significant difference between the two categories of PbB levels. We found some evidence that the younger children (below 8 years of age) are more likely to absorb lead in the body and are more vulnerable to the effects of subclinical lead intoxication than their older counterparts. The differences between the averages of biometric variables in the two PbB categories are consistently (although not significantly) greater among younger children. This trend disappeared in the older age group. These results confirm data from the literature that young children are especially at risk. It can be concluded that there is a subtle, but significant, influence of lead absorption on the biometric profiles of children and that this effect is probably more important in children below 8 years of age.     

Two-stage biometric authentication method using thought activity brain waves

Brain waves are proposed as a biometric for verification of the identities of individuals in a small group. The approach is based on a novel two-stage biometric authentication method that minimizes both false accept error (FAE) and false reject error (FRE). These brain waves (or electroencephalogram (EEG) signals) are recorded while the user performs either one or several thought activities. As different individuals have different thought processes, this idea would be appropriate for individual authentication. In this study, autoregressive coefficients, channel spectral powers, inter-hemispheric channel spectral power differences, inter-hemispheric channel linear complexity and non-linear complexity (approximate entropy) values were used as EEG features by the two-stage authentication method with a modified four fold cross validation procedure. The results indicated that perfect accuracy was obtained, i.e. the FRE and FAE were both zero when the proposed method was tested on five subjects using certain thought activities. This initial study has shown that the combination of the two-stage authentication method with EEG features from thought activities has good potential as a biometric as it is highly resistant to fraud. However, this is only a pilot type of study and further extensive research with more subjects would be necessary to establish the suitability of the proposed method for biometric applications.     

One-stage repair of blepharophimosis

Congenital blepharophimosis is a congenital anomaly characterized by abnormalities in the area of the eyes, including bilateral ptosis, shortening of the horizontal fissure of the lid, expansion of the intercanthal distance, and epicanthus inversus. The condition is subject to autosomal-dominant heredity and is said to occur more frequently in Orientals than in Occidentals. Over the past 9 years, we have surgically treated 11 cases of congenital blepharophimosis using a procedure in which levator resection and medial canthoplasty are performed in one stage. It has been commonly believed that when levator resection and medial canthoplasty are performed at the same time, tension in the eyelid becomes too strong to achieve favorable results; therefore, the standard procedure has been to divide the operation into two stages. In all 11 cases we experienced, however, it was possible to obtain good results with a single-stage operation.     

Phenotypic analysis of adults and eggs of Fasciola hepatica by computer image analysis system

Knowledge of the morphological phenotypes of the liver fluke Fasciola hepatica (Trematoda: Digenea) is analysed. The influence of parasite age on its dimensions, the adult fluke growth model, variation in a biometric variable versus time, and variation in a biometric variable versus another biometric variable (allometric model) are revised. The most useful allometric model appears to be (y2 m-y2)/y2=c [(y1 m-y1)/y1](b), where y1=body area or body length, y2=one of the measurements analysed, y1 m, y2 m=maximum values towards which y1 and y2, respectively, tend, and c, b=constants. A method based on material standardization, the measurement proposal and allometric analysis is detailed. A computer image analysis system (CIAS), which includes a colour video-camera connected to a stereomicroscope (for adult studies) and a microscope (for egg studies), facilitates the processing of digital imaging. Examples of its application for the analysis of the influence of different factors on the liver fluke phenotype are shown using material from the Northern Bolivian Altiplano, where human and domestic animal fascioliasis is caused by F. hepatica only. Comparisons between the development of livestock fluke populations from highlands and lowlands are discussed and the relationships between host species and liver fluke morphometric patterns is analysed.     

HEMOGLOBIN: NORMAL VALUES

Hematologists are not in agreement as to the “normal” amount of hemoglobin in the blood, nor is there agreement as to what amount of hemoglobin can be considered “a hemoglobin value of 100 per cent.” Different hospitals base reports of hemoglobin on different standards, which obviously can be misleading.By biometric study of the great mass of data on hemoglobin content that has become available as a result of the blood procurement program, it should be possible to determine what “normal” values are and to provide a basis for uniformity in reporting.     

Taxonomie, écologie et lutte biologique

Summary It is impossible to study modern taxonomy without taking into consideration the population genetic and ecology. Thé Linnean concept of monotypic species should be replaced by the biometric study of the frequency of the variability of the biological characters (particularly morphological) used in taxonomy. The study of populations offers a larger scientific interest than the one of isolated types. It gives the possibility of caracterizing the evolution stability of the species. So, Taxonomy can help considerably in biological control. By revealing large variability species, it gives a criterion of their adjusting plasticity. But, by definition, the biological control is based on the adjusting capacity of the entomophagous insects either to a new host or to a new environment. Information given by the taxonomist on the species stability has consequently a great value in the choice and use of the Entomophagous insects. — Ecologists using biological control, expect from the taxonomist to lie more than a label, which implies the use of biometric analysis methods in Entomophagous taxonomy.