bluuebunny/crossref_metadata_2025 huggingface dataset:
“Blind” versus direct vision technique for fetal skin sampling in cases for prenatal diagnosis
Authors: Löfberg Lars , Gustavii Björn
Published: July 2010

Seven fetuses at risk of developing a serious inherited skin disorder (epidermolysis bullosa atrophicans generalisata gravis in 4, bullous ichthyosiform erythroderma in 2, and non‐bullous ichthyosiform erythroderma in 1) were subjected to prenatal diagnosis by fetal skin sampling. The conventional “blind” biopsy procedure was used in the first 3 cases; a two‐cannula technique (one cannula for the optic instrument and the other for the biopsy forceps) that permits biopsy of the skin under direct vision, was employed in the remaining 4 cases. With the “blind” technique, 8 to 10 biopsy specimens had to be taken to ensure that enough skin material would be available for the microscopic examination; only one specimen out of every two was found to consist of skin; the remainder comprised fetal membranes, myometrium, or tro‐phoblast. In one case where the “blind” procedure had been used, leakage of amniotic fluid occurred and labor started in the 33rd week. With the two‐cannula technique, the number of biopsy samples could be confined to two or three, and all proved to be of skin.
Familial balanced insertion (5;10) and monosomy and trisomy (10) (q24.2→q25.3)
Authors: Vooren M. J. van de , Planteydt H. T. , Hagemeijer A. , Peters‐Slough M. F. , Timmerman M. J.
Published: July 2010

The phenotype of a boy with monosomy of a small segment of chromosome (10) (q24.2→q25.3) is described. In his family a balanced insertion (5;10) is found in three generations. Moreover there are two persons who are trisomic for the same small segment of chromosome 10 for which the boy is monosomic.
The level of 6‐phosphogluconate dehydrogenase (6‐PGD) activity in a patient with a 1p terminal deletion suggests that the gene locus is not distal to sub‐band p36.3 on chromosome 1
Authors: Steele M. W. , Wenger S. L. , Geweke L. O. , Golden W. L.
Published: July 2010

A rare case of chromosome 1p deletion is reported in a mentally retarded male infant with a derived chromosome: 45, XY, ‐1, ‐13, tdic(1;13) (1qter → 1p36.2:13p11.2 → 13qter). Parental chromosomes were normal. Since the patient's 6‐PGD specific activity was in the normal range, it is probable that he retained both 6‐PGD alleles. Consequently, if a dosage affect exists, then the locus for 6‐PGD must be proximal to 1p36.3.
Familial minor neurodevelopmental disorders
Authors: Rasmussen F. , Gustavson K.‐H. , Bille B.
Published: July 2010

Sixteen patients (13 males and 3 fcmales) with minor neurodevelopmental disorders from 7 families were examined in an etiologic study. In four of the families (3, 5, 6 and 7) no brain damaging factors could be traced in the prenatal, perinatal or postnatal periods, and genetic main etiologies were strongly suspected. In one family (I) alcohol abuse during the pregnancies was thought to be an etiologically contributing factor. Potentially brain damaging factors were demonstrated in at least one patient from each of the remaining two families (2 and 4), and might, in these cases, have interacted with hereditary factors.
Familial Wolf's syndrome with a hidden 4p deletion by translocation of an 8p segment. Unbalanced inheritance from a maternal translocation (4;8)(p15.3;p22). Case report, review and risk estimates
Authors: Stengel‐Rutkowski S. , Warkotsch A. , Schimanek P. , Stene J.
Published: July 2010

This is the case report of a patient with Wolfs syndrome having a monosomy 4pter→p15.3 and an additional trisomy 8pter→p22, derived from a maternal balanced translocation t(4;8)(p15.3;p22) after 2:2 disjunction and adjacent‐1 segregation. The patient's phenotype is presumably slightly modified by the trisomic 8p segment. Literature analyses indicate that phenotypic “hybrids” with traits of monosomy 4p and of other autosomal segment trisomies exist.

The dermatoglyphics of the patient were not highly characteristic for Wolfs syndrome. Also the dermatoglyphics of the balanced translocation carriers were unspecific and did not reflect the carrier status. Pedigree analyses of 46 reported families with reciprocal translocations involving the short arm of chromosome 4 show a high risk (20.5%±4.6%) for unbalanced offspring (trisomy or monosomy 4p) after 2:2 disjunction and adjacent‐1 segregation, if the breakpoint in the recipient chromosome is terminal and the resulting imbalance concerns the 4p segment only. It is considerably lower (4.5%±2.5%) if the breakpoint in the recipient chromosome is subterminal, as in the reported case, and the resulting imbalance concerns other chromosome segments additionally to the 4p segment. In both instances, the risk decreases with increasing segment length. The risk for unidentified abortions, stillbirths or neonatal deaths is also high in these families (about 40%). The frequency of progeny with balanced compared to progeny with normal karyotype corresponds to the expected 50% for alternate segregation.
Five generations of t(4;8)(q35;q13) leading to a case of partial 8q trisomy with consideration of potential pregnancy outcomes from translocation carriers
Authors: Young Robert S. , Hansen Kathryn L. , Khodr Gabriel S.
Published: July 2010

We describe a female infant with partial trisomy 8q who has rnicrophthalmia, a cleft palate, micrognathia and a heart defect. Her dysmorphogenetic features closely resemble the characteristic pattern seen in the 17 cases thus far reported in the literature. Her chromosomal defect was caused by an unbalanced translocation, inherited through her father, and found to have been transmitted through at least 5 generations. Recently developed models designed to predict the most probable mode of unbalanced segregation from the meiotic quadrivalent and the likelihood that a chromosomally unbalanced fetus will survive to term are applied to this family's translocation. Also, the frequencies of potential reproductive outcomes from carriers of this translocation generated from empiric data are considered as a requisite aid to genetic counseling.
Control of homozygous β‐thalassemia by carrier screening and antenatal diagnosis in Sardinians
Authors: Cao A. , Pintus L. , Lecca U. , Oixa G. , Cossu P. , Rosatelli C. , Galanello R.
Published: July 2010

This paper reports the present results of an ongoing program aimed at preventing homozygous β‐thalassemia by means of heterozygote screening and antenatal diagnosis in the Sardinian population.

Screening based on the knowledge of carrier frequency and types of thalassemia prevalent in this population was designed to discover all heterozygotes except the few silent β‐thalassemia carriers. Most of the couples at risk were informed and accepted testing. Information was conveyed by mass media, midwives and marriage registry offices. Antenatal diagnosis was accepted by the majority of the couples counselled. The results of antenatal testing were very accurate. There was only one misdiagnosis out of 949 pregnancies tested. This risk of fetal loss was 7.5%. The program was highly effective, as shown by the decline of the incidence of the homozygous state from 1:205 live births in 1976 to 1:557 in 1981.
Familial pericentric inversion (14)(p11;q24) with a rec dup(q) in one offspring
Authors: Kaiser P. , Forster W. , Steuernagel P. , Hillig U. , Herberg K.‐P.
Published: July 2010

A new case of pericentric inversion (14) is presented with the breakpoints in pllq24. The same breakpoints have not been described previously. Within the family there is one daughter having a rec(14)dup(q) besides healthy carriers.
Manifestations and natural history of idiopathic hemihypertrophy: a review of eleven cases
Authors: Viljoen D. , Pearn J. , Beighton P.
Published: July 2010

Idiopathic hemihypertrophy is a specific entity which is distinct from the numerous other causes of limb overgrowth. In our investigation of eleven new cases in South Africa and Australia, no genetic or other aetiological factors could be recognised. There were no differences in bone age between the normal and hypertrophied limbs and the pattern of growth through life showed that relative body proportions remained the same. Idiopathic hemihypertrophy is associated with mild mental retardation, genito‐urinary anomalies and an oncogenic potential. Regular clinical surveillance for abdominal tumours is recommended.
The impact of large Y chromosome on pregnancy, foetus and birth
Authors: Videbech P. , Nielsen J. , Wohlert M. , Eriksen G. , Hansen K. B. , Hvidman L. , Krag‐Olsen B.
Published: July 2010

In a current investigation of children born in the Arhus area (Denmark) chromosome examinations were made in6, 691 newborns. Of these children, 170 boys had a large Y chromosome (2.6%). The present material was examined using a bi‐variate stratified analysis to eliminate social and simple biological factors that could act as confounders.

No increased frequency of malformations was found, and birth weight and length was nearly equal in the probands and the controls. A significantly increased frequency of prostaglandin stimulation of labour was found for the mothers of the Yq + boys. Differencies in the frequency of mechanical disproportion or abnormal presentation could not explain this. The Yq + boys suffered more frequently from intrauterine asphyxia leading to acute Caesarean section. This finding cannot be explained by long‐standing placenta problems alone.

A possible mechanism which could link these findings together is suggested, and it is concluded that the boys with Yq + most probably should be regarded as being at a certain risk at the time of birth.
Detection of the fragile X chromosome and other fragile sites
Authors: Hecht Frederick , Sutherland Grant R.
Published: July 2010

To assist in cell sample size selection and detect the fragile X chromosome, statistical tables have been presented. A comparable approach had been suggested earlier for the diagnosis of chromosome mosaicism. The cytologic detection of the fragile X or any fragile site is simply a special case in the detection of mosaicism. Minimum numbers of metaphases are recommended for fragile X analysis to have 95% confidence that the fragile X is not manifest in a given proportion of cells and similar recommendations apply to all other fragile sites.
Usefulness of 4‐methylumbelliferyl‐6‐ sulfo‐2‐acetamido‐2‐deoxy‐β‐D‐glucopyranoside for the diagnosis of GM2 gangliosidoses in leukocytes
Authors: Inui Koji , Wenger David A.
Published: July 2010

4‐Methylumbelliferyl‐6‐sulfo‐2‐acetamido‐2‐deoxy‐β‐D‐glucopyranoside was synthesized and tested as a substrate for the diagnosis of GM2 gangliosidoses using leukocytes. Less than 2% of normal activity was measured in homogenates from patients with typical Tay‐Sachs disease and from a patient with a variant form having 37% Hexosaminidase A by heat denaturation using the usual fluorogenic substrate. An adult patient had 8.5% of normal activity. Three patients with Sandhoff disease were found to have values ranging from 17% to 37% of normal. These values overlap the range found for carriers of Tay‐Sachs disease, and suggest that the usefulness of this substrate, while excellent for diagnosing B variants of GM2 gangliosidosis, requires further study. Perhaps when used together with 4‐methylumbelliferyl‐2‐acetamido‐2‐deoxy‐β‐D‐glucopyranoside excellent discriminations of patients, carriers and controls will be realized.
Fetal mortality in oral cleft families (IX): factors relating to the occurrence of sporadic clefts
Authors: Dronamraju Krishna R. , Wakim Kahlil G. , Smith David J. , Bixler David
Published: July 2010

Pedigree data on 854 probands with cleft lip and/or cleft palate from the State of Indiana are presented. These include 123 probands with cleft lip alone (CL), 453 with cleft lip and palate (CLP), and 278 with isolated cleft palate (CP). Probands and families were interviewed at the Indiana University Medical Center during the years 1962–1980. Among features of special interest are an excess of bilateral CLP (46% of all CLP cases) and a significantly greater number of older mothers and fathers (over 34 years old) than in the general population. An apparent increase in the proportion of sporadic cases with time may be due to bias in ascertainment.

It is suggested that the increased proportions of more severe clefts and older parents are among several factors which contribute to the incidence of fetal mortality in a cleft population. The association of fetal mortality with liability to clefting introduces a more precise way to define a sporadic cleft. That is, a truly sporadic cleft is one conceived as a single occurrence event and has survived to become a liveborn cleft child whereas other apparently sporadic cleft individuals represent the surviving cleft in a sibship in which fetal mortality has eliminated all other cleft offspring already conceived.

This observation has applications to the collection and interpretation of genetic pedigree data for clefts as well as many other genetic conditions.
Early clinical signs in Coffin‐Lowry syndrome
Authors: Vles J. S. H. , Haspeslagh M. , Raes M. M. R. , Fryns J. P. , Casaer P. , Eggermont E.
Published: July 2010

Two unrelated patients with Coffin‐Lowry syndrome are described. The main characteristics of a typical face, thick hands with tapering fingers and a transverse hypothenar crease, general hypotonia with extensible joints made diagnosis possible before the age of 6 months. A persistent large anterior fontanel beyond the age of two years may be another associated finding. Retarded bone age, coarsity of the face and skeletal malformations considered characteristic in adult patients were not present.

Early recognition of Coffin‐Lowry syndrome is important for genetic counseling and prevention of severe skeletal malformations.
X‐linked recessive microencephaly, microphthalmia with corneal opacities, spastic quadriplegia, hypospadias and cryptorchidism
Authors: Siber Margaret
Published: July 2010

Three males in two generations of a family had microencephaly, microphthalmia with corneal opacities, spastic quadriplegia, hypospadias and cryptorchidism. X‐linked recessive inheritance is postulated.
The fragile X syndrome: A study of 83 families
Authors: Fryns J. P.
Published: July 2010

The present report summarizes the experience on the mar(X) syndrome in a total of 157 male patients (44 prepubertal and 113 postpubertal) ascertained through 83 index patients from 83 families under investigation.

1. In one third of the families pedigree data were consistent with X‐linked recessive inheritance. In the further two thirds of the families the presenting symptom was familial mental retardation with a mentally retarded mother, or mental subnormality with hyperkinetic behaviour in the male patient.

2. No more than 60% of the adult males presented the typical clinical triad (mental retardation ‐long face ‐ megalotestes). The most characteristic finding in the mar(X) boy is the psychological profile with severe hyperkinetism, hypersensitivity, handbiting and autistic features in some of them.

3. In 4 of the 27 large mar(X) pedigrees strong evidence was present of a possible transmission of the mar(X) through normal males.

4. The high incidence of mental subnormality in the female offspring of heterozygote carriers, and the relationship between mental status, phenotype, age and expression of the mar(X) in different culture conditions is discussed.
Familial occurrence of azoospermia and extreme oligozoospermia
Authors: Budde Willem J. A. M. , Verjaal Marianne , Hamerlynck Johan V. Th. H. , Bobrow Martin
Published: July 2010

To determine the familial incidence of azoospermia and extreme oligozoospermiak (AEO; sperm counts < 3 106/ml) 147 men with primary AEO were asked, by means of mailed questionnaires, for the occurrence of infertility among their brothers. 119 questionnaires were completed (81 %). Out of a total of 163 informative brothers 7 were reported infertile, of whom 3 had a documented AEO. This incidence is probably about double the general population frequency. A familial case of congenital aplasia of the vasa deferentia was found; this has previously been reported to recur in a sibship and may represent a simple inherited disorder.
Interstitial deletion of the long arm of chromosome 6 [del(6)(q16q22)]: case report and review of the literature
Authors: Schwartz M. F. , Kaffe S. , Wallace S. , Desnick R. J.
Published: July 2010

Partial monosomy of 6q resulting from an interstitial deletion of bands q16 → q22 was found in a 12‐year‐old boy manifesting mental retardation, seizure disorder, and dysmorphic features. The correlation of phenotypic expression and specific long arm deletions of chromosome No. 6 is discussed.
Weyers acrodental dysostosis in a family
Authors: Roubicek Martin , Spranger Jurgen
Published: July 2010

A four generation family with postaxial Polydactyly of hands and feet and dental anomalies is reported. Lower and upper incisors were abnormal in shape and number. Additional findings were prominent ear anthelices, hypoplastic and dysplastic nails and mild shortness of stature. Inheritance was dominant with variable expression. It is proposed that the family presents the syndrome of acrofacial dysostosis described by Weyers in 1952. To differentiate it from other acrofacial dysostoses, we suggest naming the condition acrodental dysostosis.
Frequency of abnormal karyotypes in relation to the ascertainment method in females referred for suspected sex chromosome abnormality
Authors: Anglani Franca , Baccichetti Carlo , Artifoni Lina , Lenzini Elisabetta , Tenconi Romano
Published: July 2010

Cytogenetic investigation was carried out on 231 female patients referred for suspected sex chromosome abnormality. Cases were classified into five groups according to reason for referral and chromosome abnormality frequency was estimated. The overall frequency of abnormal karyotypes was 38.5%. The rate of positive identification of chromosome abnormality ranges from 0 in patients with secondary amenorrhoea to 80% in those with Turner phenotype. Our data demonstrate that the indications for referral of female patients with suspected sex chromosome abnormality are not only primary amenorrhoea alone or short stature and primary amenorrhoea without Turner stigmata, but also short stature of unknown etiology without any additional anomaly during childhood.
Ehlers‐Danlos syndrome type IV D: an autosomal recessive disorder
Authors: Sulh Hassan M. B. , Steinmann Beat , Rao Velidi H. , Dudin Gertrud , Zeid Joseph Abu , Slim Michel , Kaloustian Vazken M. Der
Published: July 2010

Two siblings born to consanguineous parents are reported with typical clinical features of the Ehlers‐Danlos syndrome type IV. However, their cultured skin fibroblasts synthesize and secrete procollagen type III in normal amounts and proportions. This is probably a new form of the Ehlers‐Danlos syndrome with autosomal recessive inheritance classified as Ehlers‐Danlos syndrome type IV D.
Reduced fertility in women with X chromosome abnormality
Authors: Fitzgerald P. H. , Donald R. A. , McCormick P.
Published: July 2010

One patient with the karyotype 46, X, del(X)(p 11.23) and three patients with 45, X/46, XX mosaicism were fertile or showed normal ovarian function. The patient with the Xp deletion has two daughters with the same chromosomal abnormality. A study of these patients and of others reported in the literature indicated that fertility of patients with X chromosomal abnormality has a markedly shorter duration than fertility of the normal female. Menopause commonly occurred during the second and third decade of age. We suggest that such fertility is related to the rate of germ cell attrition and hypothesize that germ cell attrition in the human female is influenced by genes of multiple effect which are carried on the X chromosome. The more of these genes which are present the slower the rate of germ cell attrition.
Cytogenetic and clinical findings in ten 45, X/46, XY patients*
Authors: Ayuso M. C. , Ramos M. C. , Bello M. C. , Jimenez A. , Cascos A. Sanchez , Herrera J. L.
Published: July 2010

We report ten cases with 45, X/46, XY karyotype. Cytogenetic and clinical findings have been compared. No constant relationship was found either between blood and gonadal karyotype, or between karyotype and gonadal morphology.
Duplication or insertion in 15q11–13 associated with mental retardation ‐short stature and obesity ‐ Prader‐Willi or Cohen syndrome?
Authors: Fuhrmann‐Rieger Annemare , Köhler Angelika , Fuhrmann W.
Published: July 2010

Difficulties of differential diagnosis between Prader‐Willi Syndrome and Cohen Syndrome are demonstrated in a 12–year‐old girl with obesity and mental retardation.

Cytogenetic studies showed an apparently supernumerary band on chromosome 15 in the proximal region q11‐13.

Both parents have a normal karyotype.

The aberrant chromosome was derived from an apparently normal paternal chromosome.
Partial Trisomy 9q resulting from a familial translocation t(9;16)(q32;q24)
Authors: Soltan H. C. , Jung J. H. , Pyatt Z. , Singh R. P.
Published: July 2010

Partial Trisomy‐9q was observed in an infant with a multiple malformation syndrome who survived to 18 months. Cytogenetic investigations stimulated by the family history of similarly affected individuals revealed a translocation, t(9;16)(q32;q24), identifiable in four generations of the proband's family. A review of our cases with those reported in the literature reveals clinical similarities. This report sets forth a clinical description of the characteristic phenotype of the 9q partial Trisomy syndrome, including findings at post‐mortem, documents multigeneration transmission and discusses this syndrome's clinical overlap with other malformation syndromes.
Ocular, cerebral and cutaneous malformations: confirmation of an association
Authors: Ferguson James W. , Hutchison H. Terry , Rouse Bobbye M.
Published: July 2010

A newborn with multiple congenital abnormalities including an orbital cyst, cerebral cysts, skin tags and focal dermal defects is described. This case is similar to two patients reported by Delleman & Oorthuys in 1981 under the designation “Oculo‐cerebro‐cutaneous syndrome.” Features common to other syndromes are discussed and additional cases with some similarities are also presented. The occurrence of this process in a new population and the cited variability helps confirm and define this association.
Fragile sites and chromosome breakpoints in constitutional rearrangements I. Amniocentesis
Authors: Hecht Frederick , Hecht Barbara K.
Published: July 2010

Since fragile sites may conceivably predispose to chromosome breakage and rearrangements in meiosis, we examined the locations of 278 breakpoints leading to chromosome rearrangements detected in amniocenteses. Of the 278 breakpoints. 59 (21%) were observed to be in bands containing fragile sites compared to an expectation of 31 (11%), a highly significant difference (P<0.001). The tendency for breakpoints to be in bands with fragile sites was independent of origin of the rearrangement or class of fragile site. consistent with the concept that fragile sites predispose to heritable chromosome rearrangements.
Oro‐facio‐digital syndromes I and II: radiological methods for diagnosis and the clinical variations
Authors: Annerhn G. , Arvidson B. , Gustavson K‐H. , Jorulf H. , Carlsson G.
Published: July 2010

In view of the different modes of inheritance and the different prognoses of the two oro‐facio‐digital syndromes, type 1 (OFD‐I) and type 2 (OFD‐II), it is important to establish a correct diagnosis in these patients.

In this report two new patients with the OFD‐I syndrome are presented. One of them (Case 1) had multiple congenital malformations and never made any mental contact. She died at the age of four months and autopsy of the brain revealed abnormalities typical of the syndrome, which are discussed. The other patient (Case 2) has so far had normal mental development. Although these two patients were affected to a very different degree, they both presented the clinical and radiological characteristics of the OFD‐I syndrome.

These two patients and previously reported cases of the OFD‐I and OFD‐II syndromes were compared with a patient with the OFD‐II syndrome (Case 3), a patient reported earlier who is undergoing follow‐up.

The radiological features of the skeleton in the two syndromes are presented. The irregular mineralization of the hands and feet characteristic of OFD‐I, but not of OFD‐II, seems to offer a good opportunity to distinguish between these two syndromes. It is suggested that this finding is pathognomonic for the OFD‐I syndrome.
Analysis of a familial 15p + polymorphism: exclusion of Y/15 translocation
Authors: Werner W. , Herrmann F. H.
Published: July 2010

A large 15p + chromosome with a whole heterochromatic short arm has been studied by means of different banding techniques in six of nine individuals of a family; a possible Y/15 translocation has been excluded. Furthermore a heteromorphic pair 9 has been observed in seven family members, representing a “possible” small partial inversion 9q12;pll or a centromeric variation. The transmission of these variant chromosomes as well as of some h + acrocentric chromosomes over three generations could be demonstrated. By means of AgI‐staining large intercellular variation of Ag‐NORs of the variant acrocentrics has been observed in the family members studied. The unusual accumulation of these variant chromosomes had no phenotypic effects.
Occurrences of methylmalonic aciduria and Hartnup disorder in the same family
Authors: Shih V. E. , Coulombe J. T. , Wadman S. K. , Duran M. , Waelkens J. J. J.
Published: July 2010

Methylmalonic aciduria and Hartnup disorder are two rare autosomal recessively inherited metabolic disorders. We have described the coexistence of these disorders within the same pedigree in two unrelated families. This assocation was not found in 57 other families surveyed because of a proband known to have either methylmalonic aciduria or Hartnup disorder.
FamiIial vascuIar malformations Report of 25 members of one family
Authors: Pasyk Krystyna A. , Argenta Louis C. , Erickson Robert P.
Published: July 2010

Vascular malformations are described in 25 members of one affected family. Most of these lesions were cavernous hemangiomas, but arteriovenous malformations and capillary heman‐giomas were also microscopically observed in some specimens. The five generation pedigree suggests the vascular malformations are genetically determined on the basis of a dominant inherited trait.
The relative risk for standard 21 trisomy has not increased in young mothers in Belgium, 1960–1978
Authors: Evers‐Kiebooms G. , Vlietinck R. , Berghe H. van den
Published: July 2010

In the present investigation we directly studied the constancy of the relative risks for standard 21 trisomy in Belgium during the period 1960–1978.

The relative risk for standard 21 trisomy in different maternal age‐groups, as compared to 20–24 years and 40–44 years remained remarkably constant during the period under investigation. The increasing percentage of children with standard 21 trisomy born to younger mothers does not result from an increased risk for mothers of this maternal age‐group, but results from the general shift towards a younger maternal age at birth for the total population of births in Belgium.
HLA‐DR antigens and phenotypes in Dutch coeliac children and their families
Authors: Mearin M. L. , Bouquet J. , Mourad N. , Schoorel E. , Sinaasappel M. , Biemond I. , Schreuder G. M. Th. , PEÑA A. S. , Gelderen H. H. van , Rood J. J. van
Published: July 2010

In a study on the HLA‐DR antigens and phenotypes in a series of Dutch coeliac children and their first‐degree relatives, the B‐cell antigens of 36 unrelated coeliac children, 110 first‐degree relatives of 33 of them, and 201 controls were typed with the two‐colour fluorescence test. The most frequent antigen was HLA‐DR3 (69%), followed by DR7 (36%). The distribution of DR phenotypes showed that the most frequent was DR3/other DR (25%), followed by DR3/DR7 (17%), DR3/DR4 (14%), and DR3/DR3 (14%). However, due to the frequency of certain antigens in the controls, only phenotypes DR3/DR3 (relative risk = 6.2), DR3/DR7 (relative risk = 6.4), and DR3/DR4 (relative risk = 6.2) were significantly associated with CD. The family study confirmed the segregation of the disease with phenotypes DR3/DR3 and DR3/DR7. The present results show that the association between CD and phenotypes DR3/DR3 and DR3/DR7 is not an exclusive characteristic of Southern coeliac children.
Sister chromatid exchange with and without in vitro mutagen induction in cultured skin fibroblasts from patients with adenomatosis of the colon and rectum
Authors: Heim Sverre
Published: July 2010

Fibroblast cell strains were obtained from skin biopsies taken from patients with adenomatosis of the colon and rectum (ACR), and their relatives. A total of 50 different fibroblast strains were tested for their frequencies of sister chromatid exchange (SCE) in vitro. These strains included nine from patients with the Gardner syndrome, 21 from patients with non‐Gardner ACR, and 20 cell strains from healthy relatives who were not at an increased risk for ACR. In 23 strains, the SCE frequencies after in vitro exposure to N‐methyl‐N'‐nitro‐N‐nitroso‐guanidine (MNNG) were also determined. Both with and without MNNG induction, SCE values in the Gardner strains were found to be significantly higher than in the control strains (p<0.02 and p<0.03, respectively). Non‐Gardner ACR strains differed only slightly from controls, thus making the difference between the control group and the pooled Gardner + non‐Gardner ACR group not significant. In all groups, there was a significant increase in SCE after MNNG exposure, and those strains which had low SCE values spontaneously, also tended to have relatively moderate SCE values after MNNG induction. There was no significant difference between the ratios of SCE values with and without MNNG exposure in the different groups.
Survival in trisomy 18: Life tables for use in genetic counselling and clinical paediatrics
Authors: Carter P. E. , Pearn J. H. , Bell J. , Martin N. , Anderson N. G.
Published: July 2010

Clinical management of neonates with Trisomy 18 depends on a knowledge of life expectancy. True estimates of potential life span are required for genetic counselling purposes when parents interpret the genetic threat, not only in terms of the mathematical odds involved, but also in terms of the quality and length of life of an affected infant, should such be born. This paper reports the findings from a study to generate life tables for Trisomy 18. This study is a total population study over 10 years based on a primary population of 2.2 million. Forty‐eight cases of Trisomy 18 were identified, five at amniocentesis. Four of the 43 clinical cases (9%) were mosaics. The median life expectancy for live‐born infants was five days (range one hour to 18 months). Mean age at death was 48 days. Life tables, by sex and by sub‐types (associated congenital abnormalities) are presented. The annual incidence is 14 per 100,000 total births, with a prevalence estimate of 0.06 per 100,000 total population.
Diabetes mellitus in Huntington disease
Authors: Farrer Lindsay A.
Published: July 2010

There have been conflicting reports that individuals with Huntington disease (HD) are prone to abnormalities of carbohydrate metabolism. In this study information about the incidence and control of diabetes mellitus in 620 probands (278 living, 332 deceased) with HD and in their first and second degree relatives was obtained by questionnaire method from participants of the National HD Research Roster. Among the probands, 65 individuals (10.5%) were identified by the informant or verified by examination of Roster family records as diabetic. The prevalence of diabetes, particularly among those less than 50 years of age, is significantly greater than corresponding figures among the general U.S. Caucasian population (Scott 1977, Krolewski & Warram 1985). Incidence rates were not calculated because of ascertainment and other biases in the data. Results from the analysis of family data indicate that HD affected relatives of an HD proband with diabetes are 7 times as likely to have diabetes over the proband's non‐HD relatives. A non‐diabetic HD proband is equally likely to have an HD or non‐HD relative with diabetes.
A new nail dysplasia syndrome with onychonychia and absence and/or hypoplasia of distal phalanges
Authors: Cooks Roberta Goldshlag , Hertz Marjorie , Katznelson Marissa Bat Miriam , Goodman Richard M.
Published: July 2010

A family in which two generations have a rare and previously undescribed form of nail dysplasia with bone abnormalities is reported. This disorder is characterized by onychodystrophy, anonychia, brachydactyly of the fifth digit of the hands, and digitalization of the thumbs, with absence and/or hypoplasia of the distal phalanges of the hands and feet. The probable mode of transmission is autosomal dominant.
Non‐dermatological complications and genetic aspects of the Rothmund‐Thomson syndrome
Authors: Starr D. G. , McClure J. P. , Connor J. M.
Published: July 2010

We report two new cases of Rothmund‐Thomson syndrome which emphasise the less well‐known non‐dermatological complications, namely: hypodontia, soft tissue contractures, proportionate short stature, hypogonadism, anaemia and osteogenic sarcoma. Genetic analysis of these and previously reported pedigrees supports autosomal recessive inheritance.
Studies on human low serum IgD phenotype and Gm markers
Authors: Litwin S. D. , Tse‐Eng D. , Jr V. P. Butler , Pernis B.
Published: July 2010

The human “low serum IgD phenotype” was studied by simultaneous Gm typing and IgD immunoassay of several populations. An association between Gm (f+b +) haplotype and low human IgD was confirmed and extended to the “low serum IgD phenotype” ‐ as defined from population distribution and genetic studies by Dunnette et al. 1978. Further, it was shown that Black American sera determined by Gm haplotype, had a similar percentage of “low serum IgD phenotype” samples (16%) although they lacked the “associated” Gm(f+b +) haplotype of White American samples. Sardinian sera showed a low incidence of the “low serum IgD phenotype” which was not correlated with Gm haplotype distribution. Familial aggregation of the “low serum IgD phenotype” was observed. No association was found between “low serum IgD phenotype” and serum IgE values. Age related abiotrophy of IgD could not be attributed to selective survival of “low serum IgD phenotype” persons.
The dysequilibrium syndrome: a study of the etiology and pathogenesis
Authors: Rasmussen Finn , Gustavson Karl‐Henrik , Sara Vicki R. , Floderus Ylva
Published: July 2010

The optimality of prenatal and perinatal conditions, serum levels of radioreceptor‐assayable somatomedins and activity of catechol‐O‐methyltransferase in erythrocytes were examined in 13 dysequilibrium (DES) patients. No differences from normal controls were found. As a group, the DES patients were not more exposed to non‐optimal prenatal and perinatal events than healthy controls. No association between DES and somatomedin levels or between DES and catechol‐O‐methyltransferase activity was demonstrated.
Cloacal exstrophy and related abdominal wall defects in Manitoba: Incidence and demographic factors
Authors: Evans Jane A. , Darvill Kathleen D. , Trevenen Cynthia , Rockman‐Greenberg Cheryl
Published: July 2010

A retrospective descriptive study of omphalocele and exstrophic defects of the abdominal wall was carried out in Manitoba to determine the prevalence of these defects, changes in birth incidence with time and their etiologic heterogeneity. The incidence of isolated omphalocele was similar to that reported in other series but the overall incidence of other types of abdominal wall defects was high. Cloacal exstrophy, bladder exstrophy and amnion disruption defects contributed significantly to the number of cases ascertained and emphasized the heterogeneity of abdominal wall defects. There were fluctuations in birth incidence with time with cloacal exstrophy especially apparently being more common in 1980‐81. No specific demographic or environmental factors were documented in the cases seen in 1980‐81 which could explain the high incidence in these years. Cloacal exstrophy is, however, now appreciated to be much more common than first realized. Studies directed at elucidation of the causes of apparent changes in incidence of malformations such as omphalocele or exstrophic defects will have to take into account both the fluctuations in background incidence of these defects and the considerable diversity in their etiology.
4‐methylumbelliferyl α‐N‐acetylglucosaminidase activity for diagnosis of Sanfilippo B disease
Authors: Marsh Jane , Fensom A. H.
Published: July 2010

Conditions for assay of a‐JV‐acetylglucosaminidase activity in human cultured fibroblasts, cultured amniotic fluid cells, leucocytes, serum, plasma and chorionic villi were studied using the fluorogenic substrate 4‐methylumbelliferyl‐2‐acetamido‐2‐deoxy‐a‐D‐glucopyranoside. The substrate was found to have advantage both in terms of sensitivity and ease of use over previously‐used colorimetric substrates for assay of the enzyme in these tissues, and for diagnosis of Sanfilippo B disease and identification of carriers. It should have particular application in first trimester prenatal diagnosis using chorionic villus biopsies.
Computed tomographic findings in manifesting carriers of Duchenne muscular dystrophy
Authors: Visser Marianne de , Verbeeten Bernard
Published: July 2010

Clinical and computed tomographic (CT) findings in 3 manifesting carriers of Duchenne muscular dystrophy are reported.

CT proved to be an important adjunct to the clinical examination: in all our 3 cases a decrease in density was found in various non‐paretic muscles.
Chromosome analysis in 100 cases of first trimester trophoblast sampling
Authors: Heim Sverre , Kristoffersson Ulf , Mandahl Nils , Mineur Anita , Mitelman Felix , Edvall Helene , Gustavii Björn
Published: July 2010

The cytogenetic findings in 20 experimental and 80 diagnostic cases of first trimester trophoblast biopsy are presented. All samples were obtained between the 8th and 13th week of gestation with the direct vision, trans‐cervical technique. Except when fetal sexing because of X‐linked disease was the issue, long‐term culture with in situ preparation was the method routinely employed in processing the biopsies for cytogenetic analysis. In 78 of the 80 clinical cases and in all reported experimental cases we were successful in establishing a karyotype from the sampled tissue. Unbalanced karyotypes were found in two experimental and six clinical cases. Tetraploidy was found in one clinical case, but was not confirmed in subsequently sampled amniotic fluid cells. In another clinical case, we were unable to confirm in the aborted placenta the trisomy 18 found in the trophoblast biopsy. In the rest of the induced abortions in the clinical series, the karyotype arrived at prenatally has been confirmed, and the 27 babies so far born have been healthy and with phenotypic sex corresponding to the prenatal findings. Six women have miscarried after sampling; in one of these cases the fetus had the karyotype 47,XX,+ 13.
Manifestation of the lines of Blaschko in women heterozygous for X‐linked hypohidrotic ectodermal dysplasia
Authors: Happle R. , Frosch P. J.
Published: July 2010

For the detection of the carrier state of X‐linked hypohidrotic ectodermal dysplasia, sweat pore counts on fingertips or palms have been used in the past. The results obtained, however, were sometimes difficult to interpret. We here describe a more reliable method, using the entire back as a test area. We provide evidence that the distribution of sweat pores in carriers is not simply patchy. In four heterozygous women we were able to demonstrate a linear distribution of hypohidrotic areas. This pattern followed the lines of Blaschko, forming a typical V‐shape over the spine. Apparently, these lines reflect the dorsoventral outgrowth of two functionally different populations of cells during early embryogenesis.
Age of onset in siblings of persons with juvenile Huntinqton disease
Authors: Hayden M. R. , Soles J. A. , Ward D R. H.
Published: July 2010

The age of onset distribution of Huntington disease (HD) has been defined for siblings of patients who exhibit the disease before age 20. The mean age of onset for the siblings of juvenile onset cases is 26.8 years, which is significantly less than the mean age of onset (39.8) observed in siblings of non‐juvenile cases. We have shown that the curve for age of onset in the general affected population is significantly different from that of the juvenile sibships. Furthermore, the significant regression equation suggests that the ‘expected age of onset’ of a sibling can be predicted from a knowledge of the age of onset of the juvenile proband. This information can be used to predict a range of age of onset for those sibs of juvenile patients who are likelv to be asymtomatic heterozygotes with DNA polymorphism studies.
EEC syndrome without ectrodactyly? Report of 8 cases
Authors: Küster W. , Majewski F. , Meinecke P.
Published: July 2010

Eight cases are presented from two families with a variable manifestation of the EEC syndrome. In the first family only one of three affected persons suffers from limb defects. In the second family all five affected have a different pattern of symptoms and only two of them show limb defects. The described families as well as at least one literature report confirm that ectrodactyly is not an obligate symptom of the EEC syndrome.
Agenesis of the corpus callosum and macrocephaly in siblings
Authors: Young I. D. , Trounce J. Q. , Levene M. I. , Fitzsimmons J. S. , Moore J. R.
Published: July 2010

A brother and sister with developmental delay, relative macrocephaly and agenesis of the corpus callosum are described. The brother also had unilateral cerebellar hypoplasia and malrotation of the large bowel. Published cases of familial agenesis of the corpus callosum are reviewed and the value of ultrasonography in demonstrating agenesis of the corpus callosum in the neonate is emphasised.
X inactivation patterns in two syndromes with probable X‐linked dominant, male lethal inheritance
Authors: Wieacker Peter , Zimmer Jürgen , Ropers Hans‐Hilger
Published: July 2010

For Incontinentia pigmenti Bloch‐Sulzberger (IP) and Aicardi syndrome, an X‐linked dominant transmission with lethality in hemizygous males has been proposed. The typical transition from inflammation to verrucous hypertrophy and hyperpigmented skin areas in IP suggests a gradual replacement of defective cells by normal cells. This would imply a preferential inactivation of the X chromosome carrying the IP gene with a proliferative advantage of this cell population. We have confirmed this hypothesis by demonstrating that the same X chromosome is preferentially active in fibroblasts grown from normal and hyperpigmented skin of an affected girl. In contrast, X inactivation was random in a girl with Aicardi syndrome.
Trismus‐pseudocamptodactyly syndrome in a Japanese family
Authors: Tsukahara M. , Shinozaki F. , Kajii T.
Published: July 2010

A family in which five individuals through three generations were affected with trismus‐pseudocamptodactyly syndrome is reported. The propositus, an 8‐year‐old boy, had a right embedded ear, inability to open the mouth fully, pseudocamptodactyly and soft tissue syndactyly of the toes. His paternal grandmother, father, paternal uncle and his paternal cousin had pseudocamptodactyly. The occurrence of the syndrome in this Japanese family indicates that the syndrome is not exclusively of Dutch origin.
A Weaver‐like syndrome with endocrinological abnormalities in a boy and his mother
Authors: Stoll C. , Talon P. , Mengus L. , Roth M. P. , Dott B.
Published: July 2010

A boy and his mother had dysmorphic features and accelerated growth of prenatal onset suggestive of the Weaver syndrome. Both had endocrinologic abnormalities. The boy had very low, hGH, which did not respond to stimulation. The mother had low, non‐stimulate hGH hyperprolactinemia with secondary amenorrhea and galactorrhea. This is the first report of a mother to son transmission of the condition.
Linkage relationships of paraoxonase (PON) with other markers: indication of PON‐cystic fibrosis synteny
Authors: Eiberg H. , Mohr J. , Schmiegelow K. , Nielsen L. S. , Williamson R.
Published: July 2010

The linkage relationships of the serum arylesterase paraoxonase (PON) was examined in our Danish material of normal families and in Danish and English cystic fibrosis families. Highest lod scores were found between PON and cystic fibrosis. The combined lod score for this relationship was ẑ= 2.69 at θ=0.07 in males and θ=0.00 in females. When scored in accordance with a tentative three allele model for PON, the score was ẑ= 3.70 at the same theta values. Linkage studies for PON against 64 other polymorphic marker systems did not give any lod score above + 1.3 and PON still remains chromosomally unassigned. By the present screening about 2/3 of the genome could tentatively be excluded as the region of PON and cystic fibrosis.
Hirschsprung disease: a genetic study
Authors: Garver Kenneth L. , Law John C. , Garver Bettylee
Published: July 2010

This study examines the association of Hirschsprung disease with Down syndrome and calculates the recurrence risk for families of Hirschsprung patients. Information was collected from 134 histologically diagnosed patients with Hirschsprung disease, from Children's Hospital in Pittsburgh, PA between 1950 and 1977. One hundred and three patients had short segment Hirschsprung disease which is defined as involvement up to and including the sigmoid colon. Thirty‐one patients had the long segment type with aganglionosis extending in some cases to the small intestine.

As in other studies, we found a significant association between Hirschsprung disease and Down syndrome in that 5.9% of probands had both. Mean maternal age of cases with both Hirschsprung disease and Down syndrome (33.5 years) was significantly different from controls (26.7 years) and non‐Down syndrome Hirschsprung patients (26.6 years). The overall sex ratio for Hirschsprung disease was 3.6. Recurrence risks were dependent on proband sex and the degree of aganglionic involvement.
The Fryns syndrome: diaphragmatic defects, craniofacial dysmorphism, and distal digital hypoplasia Further evidence for autosomal recessive inheritance
Authors: Meinecke P. , Fryns J. P.
Published: July 2010

A further example of the Fryns syndrome is reported. The female infant presented a malformation syndrome with coarse facies including cleft lip and palate, distal limb hypoplasia, a diaphragmatic defect, and excessive body hair, most pronounced on the face. She died 5 days after birth. Consanguinity in the parents supports the hypothesis of autosomal recessive inheritance. Considering the severity of the internal malformations and the poor prognosis of this syndrome, prenatal ultrasound diagnosis in the 2nd trimester of pregnancies at risk should be attempted.
Guadalajara camptodactyly syndrome type II
Authors: Cantú J. M. , García‐Cruz D. , Gil‐Viera J. , Nazará Z. , Ramírez M. L. , Solé‐Pujol M. T. , Sánchez‐Corona J.
Published: July 2010

Two sisters and an unrelated girl presented a distinct intrauterine growth retardation‐malformation syndrome with short stature, microcephaly, pectus excavatum, hip dislocation, hypoplastic pubic region and genitalia, camptodactyly, talipes, shortened 2nd toes, hypoplastic patella and skeletal dysplasia probably due to homozygocity from an autosomal recessive gene.
The ocular form of osteogenesis imperfecta: a new autosomal recessive syndrome
Authors: Beighton P. , Winship I. , Behari D.
Published: July 2010

We have investigated a South African family of Indian stock in which 4 brothers and 2 cousins had a severe form of osteogenesis imperfecta (OI) together with blindness due to hyperplasia of the vitreous, corneal opacity and secondary glaucoma. To the best of our knowledge the syndromic association of OI and ocular problems of this type has not previously been reported, and we believe that this condition is a newly recognised entity. The pedigree is consistent with autosomal recessive inheritance.