bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyknoachondrogenesis: An association of skeletal defects resembling achondrogenesis with generalized bone sclerosis. A new condition?
Authors: Camera Gianni , Giordano Francesco , Mastroiacovo Pierpaolo
Published: July 2010

A stillborn male with skeletal anomalies resembling achondrogenesis with remarkably sclerotic bones is reported. The term “Pyknoachondrogenesis” is suggested for this hitherto undescribed condition.
Tapeto‐retinal degeneration in four Norwegian counties I
Authors: Grøndahl Jan
Published: July 2010

An attempt was made to trace all cases of tapeto‐retinal degeneration in Norway. Four counties (fylker) were selected for personal examination of probands with a diagnosis of unspecified tapeto‐retinal degeneration, retinitis pigmentosa, or Usher syndrome.

The examinations led to the rejection of the diagnosis of tapeto‐retinal degeneration in three persons, and in another four persons a diagnosis of choroidal dystrophy was made. The specific type diagnosis was adjusted in 26 additional persons.

The results indicate that in Norway the diagnosis of retinitis pigmentosa may be made too frequently. Patients with Usher syndrome, choroideremia or cone‐rod dystrophy are most often given the diagnosis of retinitis pigmentosa. Retinitis pigmentosa of pericentral type is in general not specified, and the diagnosis of tapeto‐retinal degeneration without specified type diagnosis and retinitis pigmentosa are sometimes intermingled.
Iris (Lisch) nodules in neurofibromatosis
Authors: Zehavi C. , Romano A. , Goodman R. M.
Published: July 2010

A group of 30 patients ranging from 4 to 56 years of age with the peripheral form of neurofibromatosis were evaluated for the presence of iris (Lisch) nodules. These nodules were observed in 73% of our cases and their presence was directly related to the severity of the skin manifestations of the disease. It is concluded that Lisch nodules are pathognomonic for neurofibromatosis and thus, their presence should be looked for in all suspected cases.
Inheritance of atrioventricular conduction time in Tokelau Islanders
Authors: Griggs L. H. , Chapman C. J. , McHaffie D. J.
Published: July 2010

The inheritance of A‐V conduction time in Polynesians has been examined, using ECGs taken from the population of the Tokelau Islands. As has been demonstrated in other racial groups, A‐V conduction time was influenced by sex, age, and heart rate.

Complex segregation analysis provides evidence for a significant polygenic influence on A‐V conduction, but no evidence for a major gene. Familial correlations and commingling analysis are in agreement with this conclusion. The heritability of A‐V conduction time was 0.46.

The hypothesis of M0ller & Heiberg (1980a) that a major gene could be influencing A‐V conduction, is not supported by these data.
Genetic control over fragile X chromosome expression
Authors: Hecht Frederick , Fryns Jean Pierre , Vlietinck Robert F. , Berghe Herman Van Den
Published: July 2010

The cytogenetic expression of fragile sites is highly variable. Sites are seen in differing proportions of cells. To determine if part of this variability is genetic, the proportions of lymphocytes manifesting the fragile X were examined in a large cohort of males with the fragile X chromosome. The number of fragile X cells was solely determined by genetic factors: the heritability as determined from the correlation between brothers as well as between cousins was 99.6% and 94.4%, respectively, as compared with 0% in unrelated males with the fragile X. This is consistent with pure genetic determination without any environmental influence over the expression of the fragile X chromosome in males.
α1‐antitiypsin deficiency and the flaccid lung syndrome
Authors: Klasen E. C. , Biemond I. , Laros C. D.
Published: July 2010

A significantly higher number of PI ZZ and PI MZ individuals was found in a flaccid lung population as compared to internal and healthy controls. The relative risk for ZZ is 12.5 and for MZ 1.8.

We conclude that if a PI MZ individual does develop lung disease, the excess risk due to the deficiency is negligible compared to MM individuals and is highly influenced or modified by other factors, possibly including both environmental and genetic.
Proximal duplications of chromosome 15: clinical dilemmas
Authors: Hood O. J. , Rouse Bobbye M. , Lockhart L. H. , Bodensteiner J. B.
Published: July 2010

The apparently rare cytogenetic abnormality of partial trisomy 15 was diagnosed by the authors in a patient presenting with developmental retardation, macrocephaly with ventricular enlargement and prominent subarachnoid spaces, hypotonia, low‐set ears, hyperextensibJe wrists and hands, high arched palate, tapering fingers, right esotropia, and bilateral metatarsus adductus. Clinical findings in this case are similar to previously reported cases of proximal duplications of chromosome 15 and bear some similarity to the Prader‐Willi syndrome. However, our patient did not have the severe hypotonia, early failure to thrive, or genital abnormalities seen in classical Prader‐Willi syndrome. This case supports the theory that a variety of cytogenetic aberrations in proximal 15q can cause a “Prader‐Willi‐like” syndrome. Increased clinical suspicion is needed when patients are seen with hypotonia, retarded development and mild dysmorphism if the variety of phenotypes are to be delineated.
High resolution pattern of an inverted duplication (15)
Authors: HOO J. J.
Published: July 2010

The nature and the origin of a supernumerary marker chromosome in a mentally retarded boy were determined by various staining techniques on metaphase chromosomes and by GBG high resolution technique. The karyotype was found to be 47, XY, + inv dup(15) (pter → q13: q13‐+pter) and the supernumerary chromosome was of maternal origin.
Chorion in culture
Authors: Procter Susan E. , Watt Jessie L. , Gray Elizabeth S.
Published: July 2010

This study is based on the processing of 115 samples of pure chorion. The different types of colony morphology, together with cytogenetic analysis, indicate the predisposition of chorion cells to artefacts of culture. Chorion survives longer than other foetal tissues and can be cultured when those are dead or contaminated (e.g. in macerated foetuses and missed abortions) making it a suitable and popular tissue for cytogenetic purposes. However, our results indicate that it is slow in culture and prone to chromosome variation so that pseudomosaicism frequently arises and may lead to misdiagnosis. We therefore suggest that cytogenetic analysis of spontaneous abortion material is interpreted with caution in cases where chorion is the only tissue cultured, especially when mosaicism is found.
Cytogenetic heterogeneity of translocations associated with Duchenne muscular dystrophy
Authors: Boyd Y. , Buckle V. J.
Published: July 2010

Lymphoblastoid cell lines have been established from nine female patients with Duchenne muscular dystrophy who had previously been reported to have chromosome translocations with breakpoints in the Xp21 region. A detailed cytogenetic comparison of prometaphase chromosomes in these cell lines revealed that six of the translocations had X chromosome breakpoints in the sub‐band Xp212 and that one further breakpoint could be assigned to either Xp212 or Xp213. These findings confirm and extend previous observations and provide strong evidence for Xp212 as the site of the Duchenne and Becker loci. For the remaining two translocations the simplest explanation for the observed banding pattern is that the X chromosome breakpoint lies a few thousand kilobases away, in the sub‐band Xp211. Other explanations which assume breaks in Xp212 combined with complex local chromosome rearrangements are also presented. It is also possible that the altered banding pattern in these two cases is due to the influence of local sequences on the staining or uncoiling properties of the chromatin.
Evidence for preferential involvement of chromosome bands 6p21 and 13q14 in amniotic fluid cell balanced translocation pseudomosaicism
Authors: Benn Peter A. , Hsu Lillian Y. F.
Published: July 2010

Chromosome rearrangement is a relatively common finding in cultured amniotic fluid cells. When cytogenetic abnormalities are confined to one cell or cells from a single culture, they are generally assumed to have arisen in culture (pseudomosaicism). To determine whether or not there might be some specificity in chromosome break‐points in balanced translocation multiple cell pseudomosaicism, data has been pooled for 18 cases studied at PDL and 30 cases from the U.S. survey on mosaicism and pseudomosaicism (Hsu & Perlis 1984).

Out of a total of 97 break‐points, 87 were assigned to Giemsa‐staining light bands and 12 to Giemsa‐staining dark bands. An excess of break points (29%) were assigned to terminal bands. Two loci appeared to be preferentially involved in rearrangement: 1) six break‐points (4 PDL cases and 2 others) were assigned to band 6p21; the region to which the major histocompatibility complex (HLA) has been assigned; 2) Four break‐points (all PDL cases) were assigned to 13q14, the region associated with the retinoblastoma locus.

This preliminary evidence for specific break‐points needs confirmation and long‐term follow‐up information is needed to determine whether or not there is any clinical significance to these observations.
Long term survival of a patient with the cerebro‐hepato‐renal (Zellweger) syndrome
Authors: Bleeker‐Wagemakers E. M. , Oorthuys J. W. E. , Wanders R. J. A. , Schutgens R. B. H.
Published: July 2010

A 13‐year‐old girl with severe mental retardation, tapetoretinal degeneration, an extinguished electroretinogram and sensoneurinal hearing loss is described. In early life the diagnosis of Zellweger (cerebro‐hepato‐renal) syndrome was considered because of hypotonia, craniofacial dysmorphia, abnormal liver functions and pipecolic aciduria.

Biochemical studies in fibroblasts from the patient revealed a general peroxisomal dysfunction comparable to the findings in Zellweger Syndrome. As the clinical presentation of this patient is essentially different from that in classical Zellweger patients, who usually die early in life, we recommend the study of peroxisomal functions in all patients with severe mental retardation, tapetoretinal degeneration and sensoneurinal hearing loss.
The Borjeson‐Fbrssman‐Lehmann syndrome
Authors: Dereymaeker A. M. , Fryns J. P. , Hoefnagels M. , Heremans G. , Marien J. , Berghe H. van den
Published: July 2010

The propositus of this report presents a peculiar dysmorphic syndrome associated with severe mental retardation and epileptic attacks. Morphological stigmata include a round, fatty face with large, somewhat protruding tongue, large normally formed ears, relative microcephaly, abundant abdominal fat, dwarfism with hyperkyphosis and short neck.

Analogous phenotypic abnormalities were present in the mother and a maternal cousin. The clinical and familial findings in this apparently rare mental retardation syndrome with apparently X‐linked dominant or autosomal dominant inheritance with variable expression and penetrance are discussed.
The McCune‐Albright syndrome: a lethal gene surviving by mosaicism
Authors: Happle R.
Published: July 2010

In the McCune‐Albright syndrome, fibrous dysplasia of bones and various forms of endocrine dysfunction are associated with multiple pigmented skin lesions. Examination of a 4‐year‐old female patient and comparison with photographs published in the literature revealed that the cutaneous pigmentation is arranged in a systematized pattern following the lines of Blaschko. Apparently, this pattern visualizes the dorso‐ventral outgrowth of two different populations of cells during early embryogenesis. As all cases of the syndrome are sporadic, it is postulated that the disease is caused by an autosomal “dominant” lethal gene, leading to loss of the zygote in utero. Cells bearing the mutation can only survive when they are intermingled with normal cells. The mosaic may arise either from a gametic half chromatid mutation, or from an early somatic mutation. This concept offers an explanation for the scattered asymmetric distribution of bone lesions, and for the observation that the endocrinopathy may be either of central or peripheral origin, according to the random distribution of the mutant population of cells.
Heterogeneity of Morquio disease
Authors: Beck M. , Glössl J. , Grubisic A. , Spranger J.
Published: July 2010

Further clinical heterogeneity of Morquio disease, mucopolysaccharidosis IV (MPS IV), is delineated by the observation of a 30‐year‐old man with unusually mild clinical manifestations. He is 156 cm tall, has comparatively mild skeletal abnormalities and fine corneal deposits. Keratosulfaturia is absent. N‐Acetylgalactosamine‐6‐sulfate (GalNAc‐6‐S) sulfatase (E.C. 3.1.6. –) was markedly reduced in his fibroblasts. The residual enzyme activity exhibited a pH profile comparable to that of patients with the “classical” form of the disorder. From our observation and a review of the literature it is concluded that Morquio disease can be divided in several subgroups: besides the severe (“classical”) type A there exist an intermediate and a mild form that are also caused by a GalNAc‐6‐S sulfatase deficiency. A late‐onset variant of Morquio disease, which is due to a deficiency of β‐galactosidase, has been classified as type B. In addition, patients with mild manifestation of the disease and normal activities in fibroblasts of GalNAc‐6‐S sulfatase and β‐galactosidase have been observed (type C). The genetic nature of the broad clinical variability of Morquio disease is incompletely understood: it is partially caused by different enzyme defects. Other factors thought to influence the clinical expression include the pH profile of the residual enzyme activity and an additional neuraminidase defect.
Multiple congenital anomalies in a child born after prenatal diagnosis of trisomy 20mosaicism
Authors: Holzgreve Wolfgang , Golabi Mahin , Bradley Joel
Published: July 2010

The clinical significance of trisomy 20 mosaicism in amniotic fluid cultures has remained unclear so far. We report data on a child with multiple congenital anomalies born after a diagnosis of true trisomy 20 mosaicism in 65% of amniotic fluid cells.

The child had generalized dysmorphic features, including facial dysmorphy resembling those of a child with Williams syndrome. The boy also had hypotonia and language delay. Although most of the published cases do not mention any abnormalities in children born after prenatal diagnosis of trisomy 20 mosaicism, the distinct cranio‐facial features and the similarities to previous reports of partial or complete chromosome 20 mosaicism raises the possibility that a recognizable pattern of malformation might be associated with the prenatally diagnosable condition in some cases.
Mental retardation in a North Swedish isolate
Authors: Gustavson Karl‐Henrik , Wetterberg Lennart , Modrzewska Krystyna
Published: July 2010

Twenty‐six mentally retarded patients from a North Swedish geographically isolated population were studied. The mentally retarded patients were short with pycnic body type. Neurological and psychiatric stigmata of variating functions and degrees were recorded. Neurogenic hearing defects, impaired vision, pathological EEG, widened subarachnoidal space found in CT, were among these stigmata. In three patients a urinary substance, probably urocanyl‐glycine, was found. The erythrocyte uroporphyrinogen‐I‐synthetase activity was high in four patients. Chromosome analysis showed some abnormalities which, however, were not systematically present. In the near family 23 persons with schizophrenia were found. The relationship between the mental retardation and the schizophrenic psychosis in the present families has not been explained. Further studies are called for to elucidate the genetic and environmental factors responsible for the two conditions.
Petros Tsipouras4
Authors: Bamforth Stephen , Børresen Anne‐Lise , Harper Peter S. , Berg Kåre
Published: July 2010

Marfan Syndrome is a genetic disorder of the connective tissue. Individuals from one large family with this disorder were genotyped for COL1A2 gene associated RFLPs. Our results demonstrated that the COL1A2 gene, encoding the proa2(I) collagen chain, segregated independently of the phenotype and it is therefore excluded as the mutant locus in this family.
The problem of isolated cases of Huntington's disease in South Wales 1974–1984
Authors: Quarrell O. W. J. , Tyler A. , Cole G. , Harper P. S.
Published: July 2010

A firm diagnosis of Huntington's Disease (HD) is based upon both clinical observation and a positive family history. 192 cases of HD occurred in South Wales over a 10 year period fitting both criteria but an additional 37 patients did not have affected relatives despite detailed enquiries. Twenty‐two of these were still thought to have HD on clinical grounds whilst this diagnosis was thought less likely for 15. Definite post‐mortem outcomes are known for 7 patients and the clinical diagnosis confirmed on 6 occasions. Details regarding these two groups are presented together with an additional case in which HD was given on the death certificate but a post‐mortem revealed a diagnosis of Kufs' disease.
Coexistent pseudohypoparathyroidism and D brachydactyly in a family
Authors: Graudal Niels , Milman Nils , Nielsen Lillian Staub , Niebuhr Erik , Bonde Jan
Published: July 2010

The occurrence of pseudohypoparathyroidism/pseudopseudohypoparathyroidism (PH/PPH) and D brachydactyly (DB) in different persons in the same family is described for the first time. The theory that PH/PPH, E brachydactyly (EB), acrodysostosis (AD) and DB are variable expressions of the same trait or allelic traits is proposed. It is advised that newborn babies in such families are investigated carefully in order to exclude hypocalcemic PH. It is suggested that EB is subdivided into 4 groups (Ei‐E4) according to the degree of symptoms.

The proband of this family was a unique case. In addition to normocalcemic PH she also suffered from hemochromatosis, another rare hereditary disease and she had an abnormal chromosome 20, not earlier described. Both findings were supposed to be coincidental.
Asymmetric crying facies with microcephaly and mental retardation. An autosomal dominant syndrome with variable expressivity
Authors: Silengo M. Cirillo , Bell G. Lopez , Biagioli M. , Guala A. , Bianco R. , Strandoni P. , Sario P. N. De , Franceschini P.
Published: July 2010

An infant boy with asymmetric crying facies, microcephaly, developmental retardation and failure to thrive is reported. His two siblings died in the newborn period because of complex congenital heart defects. The mother and the maternal grandmother have asymmetric crying facies, microcephaly and normal intelligence. A maternal aunt has severe physical and mental retardation, facial asymmetry, microcephaly, and cleft palate. This family allows an expansion of the spectrum of malformations associated with asymmetric crying facies and suggests autosomal dominant inheritance with variable expressivity.
Use of a biotinylated DNA probe specific for the human Y chromosome for rapid antenatal sex determination
Authors: Boehm Thomas L. J. , Drahovsky Dusan
Published: July 2010

We have cloned a male‐specific 3.4 kb human DNA sequence which showed only little cross‐hybridisation to autosomal sequences. To further enhance the specificity of the probe, we subcloned an internal Taql‐fragment resulting in clone pH343T33. This clone was used to determine the presence of Y‐chromosomal sequences in DNA extracted from amniotic cells and from chorionic villi by Southern and dot hybridisation assays, respectively. Using this clone, we correctly predicted fetal sex in all of 148 cases analysed. To facilitate the use of this clone in clinical practice, we simplified the dot hybridisation procedure so that it can be performed in less than 48 h. The procedure with 32P‐labeled DNA probes requires less than 0.5 mL of amniotic fluid; when biotinylated DNA probes are used, 3–5 mL of amniotic fluid usually suffice. We have used this probe in genetic counseling of families at risk for X‐linked disorders.
Heterozygous manifestations of Langer mesomelic dysplasia
Authors: Goldblatt J. , Wallis C. , Vilioen D. , Beighton P.
Published: July 2010

The mesomelic dysplasias are a heterogeneous group of genetic disorders with predominant skeletal manifestations in the forearms and shanks. We have documented, over a thirteen‐year period, the clinical and radiographic course of the condition in a boy with the Langer type of mesomelic dysplasia.

It has been suggested that dyschondrosteosis or the Madelung deformity are the phenotypic manifestations of the gene which causes Langer mesomelic dysplasia in the homozygote. Several relatives on both sides of the family which we studied had malformations of their forearms, in keeping with this concept. However, these anomalies differed from those of dyschondrosteosis and the classical Madelung deformity; the exact syndromic status of the heterozygous phenotype remains unsettled.
A male infant with holoprosencephaly, associated with ring chromosome 21
Authors: Aronson D. C. , Jansweijer M. C. E. , Hoovers J. M. N. , Barth P. G.
Published: July 2010

An infant with holoprosencephaly and a karyotype 46,XY,r(21) is reported. No distinctive craniofacial features suggesting holoprosencephaly were present in this infant who presented with epilepsy, microcephaly and scoliosis with hemivertebra Th 10.

This is the first report which links deletion of chromosome 2lq to the holoprosencephaly phenotype.
A case report of a de novo tandem duplication (5p) (p14 → pter)
Authors: Chia N. L. , Bousfield L. R. , Johnson B. H.
Published: July 2010

The case described in this paper represents on the basis of cytogenetic evidence, the first reported example of a de novo tandem dup(5p)(p14→pter). Clinical changes were minimal, unlike previously described cases in which more complex structural chromosomal changes were involved and a phenotype was provisionally attributed to dup(5p) (p14 → pter). The duplicated segment of minimal effect identified in this case involved more than five eighths of 5p. It is proposed that there is a localised critical segment elsewhere on the short arm of chromosome 5 (p11–p13), which when duplicated is of greater significance in terms of clinical effects.
Osteopetrosis
Authors: Bollerslev Jens
Published: July 2010

By a systemic search of osteopetrosis in the county of Funen, Denmark, the prevalence was 5.5/100,000 inhabitants.

The study disclosed 33 patients of whom 32 had the mild, autosomal dominant form of osteopetrosis. Two obligate carriers, who had the genotype but were not phenotypically affected. were disclosed. There was a great variation in the clinical manifestations; 39% were asymptomatic. The age of first appearance of symptoms also varied widely (8–76 years), with a tendency to increasing symptoms with aging. The frequency of fractures was low.

Plasma inorganic phosphate was low in 7% of the patients, and plasma acid phosphatase was increased in 39%.
A distinct congenital motor and sensory neuropathy (neuronal type) with dysmorphic features in a father and two sons. A variant of Charcot‐Marie‐Tooth disease
Authors: Ruiz C. , Rivas F. , Ramírez‐Casillas G. , Vázquez‐Santana R. , Mendoza‐Chalita B. , Feria‐Velasco A. , Tapia‐Arizmendi G. , Cantú J. M.
Published: July 2010

A 37‐year‐old male had clinical and electrophysiological features of hereditary motor and sensory neuropathy (neuronal type) with onset in infancy, as well as histological picture of neurogenic myopathy. Two sons, aged 2 and 3 4/12 years, showed congenital contraction deformities of feet, delayed motor development, and electrophysiological features similar to those of the father. All three also presented laryngeal abnormalities, peculiar facies, short neck, narrow shoulders and protruding chest. The authors conclude that this aggregate of anomalies constitutes a “new” syndrome probably due to an autosomal dominant gene.
Public records and recognition of genetic disease in Scotland
Authors: Collyer Susan , Mey Rhona De
Published: July 2010

The use of Scottish public records to assist in the study of genetic disease is described. Four examples are given of situations in which such data can assist in the management of genetic disease. Some problems and limitations are discussed.
Ichthyosis ‐ Cheek ‐ Eyebrow (ICE) syndrome: a new autosomal dominant disorder
Authors: Sidransky E. , Feinstein A. , Goodman R. M.
Published: July 2010

A family presenting with ichthyosis vulgaris, prominent full cheeks, sparse lateral eyebrows and other craniofacial and musculoskeletal defects is described in detail. This constellation of physical findings represents a new syndrome, transmitted in an autosomal dominant fashion. For reasons of simplicity it has been termed the / (ichthyosis), C (cheek), E (eyebrow) syndrome.
Major genes of eye color and hair color linked to LU and SE
Authors: ElBERG H. , MOHR J.
Published: July 2010

Eye color and hair color were studied in a large Danish family material, tested earlier for a comprehensive set of genetic marker systems. We found strong evidence for linkage of “green eye color” or GEY to the Lutheran‐Secretor systems (combined lod score 9.19). This would appear to identify a major gene with influence towards “green eye color”. We also found evidence for linkage of GEY to “brown hair color” or BRHC (lod score 5.06), which would appear to identify a second major gene influence in the same region of chromosome 19. Concerning the obvious association in the general population between eye color and hair color which could imitate linkage if it were reflected within sibships, we did not recognize any such intrafamilial association; in the pooled informative sibships GEY and BRHC were independently distributed (as were LU‐SE and GEY).
Contribution to the 18q‐ syndrome. A patient with del (18) (q22.3qter)
Authors: Felding I. , Kristoffersson U. , Sjöström H. , Norén O.
Published: July 2010

A patient with the typical features of the 18q‐ syndrome, but with the deletion restricted to the most distal part, bands q22.3‐“qter is reported. The cytogenetic finding is supported by a decrease in activity of the enzyme peptidase A.
Albinism, or the NOACH syndrome
Authors: Dorp D. B. van
Published: July 2010

After a 4‐year multidisciplinary study of albinism our findings will be presented here. Over a hundred albinos were examined, together with their heterozygote family members. Given this substantial patient and subject sample we were provided with the opportunity to: evaluate the results of standard diagnostic procedures, for example pedigree analysis, ocular and clinical examination; determine the diagnostic value of biochemical, and ultrastructural tests; and develop a new and viable albino diagnostic protocol, particularly for electrophysiological examination.

In the conclusions the following subjects are in order:

Diagnosis: Our most important finding up till now is that normally pigmented people who do not look like albinos can in fact be albinos.

Differential diagnosis: It appears that patients with autosomal recessive albinism can be normally pigmented, and patients with X‐linked albinism can be severely hypopigmented. We therefore propose to abandon the terms oculo‐cutaneous albinism (OCA), and X‐linked ocular albinism (XOA), and use the terms autosomal recessive albinism, and X‐linked albinism instead.

X‐linked albinism Forsius‐Eriksson type (XOAF): We assume that XOAF does not represent a true form of albinism.

Classification: Our results indicate that the phenotypical albino classification, which was a base for Witkop et al. (1978) to also obtain a genetical classification, supported by the hairbulb test, has not proved to be useful for the classification of tyrosinase negative (TNOCA), tyrosinase positive oculocutaneous albinism (TPOCA), and autosomal recessive ocular albinism (AROA) as genetically distinct forms.

Prevalence: Our prevalence estimate for all forms of albinism is at least 1:15,000, about 10% of the albinos have X‐linked albinism.

Definition: We want to modify the albino definition as a hereditary and congenital inborn error of metabolism related to the pigment cell, and resulting in a systemic disorder that is characterized by anomalies of eyes, and hypopigmentation in most cases or absence of pigment in skin, hair, and eyes, and of which the neuro‐anatomical consequences are the most characteristic.
A phenotypic male with true hermaphroditism and a 46,XX/46,XY/ 47,XXY karyotype
Authors: Wit J. M. , Quartero A. O. , Bax N. M. A. , Huber J.
Published: July 2010

A phenotypic boy presenting with gynaecomastia showed a mixed karyotype of 46,XX/46,XY/ 47,XXY. The left gonad was normally descended into the scrotum, but proved to be an ovary without any testicular structures. After left gonadectomy, plasma androgen and estrogen levels showed that the right gonad only contained testicular tissue. Seven patients with this form of triple mosaicism have been described but the clinical features are strikingly different among the described cases.
Molecular heterogeneity of translocations associated with muscular dystrophy
Authors: Boyd Y. , Munro E. , Ray P. , Worton R. , Monaco T. , Kunkel L. , Craig I.
Published: July 2010

Individual translocation chromosomes from six girls suffering from Duchenne or Becker muscular dystrophy (DMD or BMD) have been isolated in human‐mouse somatic cell hybrids. DNA prepared from these hybrids was probed with sequences physically close to the locus; these include a junction fragment from the site of the X:21 translocation (pXJI) and subclones from the pERT 87 (DXS164) region which are absent in a minority of male DMD patients. Both sets of sequences mapped within the area defined by the translocation breakpoints, confirming their close proximity to the DMD and BMD loci. Furthermore, the X chromosome breakpoints of the translocations can be divided into three categories depending upon their position in relation to the sequences recognised by pXJ1 and pERT 87. The genomic target disrupted by the translocations examined here is a minimum of 176 kb.
A final word on the tricho‐rhino‐phalangeal syndromes
Authors: Bühler E. M. , Bühler U. K. , Beutler C. , Fessler R.
Published: July 2010

Chromosomal findings in the majority of cases of TRP II (or Langer‐Giedion) syndrome and in some cases of TRP I syndrome lead to the conclusion that the former is due to a deletion extending from 8q24.11 to 8q24.13 whereas the latter is caused by an even smaller deleted segment, namely 8q24.12.

A case of tricho‐rhino‐phaiangeal syndrome type I with a mosaic deletion of band 8q24.12 is described.
Is disordered folate metabolism the basis for the genetic predisposition to neural tube defects?
Authors: Yates J. R. W. , Ferguson‐Smith M. A. , Shenkin A. , Guzman‐Rodriguez R. , White M. , Clark B. J.
Published: July 2010

Vitamin levels were measured in twenty women under 35 years of age with a history of two or more neural tube defect pregnancies. Each index case was compared with a female control matched for age, obstetric history and social class. The mean concentration of red cell folate in the subjects was 178 ng/ml, significantly lower than the mean of 268 ng/ml for the control group (P=0.005). Red cell folate levels showed a linear relationship with the number of neural tube defect pregnancies, the levels being lowest in women who had had three or four affected offspring. There was no significant difference in serum folate; plasma or white cell vitamin C; plasma vitamin A; thiamine, riboflavine or pyridoxine status; serum vitamin B12; plasma vitamin E; total protein, albumin, transferrin, magnesium, copper or zinc. Diet was assessed by a questionnaire. The dietary intakes of total folate and other vitamins except vitamin A were lower in the subjects than the controls but none of the differences were statistically significant. Regression analysis showed a difference between subjects and controls in the relationship of red cell folate to dietary folate.

This study demonstrates an association between susceptibility to offspring with neural tube defects and depressed red cell folate levels which cannot be entirely attributed to a lower dietary intake of folate. It is postulated that one factor predisposing to the occurrence of neural tube defects may be an inherited disorder of folate metabolism.
Trichodysplasia‐xeroderma: an autosomal dominant condition
Authors: Pinheiro M. , Freire‐Maia N.
Published: July 2010

We describe six generations of a family with an autosomal dominant condition combining different degrees of trichodysplasia and xeroderma.
Three cases of partial trisomy 9q in one generation due to maternal reciprocal t(6;8;9) translocation
Authors: Ten S. K. , Chin Y. M. , Tan S. K. , Hassan K.
Published: July 2010

A family is described in which three siblings had congenital abnormalities consistent with partial trisomy 9q syndrome. Karyotyping indicated that the mother was a carrier of two separate balanced reciprocal translocations involving three chromosomes (46,XX,t (6;8;9)(6q27;8p23;9q32;9q13)) resulting from four breakpoints. The three siblings had inherited the der(8) from their mother and hence were partially trisomic for 9q32→9qter and partially monosomic for 8p23→9pter (46,XX,der(8),t(8;9)(p23;q32)mat). The clinical features of the three cases were comparable to those reported in the literature.
Trisomy 2q and monosomy 11q in the same individual: the importance of considering the deleted segment
Authors: Ardinger H. H. , Path S. R. , Rhead W. J.
Published: July 2010

A female infant with multiple dysmorphic features and developmental delay was found to have partial duplication of the long arm of chromosome 2 and partial deletion of the long arm of chromosome 11 derived from a paternal balanced translocation, 46,XY,t{2;ll)(q33:q25). Clinically, the infant had features of both 2q+ and llq– syndromes. The importance of considering both the duplicated and deleted segment in unbalanced products resulting from familial translocations is emphasized.
A peculiar subphenotype in the fra(X) syndrome: extreme obesity‐short stature‐stubby hands and feet‐diffuse hyperpigmentation. Further evidence of disturbed hypothalamic function in the fra(X) syndrome?
Authors: Fryns J. P. , Haspeslagh M. , Dereymaeker A. M. , Volcke Ph. , van den Berghe H.
Published: July 2010

In this report we describe two fra(X) adults and two prepubertal fra(X) brothers with a combination of distinct phenotypic findings: extreme obesity, short stature, stubby hands and feet and diffuse hyper‐pigmentation. These clinical abnormalities may be an additional indication of a specific hypothalamic disturbance in the fra(X) syndrome.
Postmortem Menkes diagnosis from carrier testing of female relatives
Authors: Tønnesen T. , Siengo M. , Gerdes A.‐M. , Hansen J. C. , Reske‐Nielsen E. , Francescmni P. , Horn N.
Published: July 2010

A boy who died at 6 months of age was noted to have sparse, stubby and light hair, pili torti were observed microscopically, and his skin was dry and redundant. As a suspicion of Menkes disease was first raised after his death, serum copper and ceruloplasmin in serum were not measured. Unfortunately, no fibroblasts were available ‐ only fixed and paraffin‐embedded samples of brain, spleen and liver. The copper contents of the brain and the liver were lower than in an age‐matched control. Fibroblast cultures from the mother, the maternal grandmother, and a maternal aunt of the index patient were analysed for 64Cu‐uptake. All these females showed the uptake values expected for Menkes carriers, thus supporting the clinical suspicion of Menkes disease in the index patient. From the above‐mentioned results it was highly likely that the index patient had suffered from Menkes disease. Adequate genetic counseling could thus be offered to the family, and in the next pregnancy a first trimester prenatal diagnosis was performed.
Deletion of the DXS165 locus in patients with classical Choroideremia
Authors: Cremers F.P.M. , Brunsmann F. , van de Pol T.J.R. , Pawlowitzki I.H. , Paulsen K. , Wieringa B. , Ropers H.H.
Published: July 2010

Using various probes from the Xq21 region which is known to carry the choroideremia (tapeto‐choroideal dystrophy, TCD) locus, we have screened the DNAs from eight unrelated male choroideremia patients for microdeletions. In two of these patients, but not in any of 45 males tested as controls, lack of hybridization signals with probe plbD5 suggested a deletion encompassing the DXS165 locus and (part of) the TCD gene. Absence of additional clinical features in these patients and the fact that two closely linked, and probably flanking, TCD markers (DXYS1 and DXS72) are not deleted may indicate that the physical distance between the DXS165 locus and the TCD gene is small.
Prader‐Willi syndrome in two siblings: one with normal karyotype, one with a terminal deletion of distal Xq
Authors: Ishikawa Tatsuya , Kanayama Manabu , Wada Yoshiro
Published: July 2010

Two sibs, a 13‐year‐old girl and an 11‐year‐old girl, with typical clinical features of the Prader‐Willi syndrome (PWS) are reported. High‐resolution chromosome analysis showed the normal karyotype in the eider sister, and 46,X,del(X)(pter→q26.1:) in the younger sister. But an interstitial deletion of 15q was not detected in either of the cases. PWS is most probably an etiologically heterogeneous syndrome consisting of two subgroups, with partial deletion and non‐deletion of chromosome 15, respectively.
Homozygous variegate porphyria A severe skin disease of Infancy
Authors: Mustajoki Pertti , Tenhunen Raimo , Niemi Kirsti Maria , Nordmann Yves , Kääriäinen Helena , Norio Reijo
Published: July 2010

A boy exhibited severe bullous skin disease a few days after birth, followed by increased fragility of the exposed skin in spring and summer. Examination at 2 1/2 years of age led to characteristic biochemical findings: increased excretion of fecal porphyrins (coproporphyrin 121 to 131 and protoporphyrin 467 to 576 nmol/g dry weight), and increased erythrocyte protoporphyrin concentration (3643 to 4840 nmol/I). Lymphocyte protoporphyrinogen oxidase activity was very low in the patient (0.4 nmol/mg protein/h) and half‐normal (2.7 and 2.3 nmol/mg protein/h) in the parents, suggesting that the patient had homozygous variegate porphyria. Severe skin symptoms and a high concentration of red cell protoporphyrin concentration in an infant should prompt suspicion of homozygous acute hepatic porphyria.
Progressive mental regression in siblings with Morquio disease Type B (mucopolysaccharidosis IV B)
Authors: Giuguani R. , Jackson M. , Skinner S. J. , Vimal C. M. , Fensom A. H. , Fahmy N. , Sjövall A. , Benson P. F.
Published: July 2010

A brother and sister with clinical and radiological features of Morquio disease, but with atypical mental regression, are described. Leucocyte and fibroblast β‐galactosidase activity was deficient in the siblings, while N‐acetylgalactosamine 6‐sulphate sulphatase and neuraminidase were normal. Study of the residual fibroblast β‐galactosidase activity towards 4‐methylumbelli‐feryl and p‐nitrophenyl β‐D‐galactosides indicated that the mutation resembles that in typical Morquio B disease (increased Km and similar pH maximum) rather than that in GM1‐gangliosidosis. The patients have therefore been classified as having Morquio B disease with atypical mental regression rather than GM1‐gangliosidosis variants with particularly severe bony abnormalities. The mutation was, however, distinct from that in Morquio B disease since residual activity towards the alternative artificial substrate 4‐methylumbelliferyl‐β‐D‐fucoside was increased. The patients represent further examples of the heterogeneity that can result from mutation at the β‐galactosidase locus.
X‐linked dysmorphic syndrome with mental retardation
Authors: Prieto F. , Badía L. , Mulas F. , Monfort A. , Mora F.
Published: July 2010

We present a dysmorphic syndrome in eight males of the same family (four brothers, three cousins and one uncle) that is characterised by: mental retardation, facial dysmorphia, abnormal growth of teeth, skin dimple at the lower back, clinodactyly, patella luxation, malformation of lower limbs, abnormalities of the fundus of the eye and subcortical cerebral atrophy. These physical defects do not correspond to any previously described syndrome, which suggests that it is a new syndrome. According to the model of heredity this syndrome could be due to a mutant gene situated in the X‐chromosome.
X‐linked muscular dystrophy with early contractures and cardiomyopathy (Emery‐Dreifuss type)
Authors: Emery Alan E. H.
Published: July 2010

The original Virginia family with X‐linked muscular dystrophy with early contractures and cardiomyopathy (Emery‐Dreifuss type) has been reinvestigated 25 years later. The findings confirm that a cardiomyopathy, presenting most often as atrioventricular block, is a significant feature of the disease, which is characterized by the triad of: 1) slowly progressive muscle wasting and weakness with a humero‐peroneal distribution in the early stages; 2) early contractures of the elbows, Achilles tendons, and post‐cervical muscles; and 3) a cardiomyopathy usually presenting as heart block (some female carriers may also develop heart block). Other reported families with X‐linked Emery‐Dreifuss muscular dystrophy as well as a rare autosomal variant are reviewed, and differentiation from scapulo‐peroneal muscular dystrophy and the rigid spine syndrome is discussed.
Family resemblance for fasting blood glucose: the Jerusalem Lipid Research Clinic
Authors: Friedlander Y. , Kark J. D. , Bar‐On H.
Published: July 2010

Familial aggregation of fasting plasma glucose was studied in a sample of families examined at the Jerusalem Lipid Research Clinic. We first examined homogeneity of familial correlations across major origin groups in the Israeli sample. Correlations were generally homogeneous across origin groups, except for mother‐son pairs. The pooled familial correlations were relatively low for unadjusted blood glucose values, and somewhat higher upon adjustment for sex, age, ethnicity, education, seasonality, body mass, cigarette smoking, alcohol consumption and dietary intake. Genetic and cultural determinants of blood glucose were estimated utilizing a path model with 10 parameters to be estimated from a total of 16 correlations. Under a reduced model genetic heritability (h2) was estimated to be 0.18±0.08 and cultural heritability (c2) was 0.10 4±0.02. However, within this population the additive variation could be explained by a cultural model of inheritance without introducing genetic parameters, and most of the variance is due to “random” unmeasured environmental factors. Commingling analysis was also performed, and our findings imply that there is no evidence for admixture in the distribution of fasting blood glucose in this Israeli population sample.
Isochromosome (18q) in siblings*
Authors: Krüger Gabriele , Götz Jürgen , Dunker Helmut , Pelz Lothar
Published: July 2010

A report is presented on a familial occurrence of isochromosome (18q) in a newborn infant and in a fetus in the 24th week of gestation after amniocentesis.
Effect of screening for cystic fibrosis on the influence of genetic counseling
Authors: Dankert‐Roelse Jeannette E. , te Meerman Gerard J. , Knol Klaas , ten Kate Leo P.
Published: July 2010

We studied the influence of genetic counseling for cystic fibrosis on family planning, using neonatal screening, family size at time of diagnosis, and maternal age as possible determinants for reproductive behaviour. The expected number of children born to mothers of equal age and parity in the same period was approximated on the basis of population statistics. These numbers were compared to the numbers of children born in the study group after a CF diagnosis and information on the 25% recurrence risk were given. A 50.8% reduction in childbirth was found in the study group, although 77% of families had decided against further high‐risk pregnancies. No statistically significant influence of neonatal screening could be demonstrated, but this may be due to the small number of families involved.
Genetic history: II. The Cohens of London
Authors: Hecht Frederick , Hecht Barbara K.
Published: July 2010

The genetic history in contemporary pedigree form is a useful tool for historical reading and study. The pedigree provides a guide to related personages and a data base for analysis. These points are illustrated by the family of Levi Barent Cohen, who came to London in the 18th century. There have been comparatively few consanguineous matings in the Cohen family. The family members have played central roles in Anglo‐Jewish life in their own right and through marriage to other families such as the Monteflores and Rothschilds.
PEDIGREE‐PLOT: a computer program for plotting pedigrees
Authors: Fenger Kirsten , Sørensen S. A.
Published: July 2010

PEDIGREE‐PLOT is a FORTRAN program which can be used for the drawing of pedigrees in either a horizontal or a circular shape. Eight different symbols are available for characterizing a person. Special symbols for stillbirth, abortion, unspecified sex, twins and half sibships exist.
Carrier detection of haemophilia A using DNA markers in families with an isolated affected male
Authors: Grover H. , Phillips M. A. , Lillicrap D. P. , Giles A. R. , Garvey M. B. , Teitel J. , Rivard G. , Blanchbtte V. , White B. N. , Holden J. J. A.
Published: July 2010

The carrier status of women in five families with an isolated haemophilia male was assessed by pedigree analysis, coagulation factor assays and DNA markers. In three families, ten women could be given very low risks of being carriers based on DNA analysis. In two of the families the DNA markers identified the mutation as originating in either the maternal or maternal grandfather's germ celt. Combined DNA and coagulation data suggested that the affected male in a third family was a de now mutation. DNA analysis of the affected male in another family identified a large deletion of the F8 gene which was present in his mother and three sisters, suggesting that the grandmother was a carrier. A combination of coagulation factor data and DNA marker assessment can determine the carrier status of the majority of females in families with isolated affected haemophilia A males.
Predicting intellectual functioning in 47,XXY boys from characteristics of sibs
Authors: Netley C.
Published: July 2010

Observations on the intellectual and educational functioning of neonatally identified 47, XXY boys and their sibs are presented. Equations for predicting the intellectual abilities of extra X boys on the basis of those of their sibs are provided. These may be useful to professionals engaged in counselling parents or possible parents of 47, XXY males.
Familial transmission of a ring chromosome 21
Authors: Hertz J. M.
Published: July 2010

A ring chromosome 21 was found in a phenotypically normal mother and her son. The clinical findings in the son were bilateral retention of the testes and a slightly delayed puberty onset. Consequences of a ring formation of a chromosome 21 in phenotypically normal patients are presented and discussed, and the previously reported cases of familially transmitted G‐group ring chromosomes are reviewed.
Tandem duplication (1) (q11 → q22) in a male infant with multiple congenital malformations
Authors: Mertens Fredrik , Johansson Berth. , Forslund Marianne , Olsson Marcel , Kristoffersson Ulf
Published: July 2010

An inverted tandem duplication of 1q11‐q22 was found in a male infant with severely retarded psychomotor development, growth retardation, and multiple congenital malformations. Tri‐somy for this segment of chromosome 1 has not been previously reported.