bluuebunny/crossref_metadata_2025 huggingface dataset:
Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl
Authors: Clarke J. T. R. , Willard H. F. , Teshima I. , Chang P. L. , Skomorowski M. A.
Published: July 2010

A female child of healthy, unrelated parents presented at 12 months of age with a history of moderately severe developmental delay, macrocephaly, dysmorphic facies, hypotonia, hepato‐splenomegaly, mild generalized dysostosis multiplex, mucopolysacchariduria (dermatan and heparan sulfates), and Alder‐Reilly bodies in peripheral blood leukocytes. Iduronate sulfatase activity in plasma was markedly depressed: 0.11 units/ml/h (normal, 1.75 ±0.56, N = 6). Analyses of arylsulfatases A, B, and C, heparan N‐sulfatase, α‐mannosidase, β‐mannosidase, β‐glucuronidase, β‐hexosaminidase, β‐galactosidase, and α‐fucosidase activities in plasma, leukocytes, and/or cultured skin fibroblasts were all normal. Urinary sulfatide excretion was also within normal limits. Karyotypes of peripheral blood leukocytes and cultured skin fibroblasts were normal. Serum iduronate sulfatase activities in the parents were in the normal range (father, 1.63 units/ml/h; mother, 1.25 units/ml/h). The results of analyses of restriction fragment length polymorphisms (RFLP) of DNA from cultured skin fibroblasts with the use of probes for loci extending from Xpter to Xq28 showed X chromosome heterozygosity and confirmed the paternal origin of one of the X chromosomes. Studies on sulfur‐35 uptake in mixed fibroblast cultures showed cross‐correction of [35S]‐glycosaminoglycan accumulation between cells from the patient and normal cells or cells from a patient with Hurler disease; however, there was no cross‐correction between cells from the patient and those from boys affected with classical Hunter disease. This represents only the second confirmed case of Hunter disease reported in a karyotypically normal girl.
Robinow syndrome: report of two patients with cystic kidney disease
Authors: Wiens Lynn , Strickland D. K. , Sniffen Barbara , Warady Bradley A.
Published: July 2010

Two patients with Robinow syndrome and cystic kidney disease are described. We propose that this anomaly should be added to the spectrum of malformations associated with the syndrome.
Autosomal dominant familial spastic paraplegia: report of a large New England family
Authors: Cooley W. C. , Rawnsley E. , Melkonian G. , Moses C. , McCann D. , Virgin B. , Coughlan J. , Moeschler J. B.
Published: July 2010

A large New England family with autosomal dominant familial spastic paraplegia is described. In a pedigree of 173 individuals, 71 affected individuals are identified. Seventeen cases examined by the authors are described with regard to the natural history of FSP in this family. A staging system for following progress and planning interventions is proposed. Three illustrative cases are presented. In this family, FSP is found to have a homogeneous clinical course with nearly complete penetrance. Onset occurs at or before 3 years of age with involvement limited to the lower extremities. After the initial onset, no significant progression was noted. Early aggressive habilitative care may result in more functional ambulation.
Abnormalities of the cerebellum in oro‐facio‐digital syndrome II (Mohr syndrome)
Authors: Annerén G. , Gustavson K.‐H. , Jòzwiak S. , Kjartansson S. , Strömberg B.
Published: July 2010

Two patients with oro‐facio‐digital syndrome type II (OFD‐II, Mohr syndrome) with associated cerebellar atrophy are described. Three other cases of the Mohr syndrome with cerebellar abnormalities are cited from the literature. Cerebellar involvement seems to be a clinical feature of this syndrome. Unfortunately, there is a lack of CNS reports for many of the previously described patients. In all cases with this entity, careful neurological and radiological examinations of the cerebellum are recommended.
Heart‐hand syndrome II. A report of Tabatznik syndrome with new findings
Authors: Silengo Margherita C. , Biagioli M. , Guala A. , Lopez‐Bell Graciela , Lala R.
Published: July 2010

The association of upper limb malformations and congenital cardiac anomalies was established as a definite clinical and genetic entity by Holt & Oram in 1960. Significant variability of malformations in both the upper limbs and the cardiovascular system has been well documented. In 1978, Temtamy & McKusick reported a family studied by Tabatznik, in which upper limb deformities, including type D brachydactyly, occurred in association with cardiac arrhythmias as a dominant, either autosomal or X‐linked trait. They called this apparently new entity Heart‐Hand syndrome II to distinguish it from the Holt‐Oram syndrome. No other similar cases have subsequently been reported. We describe here the second family affected with the Tabatznik syndrome and add some new findings to the clinical spectrum of this condition.
Right‐sided microtia and conductive hearing loss with variable expressivity in three generations
Authors: Ørstavik Karen Helene , Medbø Sverre , Mair Iain W. S.
Published: July 2010

Familial cases of microtia and meatal atresia are rare, and both dominant and recessive inheritance have been suggested. We here report a family with right‐sided external ear malformations and conductive hearing loss in a grandfather, his daughter and granddaughter. The grandfather and the granddaughter both had microtia and meatal atresia, whereas the daughter had a normal outer ear except for a narrow meatus and auricular appendages. The pedigree suggests autosomal dominant inheritance with variable expressivity.
Partial trisomy 4p resulting from a balanced intrachromosomal insertion, 4(q313p14p16)
Authors: Hastings Rosalind , Hamer Beverley , Roth Simon , Lucas Mary
Published: July 2010

Partial trisomy 4p was found in a child with dysmorphic features. Cytogenetic investigations in the parents revealed an intrachromosomal insertion in the mother, 46,XX,ins (4)(q313p14p16). The proband was trisomic for 4p(p14p16) as a result of a recombination event in the mother's chromosome 4 at meiosis. The clinical features of the proband are compared with those found in the literature.
Congenital tracheal stenosis in Pfeiffer syndrome
Authors: Stone Pamela , Trevenen Cynthia L. , Mitchell Ian , Rudd Noreen
Published: July 2010

We report an infant with Pfeiffer syndrome (acrocephalosyndactyly type V) and a solid cartilaginous trachea lacking rings. This airway abnormality has been reported in a child with Crouzon syndrome but has not been described in Pfeiffer syndrome.
Phenotypic variability in Meckel–Gruber syndrome
Authors: Farag T. I. , Usha R. , Uma R. , Mady S. A. , Al‐Nagdy K. , El‐Badramany M. H.
Published: July 2010

Five Bedouin sibs are described with Meckel‐Gruber syndrome (MGS), an autosomal recessive disorder with multiple abnormalities. Each affected sib manifested only two of the three cardinal signs of MGS: occipital encephalocele and polycystic kidneys, lacking polydactyly. The phenotypic variability of the MGS pleiotropic gene is briefly discussed.
Activity of glucocerebrosidase in extracts of different cell types from type 1 Gaucher disease patients
Authors: Miranda M. Clara Sa , Aerts Johannes M. F. G. , Pinto Rui , Fontes Augusta , de Lacerda Lucia Wanzeller , van Weely Sonja , Barranger John , Tager Joseph M.
Published: July 2010

Glucocerebrosidase activity in extracts of leukocytes, Epstein‐Barr virus transformed lymphocytes and fibroblasts from Portuguese Type 1 Gaucher disease patients was studied. The residual glucocerebrosidase activity in all extracts from patients was less than 25% if measured in the presence of bile salt taurocholate. However, if measured in the absence of bile salt the residual enzyme activity in extracts from patients was cell type specific: it was severely reduced in the case of fibroblasts, mildly reduced in the case of lymphoblasts and not significantly reduced in the case of leukocytes. The glucocerebrosidase activity in extracts from all control cell types was stimulated by taurocholate. In the patients the enzyme activity in fibroblasts extracts was also stimulated but that in lymphoblasts and leukocytes was inhibited by the bile salt. The differences in glucocerebrosidase activity (in the absence of taurocholate) in extracts from different cell types from Gaucher disease patients are attributable to differences in the proportion of glucocerebrosidase present as a monomer with low activity (form I) and as a highly active aggregate (form II) that may also contain sphingolipid activator protein 2 (SAP‐2). In extracts from leukocytes and lymphocytes from Type 1 Gaucher disease patients, but not in those from fibroblasts, a relatively high proportion of enzyme is present in aggregated form with near normal specific activity.
Frontonasal dysplasia or craniofrontonasal dysplasia and the Poland anomaly?
Authors: Reardon William , Temple I. Karen , Jones Barry , Baraitser Michael
Published: July 2010

We describe a 10‐year‐old girl with features of a frontonasal dysplasia and a right‐sided Poland anomaly. As there has been one previous case report of pectoral muscle hypoplasia in association with craniofrontonasal dysplasia, the relationship between these two conditions is discussed.
Possible association of rare autosomal folate sensitive fragile sites and idiopathic mental retardation: a blind controlled population study
Authors: Chudley Albert E. , Ray Manoranjan , Evans Jane A. , Cheang Mary
Published: July 2010

The expression of folate sensitive fragile sites (FS) was assessed in cord blood lymphocyte cultures obtained from 790 newborns (NB) and in peripheral blood lymphocyte cultures from 326 institutionalized mentally retarded residents (MR). The mean rate of expression of common FS and the occurrence of rare FS was significantly higher in the MR population. Age, sex and history of chronic medication use did not appear to influence common FS expression in the MR population. 3/790 (0.38%) NB and 5/326 (1.53%) MR exhibited rare autosomal folate sensitive FS, a 4‐fold difference in incidence (P = 0.009, Poisson test). Four of the five MR who expressed rare FS were considered to have idiopathic MR (4/179 or 2.2%). The occurrence of rare FS in 1/147 (0.68%) MR with known etiology is not significantly different from the frequency of occurrence in the NB population (P = 0.428, Poisson test). In this population, rare FS appear to be overrepresented in the idiopathic etiology MR group.
Interstitial deletion of the short arm of chromosome 4 in a boy with mild psychomotor retardation and dysmorphism
Authors: Ishikawa Tatsuya , Sumi Satoshi , Fujimoto Shinji , Shima Yasuko , Wada Yoshiro
Published: July 2010

A 17‐month‐old boy is reported with 46,XY,del(4) (p15.2p15.32). He had mild psychomotor retardation and multiple minor anomalies, without growth retardation or microcephaly, which differs from the classical 4p‐ syndrome (Wolf‐Hirschhorn syndrome). The activity of dihydropteridine reductase, a genetic marker for chromosome 4p15.3, was half that in a normal control.
A new syndrome of aphalangy, hemivertebrae, and urogenital‐intestinal dysgenesis
Authors: Johnson Virginia P. , Munson David P.
Published: July 2010

Two cases of aphalangy, hemivertebrae, and urogenital‐intestinal dysgenesis in a sibship are described. This constellation of malformations may represent a previously undescribed autosomal recessive trait.
Cardio‐facio cutaneous syndrome: neurological manifestations
Authors: Gross‐Tsur Varda , Gross‐Kieselstein Eva , Amir Naomi
Published: July 2010

Cardio‐facio‐cutaneous (CFC) syndrome is a not uncommon syndrome with a characteristic face, mental retardation, abnormal skin and hair and congenital heart disease. We report the 16th case of this syndrome and give details of the spectrum of neurological manifestations in the cases so far reported.
Diabetes mellitus in a young man with Bloom's syndrome
Authors: Mori Seiji , Kondo Naomi , Motoyoshi Fumiaki , Yamaguchi Seiji , Kaneko Hideo , Orii Tadao
Published: July 2010

Bloom's syndrome (BS) is a rare autosomal recessive genetic disorder in which diabetes mellitus unusually frequently develops as a complication. We report on a 21‐year‐old Japanese male patient with BS who exhibited impaired glucose tolerance (IGT) in the initial oral glucose tolerance test (OGTT) and had developed patterns of diabetes mellitus by the second OGTT at the 2‐years‐and‐2‐months follow‐up. German and Passarge reported that the onset of diabetes in patients with BS was in late adolescence or early adulthood. Our results support the findings of German and Passarge. Therefore, when a person with BS reaches late adolescence or early adulthood, an OGTT is necessary to ascertain whether the patient has IGT or diabetes mellitus as a complication, regardless of whether or not diabetic signs such as glucosuria are present.
Partial lipodystrophy syndromes – a further male case
Authors: Reardon W. , Temple I. K. , Mackinnon H. , Leonard J. V. , Baraitser M.
Published: July 2010

Details are presented of a boy with partial lipodystrophy. Only one male case has previously been described with this condition. The spectrum of partial lipodystrophy syndromes and the inheritance thereof are discussed in relation to our case.
Homozygous C4A deficiency in systemic lupus erythematosus: analysis of patients from a defined population
Authors: Sturfelt G. , Truedsson L. , Johansen P. , Jonsson H. , Nived O. , Sjöholm A. G.
Published: July 2010

Homozygous C4A deficiency was found at a prevalence of 16% (13/80 patients) in systemic lupus erythematosus (SLE). The patients represented all diagnosed cases retrieved from a defined population in Southern Sweden, which minimizes the influence of patient selection. Photosensitivity was more common among C4A‐deficient patients than among other SLE patients (p<0.05). Otherwise, clinical features were similar in the two groups. In addition, no differences were found with regard to presence of various autoantibodies (anti‐dsDNA, anti‐Sm, anti‐RNP, anti‐SSA, anti‐SSB, rheumatoid factors and anti‐cardiolipin). In patients expressing both C4A and C4B isotypes, C4B/C4A quotients were fairly stable in plasma irrespective of disease activity. This argues against preferential break‐down of either isotype during complement activation in the disease. The increased photosensitivity of C4A‐deficient patients partly resembles the findings in patients with complete deficiencies of classical pathway components.
Attitudes of parents of cystic fibrosis children towards neonatal screening and antenatal diagnosis
Authors: Al‐Jader L. N. , Goodchild M. C. , Ryley H. C. , Harper P. S.
Published: July 2010

Information on parents' attitudes towards neonatal screening for cystic fibrosis (CF) and antenatal diagnosis by chorion villus biopsy (CVS) has been derived from a detailed questionnaire administered to parents of CF babies diagnosed early following newborn screening (18 babies), and later on account of clinical criteria (11 babies). Screening was by measurement of immunoreactive trypsin (IRT) on Guthrie card blood spots, which was the basis of the Wales/West Midlands IRT Screening Survey, 1985–1989. Families questioned were from Wales. Most parents supported screening: parents of 15/18 (83%) screened babies and 10/11 (91%) unscreened babies. Following antenatal diagnosis, 15/29 (52%) of families would abort a CF foetus. Neither standard of education nor social class correlated with attitudes to screening or antenatal diagnosis, although these factors were related to the parents' knowledge of CF in general. Several families emphasised the importance of minimal delay between the initial mention of the possibility of CF on IRT testing and confirmation (or otherwise) of the diagnosis. Four mothers acknowledged temporary rejection of their babies during the period of uncertainty or following the procedures of diagnosis, emphasising that neonatal screening for CF can have a psychological impact on the parent‐child bonding. Although most families supported neonatal screening for CF, this study underlines some of the difficulties which may be encountered during the procedure of screening for CF by IRT.
An isolated case of Duchenne muscular dystrophy (DMD) in a female with a deletion of DMD cDNA
Authors: Yoshioka Mieko , Yamamoto Yoshihiro , Furuyama Jun‐ichi
Published: July 2010

An isolated case of Duchenne muscular dystrophy (DMD) in a female who has a deletion of the DMD locus is described. This patient was a 26‐year‐old woman born to unrelated, healthy parents. She was initially examined at age 6 because of a waddling gait. At age 15, pseudohypertrophy of calves and pes equinus were observed along with proximal muscular weakness and wasting. Her serum creatine kinase level was high and histological evidence of muscular dystrophy was apparent on muscle biopsy. The patient was ambulant at age 15 and progression of motor disability has been slow. Chromosomal studies revealed a normal karyotype, and mental retardation is moderate. DNA analysis at age 26 revealed that she has a deletion of DMD cDNA 8 mapped within Xp21 and is heterozygous for the deletion. Since diagnosis of DMD is now dependent on the evidence of mutation or deletion at Xp21, this patient is thought to have a form of DMD. Expression of the DMD gene in the heterozygous state might be due to random but unequal lyonization.
Bes, Aesop and Morgante: reflections of achondroplasia
Authors: Hecht Frederick
Published: July 2010

The past perception of achondroplasia is reflected in art, beginning about 2000 B.C. Achondroplasia is thought to have provided a model for the representation of a series of figures including the Egyptian god Bes, the Greek teller of fables Aesop, and the Renaissance giant of fiction Morgante. Since these figures were basically viewed as good, the hypothesis is advanced that achondroplasia was perceived as a positive, not a negative, condition during at least part of the past four millenia.
Coronary artery disease and apolipoprotein A‐I/C‐III gene polymorphism: a study of Saudi Arabians
Authors: Johansen Klaus , Dunn Bruce , Tan Jenny C. Y. , Kwaasi Aaron A. A. , Skotnicki Antek , Skotnickl Mary
Published: July 2010

The infrequent band of 3.2‐kb of the apolipoprotein A‐I/C‐III polymorphic region has previously been found to be associated with coronary artery disease and with hypertriglyceridaemia in Caucasians. We studied the apolipoprotein A‐I/C‐III gene cluster polymorphism in 97 Saudi Arabians in relation to coronary artery disease. Patients were categorized as being with or without coronary artery disease on the basis of coronary angiography. Genomic blotting of Sac I‐digested chromosomal DNA with the use of an apolipoprotein A‐I gene probe revealed 4.2‐kb and 3.2‐kb hybridization bands. The genotype frequency of patients with and without coronary artery disease was not different. The frequency of the 3.2‐kb allele occurred in 16% of patients with coronary artery disease and in 21% of patients with normal coronary arteries (non‐significant). In conclusion, we have not been able to confirm in Saudi Arabians associations previously reported in Caucasians of the 3.2‐kb band and coronary artery disease.
A new transthyretin variant from a patient with familial amyloidotic polyneuropathy has asparagine substituted for histidine at position 90
Authors: Skare James C. , Milunsky Jeffrey M. , Milunsky Aubrey , Skare Ilze B. , Cohen Alan S. , Skinner Martha
Published: July 2010

A new transthyretin variant which lost an Sph I cleavage site within exon 3 has been characterized. A 260 bp sequence containing exon 3 was amplified using the polymerase chain reaction, and the variant was found to possess a Bsm I cleavage site not present in normal transthyretin. This led to the conclusion that the histidine at position 90 was replaced by asparagine, and amino acid analysis supported the conclusion. The discovery of this mutation suggests that intermolecular binding between hydrophobic polypeptide loops on the surface of transthyretin can lead to familial amyloidotic polyneuropathy.
Glyceryl ethers in peroxisomal disease
Authors: Poulos A. , Bankier A. , Beckman K. , Johnson D. , Robertson E. F. , Sharp P. , Sheffield L. , Singh H. , Usher S. , Wise G.
Published: July 2010

1‐O‐Alkyl and 1‐O‐alk‐1‐enyl (plasmalogens) glyceryl ether lipid levels were measured in postmortem brain and/or liver biopsies from 7 patients with ultrastructural and biochemical evidence of a defect in peroxisomal biogenesis and/or enzymological evidence of a disturbance in ether lipid synthesis. Near normal levels of both species of glyceryl ether lipids were found in neonatal adrenoleukodystrophy and infantile Refsum's disease but marked deficiencies were found in Zellweger's syndrome and rhizomelic chondrodysplasia punctata, the latter manifesting the most profound reduction in ether lipid levels. These observations suggest that little ether lipid biosynthesis occurs in vivo in rhizomelic chondrodysplasia punctata or Zellweger's syndrome. However, in some phenotypes with apparently gross reductions in peroxisomal numbers, e.g. neonatal adrenoleukodystrophy and infantile Refsom's disease, there is significant ether lipid synthesis in liver and brain.
Pigmentary dysplasias in long survivors with mosaic trisomy 18: report of two cases
Authors: Murano I. , Ohashi H. , Tsukahara M. , Tonoki H. , Okino F. , Atsumi M. , Kajii T.
Published: July 2010

We describe two patients, a 19‐year‐old girl and a 19‐year‐old boy, with mosaic trisomy 18 and pigmentary dysplasias. Both patients had profound growth and mental retardation, marked kyphoscoliosis, bushy eyebrows, bulbous nose, simple ears, and joint contractures ‐ clinical manifestations of long survivors with mosaic or non‐mosaic trisomy 18. In addition, the boy showed total asymmetry. Pigmentary dysplasias of the skin with hypopigmented whorls and streaks, initially absent or overlooked at the ages 2 and 15 years, were detected on close examination. It is advisable to check closely every long survivor with mosaic or purportedly non‐mosaic trisomy 18 for pigmentary dysplasias.
The cerebro‐reno‐digital syndromes: a new community
Authors: Lurie I. W. , Lazjuk G. I. , Korotkova I. A. , Cherstvoy E. D.
Published: July 2010

Two “new” syndromes of multiple congenital malformations with autosomal‐recessive inheritance are presented. One syndrome, found in 2 sibs of nonconsanguineous parents, included microcephaly, agenesis of the corpus callosum, pterygium colli, cystic renal dysplasia (CRD) and postaxial polydactyly (PP). The other, found in 2 female sibs of consanguineous parents, included micropolygyria, CRD, PP, and polysplenia. The literature review allows the delineation of a community of 19 “cerebro‐reno‐digital” syndromes with autosomal recessive inheritance, 14 of which include cerebral anomalies, CRD and PP. Three more autosomal recessively inherited syndromes had CRD (or renal fibrosis) and cerebral anomalies (without digital anomalies), three others involved cerebral and digital anomalies (without renal anomalies), and one further syndrome showed CRD and ectrodactyly (without cerebral defects). Such phenotypical similarity may be attributed to the fact that there are common links in the pathogenesis of the syndromes under study.
Rapp‐Hodgkin hypohidrotic ectodermal dysplasia syndrome
Authors: Walpole Ian R. , Goldblatt Jack
Published: July 2010

Four members in three generations of a family had Rapp‐Hodgkin hypohidrotic ectodermal dysplasia syndrome with variable involvement of teeth, hair, nails and palate, characteristic facies and mild heat tolerance problems. In addition, the proband had a high sweat sodium, hypogenitalism, hypothelia and marked cicatricial scalp atrophy and scarring. Inheritance of the condition was consistent with an autosomal dominant mode and the manifestations are described to delineate further this rare phenotype.
Beals syndrome: clinical and molecular investigations in a kindred of Indian descent
Authors: Viljoen D. , Ramesar R. , Behari D.
Published: July 2010

Eight members of a 3‐generation kindred of Indian descent with congenital contractural arachnodactyly (Beals syndrome) have been appraised. Considerable variation was noted in the clinical features of affected persons, and the previously unreported associated finding of clubbing of the fingers and toes was evident in two individuals. The family was investigated using conventional serum and protein markers, and RFLP probes for type I and II collagen. No linkage in affected members could be demonstrated with type I collagen probes.
Screening for fra(x) mutation and Klinefelter syndrome in mental institutions
Authors: Pecile Vanna , Filippi Giorgio
Published: July 2010

A total of 9153 male subjects in mental institutions from six different Italian districts were screened for the presence of bilateral microorchidism, in order to detect Klinefelter syndrome. Among the 212 microorchidic patients found, 33 had an XXY karyotype (15.5%). Ninety‐one Klinefelter patients with normal intelligence were also examined as a control group. Cytogenetical and clinical findings were compared in these two groups of patients and no difference was found. Two fra(x)positive subjects were found, one for each group of XXY patients; the influence of fra(x) mutation on their phenotype is discussed.
The direct early diagnosis of cystic fibrosis by the detection of the deltaF508 CFTR gene mutation in a prematurely delivered boy
Authors: Macek Milan , Macek Milan , Stuhrmann Manfred , Kulovany Eduard , Dolanská Marie , Koukolík František , Boehm Ingolf , Hronková Jana , Ježková Zdeňka , Paulová Magdalena , Martanová Hana , Zach Jiří , Reis André , Sperling Karl , Schmidtke Jörg
Published: July 2010

The suspicion of prenatal meconium ileus syndrome was raised in a pregnancy in a family with no history of cystic fibrosis because of significantly higher maternal serum alpha‐fetoprotein in the 16th and 19th week of gestation, dispersed areas with increased echogenity in the fetal abdomen, slight fetal ascites in the 24th–25th weeks of gestation, decreased amniotic fluid gamma‐glutamyltranspeptidase (GGT) activity and alpha‐fetoprotein level in the 25th–26th weeks, and normal 46,XY karotype of the fetus. The detection of a homozygous deltaF508 cystic fibrosis transmembrane regulator (CFTR) gene mutation, by means of PCR from a small amount of white blood cells and urine sediment cells, substantiated the diagnosis of cystic fibrosis in a prematurely delivered boy in the 28th week of gestation. The repeated sweat test was unsuccessful. The autopsy examination confirmed the diagnosis of cystic fibrosis. Fetal meconium ileus syndrome was complicated by peritonitis and by formation of a meconium pseudocyst. Direct PCR typing improves postnatal diagnostic possibilities in the early neonatal period in prematurely delivered babies when the sweat test is difficult to perform.
Monosomy of 1p13.3–22.3 in twins
Authors: Dockery Heather , Van der Westhuyzen J.
Published: July 2010

Twin girls with deletion 1p13.3→22.3 are reported. They are characterised by psychomotor retardation, short stature, narrowing of the external auditory meati and abnormalities of the digits. A high resolution analysis revealed the karyotype to be: 46,XX,‐1,‐4,‐9,‐18,+der(1)t(1:9) (p22.3;q13)inv(1)(p13.2:q25) del (1)(p13.3→22.3)t(4:18)(4qter→4q32.:18q22→18qter; 18qter→18q22::4q32→4qter). A phenotype‐karyotype correlation study of this case and three others did not support the delineation of a distinct syndrome.
Cutaneous lymphangioma and amegakaryocytic thrombocytopenia in Noonan syndrome
Authors: Evans D. G. R. , Lonsdale R. N. , Patton M. A.
Published: July 2010

A case of congenital cutaneous lymphangioma and amegakaryocytic thrombocytopenia in an infant with Noonan syndrome is described. These features broaden the phenotype of lymphatic and haematological abnormalities associated with this syndrome.
Holt‐Oram syndrome in four half‐siblings with unaffected parents: brief clinical report
Authors: Braulke I. , Herzog S. , Thies U. , Zoll B.
Published: July 2010

The Holt‐Oram syndrome was diagnosed in four offspring of three mothers and the same unaffected father. One additional child lacked the characteristic clinical features of the Holt‐Oram syndrome. In contrast to the general autosomal dominant inheritance with complete penetrance, our observation suggests a paternal mutation, resulting in mosaicism, probably restricted to the germline.
The value of deletion analysis for carrier detection in Duchenne muscular dystrophy (DMD)
Authors: Bejjani Bassem , Finn Paula , Milunsky Aubrey , Amos Jean
Published: July 2010

We performed genetic analysis for carrier detection for several at‐risk females in a four‐generation Duchenne muscular dystrophy (DMD) pedigree using deletion analysis. We demonstrated that dosage analysis is a suitable alternative method to determine the carrier status of female relatives of DMD patients shown to have a deletion within the DMD gene. Subsequently, we diagnosed an affected male fetus for an at‐risk female shown to be a DMD carrier by deletion analysis. The usefulness of deletion and linkage analysis are compared. In this family, linkage analysis was complicated by the unavailability of key family members, two recombination events and by previously undisclosed nonpaternity. We found that dosage analysis was more efficient than linkage for carrier evaluation in this family.
The ΔF508 mutation in mild adult forms of cystic fibrosis (CF)
Authors: Simon‐Bouy Brigitte , Mornet Etienne , Taillandier Agnes , Serre Jean‐Louis , Boue Joelle , Boue Andre
Published: July 2010

Twenty CF chromosomes from ten patients with mild adult form of cystic fibrosis were tested for ΔF508. This mutation was found to be significantly less frequent than in the severe form of the disease.
Cutis laxa: autosomal dominant inheritance in five generations
Authors: Damkier A. , Brandrup F. , Starklint H.
Published: July 2010

Cutis laxa is described in three cases: a 17‐year‐old man, his mother and his maternal grandmother. The onset of skin symptoms occurred from puberty to early adulthood. The skin was loose‐hanging, wrinkled and without elasticity. X‐ray examination showed numerous gastrointestinal diverticulae in the two older patients, and both had been operated on for abdominal hernia and genital prolapse. There were no cardiopulmonary symptoms. Histopathological investigation showed a reduction in the amount of elastic tissue in the dermis, but normally localized and ultrastructurally normal components. The family history revealed clinically similar cases in at least five generations, consistent with autosomal dominant inheritance.
Piebaldism: an autonomous autosomal dominant entity
Authors: Winship Ingrid , Young Karen , Martell Robert , Ramesar Rajkumar , Curtis Diana , Beighton Peter
Published: July 2010

Piebaldism is a disorder in which the major clinical features are patchy hypopigmentation of the skin and a white forelock. The manifestations of piebaldism overlap with those of other genodermatoses, in particular the Waardenburg syndrome, and it is uncertain whether piebaldism is a distinct entity. We have documented a family in which seven affected members in three generations have gross piebaldism without any additional stigmata. The intrafamilial phenotypic consistency is suggestive that this autosomal dominant disorder has independent syndromic status. Linkage studies using conventional gene markers failed to identity the locus of the faulty gene.
A 15‐item checklist for screening mentally retarded males for the fragile X syndrome
Authors: Butler Merlin G. , Mangrum Tim , Gupta Rishi , Singh Dharmdeo N.
Published: July 2010

A 15‐item checklist, including physical and behavioral features frequently observed in fragile X syndrome, was used in a prospective study of 188 mentally retarded males in order to identify males at risk for this syndrome. Of the 188 males, 19 were found to have the fragile X syndrome, while the remaining 169 males had no recognizable cause of their mental retardation, including normal chromosomes. Significant differences (p<0.01) were found between mentally retarded males with and without the fragile X syndrome with increased hyperactivity; shorter attention span; more tactile defensiveness, hand‐flapping, perseverative speech, and hyperextensibility; large ears and testes; higher frequency of simian creases or Sydney lines and plantar creases; and more positive family histories of mental retardation in the fragile X syndrome males. Multiple regression and discriminant analyses of the 188 males indicated several physical features were useful predictors for inclusion in the fragile X syndrome group. An overall correct classification rate of 93% was achieved based on 6 variables (plantar crease, simian crease, hyperflexibility, large testes, large ears, and a positive family history of mental retardation) that were entered into the discriminant equation. Therefore, our experience with a 15–item checklist suggests the potential of screening for the fragile X syndrome in mentally retarded males and that 6 of the 15 variables were particularly good predictors of this syndrome.
Acrodysostosis in two generations: an autosomal dominant syndrome
Authors: Hernández Rosa María , Miranda Antonio , Kofman‐Alfaro Susana
Published: July 2010

Acrodysostosis is a rare syndrome characterized by growth retardation, peripheral dysostosis and mental deficiency. X‐rays reveal generalized shortening of metacarpals, metatarsals and phalanges, hyperplasia of the first ray of the feet and premature skeletal maturation. Occasionally abnormal interpedicular spinal spaces, increased mandibular angle and hearing loss have been observed. We report a 19‐year‐old woman and her daughter examined at birth and subsequently at 6 years of age. The clinical and radiological characteristics are those of acrodysostosis. The syndrome is easily recognized at birth. The generalized corporal shortening is progressive and could be due to premature closing of epiphyses. The finding of an affected mother and her daughter support the postulate that acrodysostosis is inherited as an autosomal dominant syndrome.
Interstitial deletion of chromosome 2q associated with ovarian dysgenesis
Authors: Davis Everett , Grafe M. , Cunniff Christopher , Jones Kenneth Lyons , Bogart Mark
Published: July 2010

In the present report we describe a girl with mental retardation, Dandy‐Walker malformation, craniofacial anomalies, cardiac defect, and ovarian dysgenesis associated with an interstitial deletion of chromosome 2. The interstitial deletion in the proband was associated with an apparently balanced translocation involving chromosomes 2 and 7 in the father.
Personality in 47,XXY males during adolescence
Authors: Netley C.
Published: July 2010

The responses to the High School Personality Questionnaire and the Millon Adolescent Personality Inventory of a series of neonatally identified 47,XXY adolescent males and age‐matched controls were compared. The extra X males' results indicated that they were more assertive, impulsive and prone to conflict than controls. Individual differences in these characteristics among the extra X cases had little relationship to quality of parenting but were related to indices of pubertal development.
A clinical, cytogenetic and familial study of 307 mentally retarded, institutionalized, adult male patients with special interest for fra(X) negative X‐linked mental retardation
Authors: Haspeslagh M. , Fryns J. P. , Holvoet M. , Collen G. , Dierck G. , Baeke J. , van den Berghe H.
Published: July 2010

In this study we report the results of a systematic etiological, clinical genetic study in 307 institutionalized mentally retarded adult males. Special attention is paid to the nosology of X‐linked mental retardation. During the survey 63 males with one or more ‘Martin Bell’‐like features were identified in whom repetitive fragile Xq27–3 screenings were negative. In 13 of them, belonging to 9 different families, pedigree data were compatible with X‐linked inheritance. This finding confirms the existence of one (or more) forms of fra(x) negative mental retardation with ‘Martin Bell’‐like features.
Malformations in a child with dup (7 pter‐p15.1) and del (7 q36‐qter) as a result of familial pericentric inversion
Authors: Ramer Jeanette C. , Mowrey Philip N. , Ladda Roger L.
Published: July 2010

We describe a child with multiple anomalies and severe retardation with dup 7pter‐p15.1 and del 7q36‐qter as a result of a parental pericentric inversion of chromosome 7. The pericentric inversion was found in family members in 3 generations with 9 liveborn children who had severe anomalies probably associated with imbalances of chromosome 7.
Second case report of del(4) (q25q27) and review of the literature
Authors: Raczenbek Cynthia , Krassikoff Natalie , Cosper Paula
Published: July 2010

We report a malformed infant with a de novo interstitial deletion of 4q. This is the second patient reported with del(4) (q25q27). Although there are several common features such as marked hypotonia, cardiac abnormalities, cleft palate, and micrognathia noted in our case and that of Chudley et al. (1988), we conclude from our comparison of the seven previously reported cases involving deletions of bands 4(q25q27) that a specific phenotype cannot yet be described for this deletion.
Long‐term follow‐up in females with Ullrich‐Turner syndrome
Authors: Pelz Lothar , Köbschall Hellgard , Lübcke Ulla‐Grit , Krüger Gabriele , Hinkel Georg‐Klaus , Verron Günther
Published: July 2010

In accordance with Nielsen & Stradiot's protocol (1987), we report on the long‐term follow‐up in 50 adult females with Ullrich‐Turner syndrome. Attention is drawn mainly to social problems.
Germinal mosaicism in Crouzon syndrome. A family with three affected siblings of normal parents
Authors: Navarrete Carmen , Peña Ramón , Peñaloza Rosenda , Salamanca Fabio
Published: July 2010

Germinal mosaicism is reported in three siblings with Crouzon syndrome born to normal, unrelated parents. Other probable explanations for the features in this family are discussed.
A balanced complex chromosomal rearrangement (BCCR) with phenotypic effect
Authors: Porto G. Del , Grammatico P. , Sanctis S. De , Esposito M. , Rosa C. Di , Romano C.
Published: July 2010

The authors report on a case of balanced complex chromosomal rearrangement (BCCR) with phenotypic effect, describe the dysmorphisms and malformations observed, and discuss the various pathogenetic mechanisms. On the basis of these considerations, they underline the need for careful reporting of examined cases, distinguishing the characteristic signs from dysmorphisms that are described in several other chromosomal aberrations as well. Finally, they stress the importance of a more precise description of BCCRs for the purpose, among others, of a correct formulation of reproductive risk.
Association of a genetic polymorphism in human apolipoprotein B‐100 with intermediate density lipoprotein concentrations
Authors: Robinson Miguel T. , Butler René , Krauss Ronald M.
Published: July 2010

Immunochemical techniques have been used to identify five antigenic (Ag) sites on apolipoprotein B‐100 (apoB), the major protein constituent of very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL). Each Ag site results from allelic variation at a specific locus of the apoB gene. In the present study, we assessed whether variations in the five Ag loci were associated with concentrations of plasma lipids or lipoprotein fractions measured by analytical ultracentrifugation in a group of 44 healthy men. Pair‐wise analyses of the Ag markers revealed that Ag(al/d), in association with either Ag(x/y) or Ag(t/z), is significantly related to plasma IDL‐mass concentrations. In this cohort we detected no significant associations of the Ag alleles (singly or in combination) with plasma total cholesterol, triglycerides, LDL‐cholesterol, HDL‐cholesterol, or mass of total VLDL or LDL. These results suggest that genetic variations in the apoB molecule may predispose to variations in concentrations of IDL that could have consequences for atherosclerotic risk.
Identification of a marker chromosome as inv dup(15) by molecular analysis
Authors: Shibuya Yoshitaka , Tonoki Hidefumi , Kajii Naofumi , Niikawa Norio
Published: July 2010

The origin of an extra marker chromosome in a patient with mental retardation and intractable epilepsy was ascertained by DNA analysis. Gene dose and restriction fragment length polymorphism (RFLP) studies of D15S9 proved that the patient was tetrasomic for the gene and that the extra chromosome was of maternal origin. On the basis of the molecular findings, further detailed GTG‐banded chromosome analysis interpreted the marker chromosome as inv dup(15)(pter→q14::q14→pter). The clinical manifestations of the patient are consistent with those of the patients previously described.
Cell line segregation in a 45,X/46,XY mosaic child with asymmetric leg growth
Authors: Papenhausen Peter R. , Mueller O. Thomas , Bercu Barry , Salazar Jose , Tedesco Thomas A.
Published: July 2010

Clinical evaluation of a 13 1/2‐year‐old male revealed a 4.4‐cm leg length discrepancy and a small penis with a normal endocrine evaluation. Cytogenetic analysis of peripheral blood lymphocytes and skin fibroblasts derived from the back showed 45,X/46,XY mosaicism with similar percentages of 45,X cells, 36% and 30% respectively. However, two separate skin fibroblast cultures derived from the thigh and calf of the short (right) leg showed significant lack of Y‐bearing cells with 100% and 80% 45,X, respectively. In contrast, skin biopsies of the thigh and calf of the normal (left) leg both showed 100% 46,XY. Similar evidence for differences in the percentages of Y‐bearing cells in the left versus right leg fibroblast cultures was obtained using densitometric scanning of dot blots following DNA hybridization with a Y‐specific probe at the DYZ4 locus. Asymmetric limb growth in cases of X/XY lymphocyte mosaicism warrants further cytogenetic investigation to substantiate possible genotype‐phenotype correlations which may help uncover the fundamental growth deficiency in Turner syndrome.
Biochemical effect of liver transplantation in two Swedish patients with familial amyloidotic polyneuropathy (FAP‐met30)
Authors: Holmgren Gösta , Steen Lars , Ekstedt Jan , Groth Carl‐Gustav , Ericzon B.‐G. , Eriksson Siv , Andersen Oluf , Karlberg Ingvar , Nordén Gunnela , Nakazato Masamitsu , Hawkins Philip , Richardson Suzanne , Pepys Mark
Published: July 2010

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder characterized by progressive peripheral and autonomic neuropathy, associated with neural and systemic amyloid deposits. The amyloid fibrils contain a variant transthyretin (TTR) molecule (TTR met30), over 90% of which is produced in the liver. After liver transplantation in two patients with severe symptomatic FAP, only normal TTR was detectable in circulation. The two patients are being monitored at regular intervals, and, although in one patient there was no evidence of reduction in the quantity of amyloid present at 6 months, there had been no further progression of the neuropathy.
Influence of serum paraoxonase polymorphism on serum lipids and apolipoproteins
Authors: Saha N. , Roy A. C. , Teo S. H. , Tay J. S. H. , Ratnam S. S.
Published: July 2010

One hundred and sixty‐three healthy Chinese subjects of both sexes were studied for serum paraoxonase (PON) polymorphism, and levels of lipids and apolipoproteins in order to examine effects of PON alleles on these parameters. The level of serum triglyceride was significantly higher in high activity allele (PON*B) compared with that in low activity allele (PON*A) in both sexes (P<0.01). The subjects with PON A had significantly higher LDL cholesterol (P<0.05) and lower Apo A‐II and ApoB levels. The influence of serum paraoxonase on serum lipids was estimated further by Spearman's rank correlation. In the males, there was a significant negative correlation of serum paraoxonase activity with total (P<0.05) and LDL (P<0.01) cholesterol levels, and positive correlation with HDL cholesterol and Apo A‐II levels (P< 0.05). Serum paraoxonase activity had a high positive correlation with serum triglyceride levels in both sexes (P< 0.001). Serum ApoB level had a positive correlation with the enzyme activity only in females (P<0.01). The allelic effect of PON on these parameters was studied by multiple regression analysis. The high activity allele (PON*B) was associated with higher serum triglyceride level (P<0.001) and ApoB (P<0.001), while it had lowering influence on total cholesterol (P<0.05) and LDL cholesterol (P<0.005) in men. The average allelic effect of PON was found to be about 22% for serum triglycerides, 11% for LDL cholesterol, 14% for Apo A‐II and 19% for Apo B in the present study. This study suggests a possible significant role of serum paraoxonase alleles in the metabolism of serum lipids and apolipoproteins.
Heterogeneity for mutations in medium chain acyl‐CoA dehydrogenase deficiency in the UK population
Authors: Curtis Diana , Blakemore Alexandra I. F. , Engel Paul C. , Macgregor Donald , Besley Guy , Kolvraa Steen , Gregersen Niels
Published: July 2010

MCAD is the commonest inherited disorder of fatty acid oxidation. We have sought for and studied 21 affected children from 18 families within the UK. In 14 families the children are homozygous for the G985 mutation. In three families the children are compound heterozygotes for G985 and thus carry another and unknown mutation. In one family the child does not carry the G985 mutation on either allele. The carrier incidence of the G985 mutation is 1 in 68, which suggests that the natural history of MCAD deficiency deserves further study.
Linkage analysis for the diagnosis of autosomal dominant polycystic kidney disease, and for the determination of genetic heterogeneity in Italian families
Authors: Turco Alberto , Peissel Bernard , Gammaro Linda , Maschio Giuseppe , Pignatti Pier Franco
Published: July 2010

Sixty‐eight individuals from six Italian families in which autosomal dominant polycystic kidney disease (ADPKD) is segregating, were typed in DNA polymorphisms linked to the PKD1 locus on chromosome 16. A total of ten probes were used: 3′ HVR, HMJ1, EKMDA, GGG1, 26–6, VK5B, 218EP6, 24.1, CR1090, and 41.1. Zmax was 4.502 at theta = 0.082 between ADPKD and 3′ HVR, and 4.382, 1.947, and 1.576 between ADPKD and GGG1, 26.6, and 218EP6, respectively, at theta = 0.0. No clear evidence of genetic heterogeneity was found. Multipoint analyses were consistent with linkage to PKD1. Twenty‐nine diagnoses and 16 exclusions made by ultrasonography were confirmed by genotype determinations; in two clinically uncertain cases, DNA analysis predicted one individual as being affected and the other unaffected.
Usher syndrome: results of a screening program in Colombia
Authors: Tamayo Marta L. , Bernal Jaime E. , Tamayo Gustavo E. , Frias Jaime L. , Alvira Gustavo , Vergara Oscar , Rodriguez Vicente , Uribe Jose I. , Silva Juan C.
Published: July 2010

Otological, ophthalmological and genetic studies were performed in 46 patients with Usher syndrome, identified through a screening program in Colombia. Of them, 69.6% had Usher syndrome type I, 26.1% type II, and 4.3% type III. Thirty‐three patients showed profound deafness (71.7%), while 13 (28.3%) had moderate to severe hearing loss. The ophthalmologic manifestations showed marked variability. Although the majority of the patients had serious ocular impairment before age 20. 32.6% had good central visual acuity. The prevalence of Usher syndrome in Colombia, estimated at 3.2/100000, warrants the implementation of screening programs in schools for the deaf and for the blind. Our study confirms that Usher syndrome shows no geographic or racial variation and that the disorder has a wide variability of expression and genetic heterogeneity. The large size of the families we have detected may provide important opportunities for further genetic studies, particularly in terms of the assignment of the locus and gene mapping.