bluuebunny/crossref_metadata_2025 huggingface dataset:
Interstitial deletion of 22q11 in DiGeorge syndrome detected by high resolution and molecular analysis
Authors: Franke U. C. , Scambler P. J. , Löffler C. , Löns P. , Hanefeld F. , Zoll B. , Hansman I.
Published: July 2010

Two patients with DiGeorge syndrome (DGS), one with and one without characteristic dysmorphic facial features, were studied by high resolution banding, fluorescence in situ hybridization (FISH) and quantitative Southern blotting. In both patients, even in the one with no typical facial stigmata, a microdeletion within 22q11.2 was detected. FISH analysis, in particular, is most useful in screening for 22q11.2 segmental monosomy in patients with DGS and DGS‐related features.
Diphallus and associated anomalies with balanced autosomal chromosomal translocation
Authors: Karna Padmani , Kapur Saroj
Published: July 2010

We report a sporadic case of complete diphallus with multiple other anomalies in a premature newborn. Chromosomal analysis at the 500 band level showed an apparently balanced reciprocal translocation 46,XY, t(1;14)(p36.3;q24.3). The mother has a normal karyotype, but the father was not available for chromosomal analysis. The significance of this balanced chromosomal rearrangement and the possibility that the chromosomal breakpoints contribute to deregulation of mesodermal development is discussed.
Unilateral renal aplasia in X‐linked Kallmann's syndrome
Authors: Kirk J. M. W. , Grant D. B. , Besser G. M. , Shalet S. , Quinton R. , Smith C. S. , White M. , Edwards O. , Bouloux P.‐M. G.
Published: July 2010

Unilateral renal agenesis is an uncommon association with Kallmann's syndrome (KS) (hypogonadotrophic hypogonadism and olfactory defect). We have investigated affected individuals from six pedigrees: five with X‐linked KS, and one with X‐linked KS and X‐linked ichthyosis (XLI). Seventeen affected individuals have had renal imaging performed, and six scans demonstrated only one kidney. In addition, two pedigrees had males who died in the neonatal period with bilateral renal agenesis. Only two of the four affected individuals in the family with X‐linked KS and X‐linked ichthyosis (Pedigree 6) showed unilateral renal agenesis, despite all four patients demonstrating an interstitial deletion within the short arm of the X‐chromosome. These data indicate that unilateral renal agenesis is much commoner than previously suspected in patients with X‐linked Kallmann's syndrome, but that it may have incomplete penetrance within a family.
Determination of haemophilia A carrier status from hair samples using polymerase chain reaction technique
Authors: Hussain S. , Shamim A. , Vencer L. , Butt A. I. , Al‐Harithy R. , Nasim A.
Published: July 2010

The usefulness of intragenic restriction fragment length polymorphisms (RFLPs) for Bc1I, HindIII and XbaI, adapted for polymerase chain reaction (PCR), was tested for the detection of haemophilia A carrier status in the consultand of a family in which only haematological information was available on the inheritance of the trait. Hair follicles were used as the non‐invasive source of DNA. The mother was found to be homozygous for Bc1I and heterozygous for HindIII sites, whereas her status as regards informativeness could not be established for XbaI. On the basis of HindIII RFLP, the daughter was found to be a carrier of the haemophilia trait. This was confirmed by sequencing the amplified intron 19 of the mother and the daughter. The RFLP for XbaI did not appear to be suitable for carrier detection using PCR due to the difficulty of establishing homozygosity or heterozygosity from the results of digestion of the amplified product.
Congenital cardiac defect in a patient with mosaic 45,X/46,XX,i(21q) karyotype
Authors: Digilio M. C. , Mingarelli R. , Marino B. , Giannotti A. , Melchionda S. , Dallapiccola B.
Published: July 2010

A baby is described with 45,X/46,XX,i(21q) mosaicism. DNA analysis indicated that the abnormality arose from two independent postzygotic mutations in a 46,XX zygote, involving the paternal chromosomes 21 and X. In agreement with previous reports, most of the clinical dysmorphisms observed were consistent with Down syndrome. Moreover, congenital heart disease consisted of an atrioventricular canal associated with slight hypoplasia of the left ventricle and a mitral anulus, a complex defect including features found in both Down and Turner syndromes.
A cytogenetic register of trisomies in Scotland: results of the first 2 years (1989, 1990)
Authors: Carothers Andrew D.
Published: July 2010

A population‐based register of all autosomal trisomies diagnosed in Scotland was established in 1989. Data were provided by all cytogenetic service laboratories, and included karyotype, date and place of outcome, indication for analysis, maternal age and place of residence. The Register includes all foetuses diagnosed prenatally and all cytogenetically‐confirmed live‐ and still‐births with autosomal trisomy, including partial, mosaic and familial cases. In the 2 years 1989‐90, 76 prenatal and 147 postnatal diagnoses were notified. For Down syndrome karyotypes the estimated rate, assuming no terminations and after adjusting for spontaneous foetal losses following diagnosis, was 1.23 per 1000 livebirths. This was almost identical to that expected by applying published maternal age‐specific rates to the maternal age distribution in Scotland, indicating a very high level of ascertainment. The adjusted rates for trisomies 13 and 18 were also close to expected values derived from published data. Prenatal screening was estimated to reduce the newborn incidence of trisomy 21 by about one quarter overall, and about one half in mothers over 35 years. For trisomy 18, the estimated overall reduction was also about one quarter. It is concluded that the Register provides a practical and cost‐effective means of monitoring the effects of prenatal screening, with near‐complete ascertainment. In the longer term it will provide a database for studies of the actiology of these conditions.
Risk estimates for developing motor neurone disease in first‐degree relatives
Authors: James C. M. , Newcombe R. G. , Harper P. S. , Wiles C. M.
Published: July 2010

Patients with motor neurone disease resident in the three counties of South Glamorgan, Mid Glamorgan and Gwent (total population 1 394 400) from 1/11/91 to 31/12/92, were ascertained through general practitioners and neurology department records: 62 out of 71 (51 male, 20 female) index cases ascertained agreed to be visited. These individuals were clinically reviewed, had a detailed family history taken and, after discussion, had a blood sample taken for testing for the X‐linked bulbo‐spinal muscular atrophy mutation. The period prevalence of motor neurone disease was 5.02/100 000 with a mean age of onset of 59.4 (S.D. 12.9) years. One 66‐year‐old male was found to have the X‐linked bulbospinal muscular atrophy mutation. A single, definite first‐degree relative pair was identified, of whom only one was included in the data. The index cases had a total of 131 offspring and 173 siblings. The risk estimates, by current age, for these first‐degree relatives of patients with apparently sporadic motor neurone disease decreased from 1 in 85 at age 20 years to 1 in 1683 at age 80 years. These estimates require confirmation in an independent sample, as they are based on a single “event”.
Maternal 3;13 chromosome insertion, with severe pre‐eclampsia
Authors: Boyd P. A. , Maher E. J. , Lindenbaum R. H. , Hoogwerf A. M. , Redman C. , Crocker M.
Published: July 2010

A previously healthy young primigravida suffered very severe pre‐eclampsia and was delivered at 32 weeks gestation. The baby was growth retarded with dysmorphic features, and died aged 4 days. Chromosome analysis of the baby revealed partial trisomy 13 resulting from recombination within a maternal insertion of part of 13q into 3p. To date, the maternal insertion has been identified in a further three members of the family and may have contributed to a number of spontaneous abortions, stillbirths and neonatal deaths in other family members. The various possibilities for recombination and malsegregation are discussed. An association between pre‐eclampsia and trisomy 13 has been reported previously. To our knowledge this present paper constitutes the first report of partial trisomy for 13q occurring with pre‐eclampsia.
Increased frequency of the rare PstI allele (P2) in a population of CAD patients in Northern Greece
Authors: Vavatsi Norma A. , Kouidou Sophia A. , Geleris Paraschos N. , Tachmatzidis Christos , Gikas Theodoros , Tsifodimos Demetrios K. , Trakatellis Antonios C.
Published: July 2010

Restriction fragment length polymorphisms (RFLPs) at the apolipoprotein AI‐CIII‐AIV gene cluster and their association with coronary artery disease (CAD) and lipid levels were studied in a Northern Greek population. Ninety‐five patients with CAD and fifty‐four normal controls, angio‐graphically proven, were included in this study. Using genomic hybridization techniques, three polymorphic restriction sites were identified at this locus: the PstI at the 3′ end of the apoAI gene, the SacI at the 3′ non‐coding region of the apoCIII gene and the PvuII at the intergenic region between the apoCIII‐AIV genes. The rare allele (P2) arising from the absence of the PstI restriction site was observed with a significantly higher frequency (p<0.01) in patients compared to normals (0.11 vs 0.02). In contrast, the rare allele for the SacI polymorphic site had a similar distribution among patients and controls (0.12 vs 0.16). The same was observed for the PvuII RFLP (0.04 vs 0.05). Correlation of lipid and apolipoprotein AI levels with the three RFLPs revealed no significant association, although apo AI and HDL were lower in patients with the P2 allele. Thus, in this Greek population, only the PstI polymorphism, among the polymorphic restriction sites examined, appears to be associated with CAD.
Dicentric chromosome Y associated with Leydig cell agenesis and sex reversal
Authors: Genuardi Maurizio , Bardoni Barbara , Floridia Giovanna , Chiurazzi Pietro , Scarano Gioacchino , Zollino Marcella , Garcea Nicola , Martini‐Neri Maria Enrica , Neri Giovanni
Published: July 2010

The nature of a non‐mosaic marker Y chromosome observed in a pseudohermaphrodite patient with Leydig cell agenesis was investigated by high‐resolution chromosome analysis and molecular probes from the Y chromosome. Cytogenetically, the marker chromosome appeared to be an isodicentric, with breakage in Yq11.21. Double copies of all Yp‐specific loci tested, including SRY, were present. The most distal Yq portion detected in patient DNA was DXS278‐C, which maps to interval D in the chromosome Yq deletion map. Fragment DXS278‐B, which maps to deletion interval E, was absent. The possible relationship between this cytogenetic abnormality and Leydig cell agenesis, a finding never reported in association with Y chromosome rearrangements, is discussed.
Antley‐Bixler syndrome and esophageal atresia in a patient with trisomy 21
Authors: Feigin E. , Udassin R. , Seror D. , Szold A. , Neriah Z. Ben , Glick B.
Published: July 2010

The Antley‐Bixler syndrome (ABS) is characterized by craniofacial, skeletal and urogenital anomalies. While most patients with ABS die of severe respiratory complications in their first months, long‐term survivors have been reported. We report an infant girl, born to a consanguineous couple, with craniofacial and skeletal anomalies, consistent with ABS, in addition to atresia of the esophagus and trisomy 21.
Impact of a common mutation of the LDL receptor gene, in French‐Canadian patients with familial hypercholesterolemia, on means, variances and correlations among traits of lipid metabolism
Authors: Roy Madeleine , Sing Charles F. , Betard C. , Davignon Jean
Published: July 2010

Structural and functional studies of the gene coding for the low density lipoprotein receptor in patients with familial hypercholesterolemia have uncovered over 180 mutant alleles of the gene. Although the classical familial hypercholesterolemia phenotype is well known, the range of phenotypic variability in lipid traits associated with particular mutations in familial hypercholesterolemia has not been extensively documented. We investigated the phenotypic distributions of plasma markers of lipid metabolism from a large sample of unrelated individuals who are heterozygous for a single mutation, a > 10 kb deletion in the low density lipoprotein receptor gene, and compared these distributions with those from a sample of healthy controls. Patients were pair‐matched for sex and age with healthy individuals selected from a previously studied French‐Canadian population from the same region. We examined the level and variation of seven lipid traits, the correlations between the traits, and the amount of overlap of the sample distributions for each trait. The low density lipoprotein receptor defect was found to affect the levels and variability of traits, and correlations between traits. There was some overlap of the distributions of lipid traits including that for low density lipoprotein cholesterol, which is a cardinal feature of familial hypercholesterolemia. The low density lipoprotein receptor gene has a sex‐specific pleiotropic effect and should be considered as a variability gene as well as a level gene. The extensive dynamic changes observed in the relationships between lipid traits testify to the biological complexity of genome type‐environment interactions.
Retinitis pigmentosa in India: a genetic and segregation analysis
Authors: Kar Bibhas , John Sheila , Kumaramanickavel G.
Published: July 2010

Seventy‐eight families with retinitis pigmentosa, presenting at the genetic clinic of Sankara Nethralaya, Madras, over a period of 6 months, (from April to September 1993), were assessed to determine the different genetic types: 9% were autosomal dominant; 36%, autosomal recessive; 3%, X‐linked recessive; 44%, isolated cases and 8%, undetermined genetic type. A high incidence of consanguinity was observed in autosomal recessive (57%) and isolated cases (37%). Segregation analysis showed good agreement in autosomal dominant (χ2=0.864) and recessive families (p=0.222). The high proportion of autosomal recessive and isolated cases in this study, when compared with other similar studies, is due to the high incidence of consanguineous marriages in the Indian subcontinent.
Pelizaeus‐Merzbacher disease: a point mutation in exon 6 of the proteolipid protein (PLP) gene
Authors: Pratt Victoria M. , Dlouhy Stephen R. , Hodes M. E.
Published: July 2010

Pelizaeus‐Merzbacher disease has been known since 1885. It is characterized by severe dysmyelination of the central nervous system. We describe a new mutation in exon 6 of the proteolipid protein gene in a 9‐year‐old boy with severe connatal Pelizaeus‐Merzbacher disease.
Correlation between magnitude of CAG repeat length alterations and length of the paternal repeat in paternally inherited Huntington's disease
Authors: Nørremølle Anne , Sørensen Sven Asger , Fenger Kirsten , Hasholt Lis
Published: July 2010

An increasing number of diseases are being found to be due to elongation of specific trinucleotide repeat sequences. Inverse correlation between the age at onset and the length of the repeat has been found in most of these. The elongated CAG repeat causing Huntington's disease is highly unstable when inherited from an affected father. In this study we found an average parent‐to‐offspring difference of +0.08 repeat units in maternally inherited repeats, significantly less than the average difference of +2.92 repeat units with paternal transmission. Large repeat expansions, of more than 5 repeat units, were seen only in paternally inherited cases. With paternal transmission the magnitude of repeat length alterations was directly correlated to increasing paternal repeat length. Increasing variation in repeat length among siblings was correlated to increasing average repeat length in the sibship in both maternally and paternally inherited HD. Comparison of the magnitude of repeat length alterations to parental age at the time of birth of the offspring showed no correlation.
Exclusion mapping of the benign hereditary chorea gene from the Huntington's disease locus: report of a family
Authors: Yapijakis C. , Kapaki E. , Zournas C. , Rentzos M. , Loukopoulos D. , Papageorgiou C.
Published: July 2010

A Greek family is presented in which seven members suffered from benign hereditary chorea (a rare autosomal dominant non‐progressive chorea without dementia). All patients and three informative healthy relatives were submitted to DNA analysis using probes from loci linked to Huntington's disease. The results confirm one previous suggestion that these two disorders are not allelic and that they should be considered as two distinct genetic entities.
A family with unusual Waardenburg syndrome type I (WSI), cleft lip (palate), and Hirschsprung disease is not linked to PAX 3
Authors: Pierpont John W. , Jacques Duane St. , Seaver Laurie H. , Erickson Robert P.
Published: July 2010

An unusual family with Waardenburg syndrome type 1 (WSI), cleft lip (palate), and Hirschsprung disease is not linked to the PAX 3 gene since there is an obligate crossover which has occurred between PAX 3 DNA markers and the disorder in this family. This family may also have anticipation of the WSI traits as the proband's grandmother is nonpenetrani, his mother has dystopia canthorum, and severe cleft lip (palate), while the proband has dystopia canthorum, severe cleft lip (palate), and Hirschsprung disease. Thus, a locus other than PAX 3 is implicated in this Waardenburg‐like syndrome with Hirschsprung disease and cleft lip (palate).
Clinical and molecular genetic findings in five patients with Miller‐Dieker syndrome
Authors: Köhler A. , Hain J. , Müller U.
Published: July 2010

Five patients with type 1 lissencephaly, typical features of Miller‐Dieker syndrome and apparently normal karyotypes were investigated for microdeletions in chromosome 17p13.3. Analysis of loci D17S5 and D17S379 by polymerase chain reaction and fluorescence in situ hybridization revealed a deletion in three cases. No deletion was observed in the remaining two cases. Given the almost identical clinical picture of the five patients, the great variation in the molecular findings argues against Miller‐Dieker syndrome being a contiguous gene syndrome.
Acro‐pectoro‐renal field defect with contralateral ureteropelvic junction obstruction
Authors: Hegde Hardally R. , Leung Alexander K. C. , Robson Wm. Lane M.
Published: July 2010

Ureteropelvic junction obstruction was noted in a newborn male infant with acro‐pectoro‐renal field defect. To our knowledge, this association has not previously been reported. Ultrasonography of the urinary tract should be performed on all children with aplasia of the pectoralis major muscle.
A recombination event in the closely linked plasminogen and apolipoprotein(a) gene loci
Authors: Magnaghi Paola , Agazzi Alberto , Semino Ornella , Ferrari Maurizio , Barbui Tiziano , D'Angelo Armando , Taramelli Roberto
Published: July 2010

Genetic studies as well as in situ hybridisation data have strongly demonstrated that the genes coding for apoprotein(a) and plasminogen are linked and localised to chromosome 6 at band 6q26‐27. We describe in this report the presence of a recombination event in a region of approximately 50 kb of DNA separating the two genes. The recombination was found in an Italian family, in which a mutation affecting both plasminogen plasma level and activity of plasminogen activity has been detected. Polymerase chain reaction and sequencing analysis showed the presence of a mutation different from those previouly reported in two Japanese families.
Constitutional heteromorphism of 9q13→q21 in a patient with chronic myelogenous leukemia
Authors: Surana Rawatmal B. , Rafi Syed K. , Christopher Kevi L. , Reid Thomas J. , Weiss Raymond B.
Published: July 2010

Cytogenetic studies were carried out in a 44‐year‐old white male because of newly diagnosed chronic myelogenous leukemia. His initial bone marrow study revealed 46,XY,var(9)(q13→q21)/46,XY,var(9) (q13→q21), t(9;22)(q34;q11) karyotypes and later he also acquired a 47,XY,+8,var(9)(q13→q21), t(9;22)(q34;q11) clone. The var(9)(q13→q21) heteromorphism was observed in the normal 9 homolog, in 200 GTG‐banded bone marrow metaphases in seven cytogenetic studies (1988‐90). This heteromorphism was observed in the normal cell line, in the two chronic myelogenous leukemia‐related clones, as well as in 100 mitogen‐induced peripheral blood lymphocytes, indicating its constitutional nature. This seems to be the first report of var(9)(q13→q21) heteromorphism, involving GTG‐positive euchromatic band, in a chronic myelogenous leukemia proband.
Cystic fibrosis mutations and immotile cilia syndrome
Authors: Liechti‐Gallati Sabina , Kraemer Richard
Published: July 2010

The immotile cilia syndrome (ICS) presents with autosomal recessive inheritance and is a chronic respiratory disease supposed to be caused by different genetic determinants. The hypothesis that cystic fibrosis (CF) heterozygotes may have a predisposition to develop bronchial or respiratory diseases other than CF prompted us to look for CF mutations in patients with ICS. Five patients, as well as the parents and two healthy brothers of one patient were tested for 12 CF mutations, for the polymorphic GATT repeat in intron 6a and for the CF gene flanking markers XV‐2c, KM19, MP6d‐9, J3.11. None of the 12 mutations at the CF locus have been detected in the ICS patients and no linkage was found between ICS and the polymorphic markers. Thus, based on our data, ICS and CF seem to be two different clinical entities.
Parental origin of the X chromosome, X chromosome mosaicism and screening for “hidden” Y chromosome in 45,X Turner syndrome ascertained cytogenetically
Authors: Larsen Torben , Gravholt Claus Højbjerg , Tillebeck Annette , Larsen Hanne , Jensen Marianne Bryder , Nielsen Johannes , Friedrich Ursula
Published: July 2010

Our study confirms the finding that about 85% of X chromosomes in Turner girls are maternally derived. A new observation is the detection of a high frequency of mosaicism (15%) in Turner girls who by cytogenetic analysis were thought to have a pure 45,X karyotype. DNA examination of the material was done by hybridization with digoxigenin labelled, non‐radioactive probes, and PCR products for microsatellite analysis were run on polyacrylamide gels. We screened for the presence of “hidden” Y chromosome mosaicism, using the primers SRY, ZFY, DYZ3, DYZ1 and DYS132. Contrary to other reports using the PCR technique to unravel “hidden” Y chromosome mosaics, we did not find any positive cases. A precise technical protocol for these new techniques is given, and the advantages are discussed.
A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia
Authors: Fagerlund T. H. , Islander G. , Twetman E. R. , Berg K.
Published: July 2010

Eight mutations in the gene (the RYR1 gene) encoding the calcium release channel of sarcoplasmic reticulum (SR) in skeletal muscle are so far known to be very closely linked to malignant hyperthermia susceptibility in man and are regarded to be causative. We have examined 41 Swedish families where malignant hyperthermia had occurred in at least one member during anaesthesia, with respect to three of the known mutations. The mutations were Arg163Cys; Ile403Met and Arg614Cys (also known as the “pig mutation”). In three (i.e. 7%) of the families we detected the Arg614Cys mutation, and this was the only one of the mutations searched for that was observed. This indicates that other mutations than those searched for in this study must cause malignant hyperthermia susceptibility in most Swedish malignant hyperthermia susceptible families.
Lung hypoplasia and severe pulmonary hypertension in an infant with double heterozygosity for spondyloepiphyseal dysplasia congenita and achondroplasia
Authors: Günthard Joëlle , Fliegel Christian , Ohnacker Helmut , Rutishauser Markus , Bühler Erika
Published: July 2010

A rare instance of double heterozygosity for spondyloepiphyseal dysplasia congenita and achondroplasia is presented. Despite midface hypoplasia, thorax deformity and lung hypoplasia, the child survived the neonatal period. Severe pulmonary hypertension, already present at birth, led to right heart failure and death at the age of 1 year.
A novel insertional mutation of a single base in exon 12 of the dystrophin gene
Authors: Lasa Adriana , Gallano Pia , Colomer Jaume , Baiget Montserrat
Published: July 2010

A new point mutation in exon 12 of the dystrophin gene was identified in a DMD patient using multiple SSCP analysis, which allows the simultaneous study of several exons. The mutation is an A insertion at position 1580 of the cDNA sequence, leading to a stop codon in the translational reading frame. This mutation was not observed in a sample of 70 DMD patients.
Rett syndrome: potential gene sources ‐ phenotypical variability
Authors: Åkesson Hans Olof , Wahlström Jan , Engerström Ingegerd Witt , Hagberg Bengt
Published: July 2010

A previous genealogic study on classical Swedish Rett syndrome (RS) females documented an increased rate of common ancestry, with a high percentage originating generations ago in the same homestead. The present study, an a priori test of the first study, examines an additional 20 RS females, who were consecutively traced. Of these, no fewer than 10/19 (53%) originated from earlier defined “Rett areas”: 11/19 (58%) could even be traced to the same homestead. In two clusters, each consisting of three RS females, all six subjects were descendants of the same two couples several generations ago. Consanguineous marriages among grandparents on both sides were found to have occurred in 11% (4/37), i.e. significantly more frequently than in the average Swedish population (1%). The results of this second study confirm all points of the first. A clinical analysis of cases with common ancestral origin underlines the phenotypical variability which is often seen in interrelated RS females. We conclude that RS can appear in either its classical form or as a variant. Our genealogical data may indicate transmission starting with a premutation that over generations can result in a full mutation, probably when the parents have the premutation in a homozygous form.
The Coffin‐Siris syndrome: data on mental development, language, behavior and social skills in 12 children
Authors: Swillen Ann , Glorieux Nausikaa , Peeters Marijke , Fryns Jean‐Pierre
Published: July 2010

In this report we present data on cognitive development, language, behavior and social skills in 12 children and adolescents, nine girls and three boys, aged between 2.5 and 19 years, with Coffin‐Siris syndrome (CS). 1. Mental retardation was mild in three patients and moderate in the nine others. 2. Speech onset was severely retarded with little interest in language. In the older group (seven patients aged 7 to 19 years), language comprehension was appropriate to the mental level. 3. Gross‐motor functioning and autonomy, with the lowest score on “Task‐orientation”, were equal to the mental development. 4. Most frequently, aggressive disturbed behavior was observed, especially in the youngest children, while mixed disturbed behavior was observed in the oldest patients. Almost half of the CS patients (5/11) presented symptoms of pervasive developmental disorder, with 2/11 scoring in the pathological range. Obsessive interests, strong dependence on patterns and rituals and unusual fears were characteristic behavioral problems also when they got older.
Mosaic “tetrasomy” 8p: case report and review of the literature
Authors: Winters Jennifer , Markello Thomas , Nance Walter , Jackson‐Cook Colleen
Published: July 2010

A male infant presenting with multiple anomalies including a midline cleft palate, anasarca, hepatomegaly, pulmonary edema, agenesis of the corpus callosum, and complex congenital cardiac anomalies was found to have mosaicism for an additional chromosome that appeared (following GTG‐banding and FISH) to be a monocentric isochromosome of the short arm of chromosome 8 (46,XY/47,XY,+i(8p)). Nine other cases of mosaicism for an additional i(8p) were reviewed. Considerable phenotypic variation was noted. Consistent features were identified including agenesis of the corpus callosum, cardiac malformations, and minor facial dysmorphology. The phenotype of these patients partially overlaps those of trisomy 8 and trisomy 8p. By studying additional individuals with this condition, mosaic tetrasomy 8p may emerge as a recognizable clinical phenotype.
Chronological difference in walking impairment among Japanese group A xeroderma pigmentosum (XP‐A) patients with various combinations of mutation sites
Authors: Maeda Tomoko , Sato Kenji , Minami Hironori , Taguchi Hiroyasu , Yoshikawa Kunihiko
Published: July 2010

Almost all Japanese group A xeroderma pigmentosum (XP‐A) patients have nonsense and/or nonsense codon‐leading mutations in the XP group A (XPA) gene, and develop neurological abnormalities. Walking ability is one of the most important neuromuscular functions of the patients, because it determines their daily activities. We studied the correlation between the various combinations of mutations found by PCR‐RFLP in Japanese XP‐A patients and their chronological walking impairment. We classified these patients into six groups. Group I: A patient who was homozygous for the mutation at codon 116 in exon 3 (Type 1 mutation) could never walk unaided. Group III: Typical patients who were homozygous for the mutation at intron 3 (Type 2 mutation) could walk unaided till 7–16 years of age. Group V: Patients who were compound heterozygous for Type 2 mutation and for the mutation at codon 228 in exon 6 (Type 3 mutation) began to develop some walking difficulty at 5–13 years of age and became unable to walk at 25–28 years of age. Group VI: A patient who was homozygous for Type 3 mutation could walk unaided without any difficulty till the age of 21. The walking ability of group II and IV patients is not known yet.
Adenine phosphoribosyltransferase deficiency identified by urinary sediment analysis: cellular and molecular confirmation
Authors: Terai Chihiro , Hakoda Masayuki , Yamanaka Hisashi , Kamatani Naoyuki , Okai Mieko , Takahashi Fumiko , Kashiwazaki Sadao
Published: July 2010

Adenine phosphoribosyltransferase deficiency is an autosomal recessive purine enzyme defect that causes urolithiasis and, in severe cases, renal failure. Most homozygotes with this disorder were identified by analyses of excreted or surgically removed urinary stones, but some were identified only because they were family members of symptomatic individuals. We report here the detection of adenine phosphoribosyltransferase deficiency in two cases by routine analysis of urinary sediments. 2,8‐Dihydroxyadenine‐like spherical crystals were observed in the urinary sediment, and a diagnosis of homozygous adenine phosphoribosyltransferase deficiency was confirmed by cellular and molecular methods. A molecular diagnostic system using the polymerase‐chain reaction and single‐strand conformational polymorphism analysis proved to be a rapid and sensitive method to identify the APRT*J alleie, a common mutant allele among the Japanese people. These methods will facilitate identification of symptomatic and asymptomatic individuals with homozygous adenine phosphoribosyltransferase deficiency.
Mohr syndrome (oro‐facial‐digital syndrome II) ‐ a familial case with different phenotypic findings
Authors: Prpić Igor , Ćekada Senija , Franulović Jadranka
Published: July 2010

We report on two male siblings with an oro‐facial‐digital syndrome. The parents and two other siblings, a boy and a girl, are unaffected. The clinical findings on the reported brothers were different. Patient 1 had typical oral, facial and digital anomalies plus hypoplastic genitalia and short limbs. Clinically he had marked hypotonia, convulsions and apneic episodes. He died shortly after birth. His brother, Patient 2, had OFD features with conductive hearing loss and normal psychomental development. He did not have syndactylous reduplication of the great toes, although the toes were disproportionately large. These two patients are classified as OFD type II‐Mohr syndrome. Involvement of the central nervous system in OFD type II is noted. Different phenotypic findings could be explained as variable gene expressivity. The patients described here support the hypothesis that the clinical variability of the Mohr syndrome is even wider than previously thought.
Vascular ring leading to tracheoesophageal compression in a patient with Rubinstein‐Taybi syndrome
Authors: Shashi V. , Fryburg J. S.
Published: July 2010

Mediastinal vascular rings cause tracheoesophageal obstruction, resulting in respiratory symptoms and dysphagia in children. Although a large number of children with Rubinstein‐Taybi syndrome have frequent respiratory infections and feeding difficulties, there has been no firmly established association between this syndrome and the occurrence of vascular rings. We report on a patient with Rubinstein‐Taybi syndrome who had a vascular ring. Since there was a previous report of a similar ring in a child with Rubinstein‐Taybi syndrome, we suggest there may be an association between Rubinstein‐Taybi syndrome and vascular rings.
Genetic contributions to LDL‐C, Apo‐B and LDL‐C/Apo‐B ratio in a sample of Israeli offspring with a parental history of myocardial infarction
Authors: Friedlander Y.
Published: July 2010

One hundred and forty sibships consisting of 280 brothers and 256 sisters with a family history of myocardial infarction were investigated for the possible involvement of a major gene in the determination of LDL‐C, Apo‐B and LDL‐C/Apo‐B ratio (as a surrogate for LDL subclasses). The mean ages were 29.5 years (range 15–48) and 29.2 years (range 15–47), for brothers and sisters, respectively, and values were initially adjusted for age effects through multiple regression analysis. Results from commingling analysis indicated that for LDL‐C a single normal distribution fitted the data as well as a mixture of two distributions. For Apo‐B, a mixture of two normal distributions fitted the data significantly better than a single distribution (χ2= 7.8, df = 2, p = 0.02). For LDL‐C/Apo‐B ratio a mixture of three normal distributions fitted the data significantly better than two distributions (χ2= 9.2, df = 2, p = 0.01). A regression analysis applied to the logarithm of the sex‐and age‐adjusted mean and variance within sibship, showed no indication of a major gene involvement for LDL‐C. For Apo‐B and LDL‐C/Apo‐B ratio, mere existed, however, significant linear relationships between the logarithmically transformed means and wimin sibship variances which support the involvement of major genes. In addition, the Bartlett test applied to the data of within‐sibship variances also rejected the null hypothesis of multifactorial transmission for Apo‐B and LDL‐C/Apo‐B ratio (p < 0.0001). Lastly, the results from sib‐pair linkage analyses provided significantly positive evidence for linkage between ApoB levels and the Apo‐B Xbal restriction site.
Presymptomatic molecular diagnosis of autosomal dominant polycystic kidney disease using PKD1‐and PKD2‐linked markers in Cypriot families
Authors: Deltas C. Constantinou , Christodoulou Kyproula , Tjakouri Chrysa , Pierides Alkis
Published: July 2010

Autosomal dominant polycystic kidney disease (ADPKD), is a heterogeneous disorder, primarily characterized by the formation of cysts in the kidneys, and the late development in life of progressive chronic kidney failure. Three genes are implicated in causing ADPKD. One on chromosome 16, PKD1, accounts for 85–90% of all cases, and the PKD2 gene on chromosome 4 accounts for the remainder. A very rare third locus is still of unknown location. We used PKD1‐and PKD2‐linked polymorphic markers to make the diagnosis of ADPKD in young presymptomatic members in affected families. We showed that in young members of families where clinical diagnosis cannot be definitively established, molecular linkage analysis can assist clinicians in the diagnosis. In one family a 24‐year old had one cyst on the right kidney; however, molecular analysis showed clearly that he had inherited the normal haplotype. In another family, in one part of the pedigree there was co‐inheritance of the disease with a PKD1‐linked haplotype which originated in a non‐affected 78‐year‐old father. Analysis with PKD2‐linked markers excluded this locus. The data can be explained in one of two ways. Either this family phenotype is linked to a third locus, or the proband was the first affected person, most probably because of a novel mutation in one of her father's chromosomes. In conclusion, the combined use of markers around the PKD1 and the PKD2 locus provides more definitive answers in cases where presymptomatic diagnosis is requested by concerned families.
Midline congenital anomalies: the estimated occurrence among American Indian and Alaska Native infants
Authors: Coddington Dale A. , Hisnanick John J.
Published: July 2010

While congenital anomalies have been identified as the second leading cause of infant mortality among American Indians and Alaska Natives, limited information exists concerning the morbidity of such malformations. This study was undertaken to address this concern. Using data from the national hospital discharge database of the Indian Health Service, for the years 1980–1988, morbidity rates of seven, relatively common and easily identifiable midline malformations among liveborn infants in this minority population were estimated. The seven congenital anomalies and the estimated rates per 10000 births were: neural tube defects 8.09; oral clefts 29.03; abdominal wall defects 2.99; tracheoesophageal fistula 1.86; conotruncal heart defects 5.90; rectal atresia 3.15; and diaphragmatic hernia 3.24. Seven cases (1.1%) had two midline defects reported.
Lack of association of angiotensin‐converting enzyme (ACE). Gene insertion/deletion polymorphism with CAD in two Asian populations
Authors: Saha N. , Talmud P. J. , Tay J. S. H. , Humphries S. E. , Basair J.
Published: July 2010

Association of the insertion/deletion polymorphism of the angiotensin‐converting enzyme (ACE) gene with coronary artery disease with or without myocardial infarction (MI) was examined in a group of Chinese and Indian men in Singapore. The sample comprised an angiographically confirmed patient group of 276 Chinese and 102 Indians, of which 155 Chinese and 72 Indians had MI, and a matched healthy control group (147 Chinese and 166 Indians). The frequency of the D allele in the Chinese was 0.39 in those with CAD with MI, 0.43 in those with CAD but without MI, and 0.41 in the control group. The frequency of the D allele in Indians was 0.44 in CAD with or without MI, and 0.45 in the control group. There was no significant association of the ACE gene with CAD or MI in the Chinese or Indians, either in the entire sample or in different risk groups. The frequency of the D allele was significantly lower in the healthy Chinese and Indians than that reported in Caucasians. The association of the ACE gene with MI or CAD observed in other studies could not be confirmed in the present series of Chinese and Indians in Singapore.
Deletion of the long arm of chromosome 6: two new patients and literature review
Authors: Evers L. J. M. , Schrander‐Stumpel C. T. R. M. , Engelen J. J. M. , Hoorntje T. M. , Pulles‐Heintzberger C. F. M. , Schrander J. J. P. , Albrechts J. C. M. , Peters J. , Fryns J. P.
Published: July 2010

Two children with a partial monosomy 6q are reported: a girl with an interstitial deletion [46, XX, del(6)(q16.2q23.1)], and a boy with a terminal deletion [46, XY, del(6)(q25.1)]. Both children presented with developmental delay, facial dysmorphism and a cardiac defect. The patients have been studied using G banding and cosmid probes specific for the long arm of chromosome 6. Clinical data are compared with patients reported in the literature.
Molecular analysis of a Japanese family with Lesch‐Nyhan syndrome: identification of mutation and prenatal diagnosis
Authors: Yamada Y. , Suzumori K. , Tanemura M. , Goto H. , Ogasawara N.
Published: July 2010

Complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) causes Lesch‐Nyhan syndrome. We examined the HPRT gene mutation for prenatal diagnosis in a Japanese family. A single nucleotide substitution of C to T in exon 3 was identified by direct sequencing analysis of the HPRT gene of a Lesch‐Nyhan patient. This substitution resulted in a nonsense mutation, CGA (Arg) to TGA (stop), at codon 51. Utilizing an Xho I restriction site which was lost in the mutation as an indicator, a family study showed that the mother was heterozygous, but the grandmother normal. By the same method, prenatal genetic diagnosis was performed using chorionic villus samples (CVS), and showed that the fetus had the mutant allele.
Variable clinical expression in a family with OI type IV due to deletion of three base pairs in COL1A1
Authors: Lund Allan M. , Schwartz Marianne , Skovby Flemming
Published: July 2010

We have studied a family with autosomal dominant osteogenesis imperfecta (OI) type IV. Electrophoresis of collagen produced by cultured fibroblasts revealed a slower migrating population of collagen I. Cyanogen bromide peptide mapping localised the structural defect to the area of the αl(l)CB3 peptide. Subsequent sequencing revealed a deletion of nucleotides 1964–1966 in exon 27 of COL1A1. By means of restriction enzyme analysis, the deletion could be detected in all affected family members. This in‐frame deletion resulted in the removal of alanine‐438 and a Glu437Asp substitution in the proαl (I) collagen chain. Clinical variation was considerable among affected family members. The most consistent clinical features were reduced height and extraosseous manifestations of OI.
Frequencies of five genetic polymorphisms in coronarographed patients and effects on lipid levels in a supposedly healthy population
Authors: Régis‐Bailly Anne , Visvikis Sophie , Steinmetz Josiane , Feldmann Luc , Briançon Serge , Danchin Nicolas , Zannad Faiez , Siest Gérad
Published: July 2010

Allele frequencies of genetic polymorphisms were compared between supposedly healthy subjects and angiographically proven coronary artery disease patients. The polymorphic candidate loci investigated were the apolipoprotein (apo) B signal peptide and XbaI polymorphisms, the apo E polymorphism and two polymorphisms of lipoprotein lipase (LPL) gene: Hind/III and PvuII. Apo B signal peptide and HindIII/LPL polymorphisms showed significant differences in allele partition between cases and controls; the rare alleles of both polymorphisms were less frequent (p<0.05) in cases. We looked for associations between the polymorphisms and lipid concentration variability in a supposedly healthy population (145 men and 144 women). Apo B signal peptide, apo E and PvulII/LPL polymorphisms seem to influence some lipid metabolism parameters significantly. Apo AI and LpCIII levels were significantly different among apo B signal peptide genotypes: Del homozygotes had the highest concentrations of both variables. The e4 allele of apo E polymorphism was associated with increased concentrations of total cholesterol, LDL cholesterol and apo B. Increased LpAI:AII levels observed in E3 homozygotes (p<0.01) have not previously been reported. LpAI:AII concentration was also influenced by PvuII/LPL polymorphisms.
Genomic distribution of 5‘ TTCCA 3’ repeat motif and its diagnostic potential in human Y‐chromosome‐related anomalies
Authors: Gauri  , Bala Shasht , Ahmad Jamal , Ali Sher
Published: July 2010

We have studied genomic distribution of a simple repeat motif 5′ TTCCA 3′ derived from the DYZ1 fraction of the human Y chromosome employing restriction fragment length polymorphism and in situ hybridization techniques. This has led us to develop a synthetic DNA based genetic marker specific to human genome. Randomly selected human genomic DNA from both sexes, digested with a total of 16 restriction enzymes, hybridized with OAT20Y probe comprising four repeat units of 5′ TTCCA 3′ motif failed to reveal fragment length polymorphisms. In contrast, with most of the enzymes, several multilocus monomorphic bands and with a few enzymes, smeary signals were detected. In situ hybridization of the OAT20Y probe with human chromosomes revealed grains on the long arm of the Y chromosome, whereas the X‐chromosome and autosomes showed random distribution of the grains without any preferential labeling in the centromeric or telomeric regions. The OAT20Y probe uncovers a 3.4 kb isomorphic band exclusively in the human male DNA digested with Hae III enzyme. Using the OAT20Y probe, we have detected the presence of Y chromosome in mosaic cell populations of Turner's patients with dysgenetic gonads and high levels of LS/FSH. The presence of Y chromosome in these patients has been associated with an increased risk of gonadoblastoma. The OAT20Y probe offers sensitivity and accuracy for the detection of Y‐chromosome‐bearing cells in a mosaic cell population and, consequently, help in better management of the patients.
Autosomal recessive retinitis pigmentosa in Spain: evaluation of four genes and two loci involved in the disease
Authors: Bayés M. , Marímez‐Mir A. , Valverde D. , del Río E. , Vilageliu L. , Grinberg D. , Balcells S. , Ayuso C. , Baiget M. , Gonzàlez‐Duarte R.
Published: July 2010

Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous form of retinal degeneration. The genes for the β‐subunit of rod phosphodiesterase (PDEB), rhodopsin (RHO), peripherin/RDS (RDS) and the rod outer segment membrane protein 1 (ROM1), as well as loci at 6p and 1q, have previously been reported as the cause of ARRP. In order to determine whether they are responsible for the disease in Spanish pedigrees, linkage and homozygosity studies using markers at these loci were carried out on 47 Spanish ARRP families. SSCP analysis was performed to search for mutations in the genes cosegregating with the disease in particular pedigrees. Three homozygous mutations in the PDEB gene were found, thus accounting for 6% of the cases. No other disease‐causing mutation was observed in the other genes analysed, nor was significant evidence found for the involvement of the loci at 6p or 1q. On the basis of these data, it is unlikely that these genes and loci account for a considerable proportion of ARRP cases.
Unbalanced karyotype, dup 14(q13‐q22), in a mother and her two children
Authors: Pot M. L. H. , Giltay J.C. , van Wilsen A. , Breslau‐Siderius E. J.
Published: July 2010

A duplication of chromosome 14(q13‐q22) caused mild mental retardation and some dysmorphic features in two children and their mother. The unbalanced karyotype did not affect the fertility of the mother. Fluorescent in situ hybridization, with a chromosome 14 specific paint, was used to confirm that the inserted material was from chromosome 14.
Short stature, moderate mental retardation, hyperactivity, facial dysmorphism, skeletal abnormalities, and exaggerated ketosis: a new syndrome
Authors: Boneh Avihu , Glick Benjamin , Gutman Alisa , Mogle Paul
Published: July 2010

We describe three siblings who presented with short stature, hyperactivity, delayed speech and moderate psychomotor retardation. In addition, they had dysmorphic features, a peculiar combination of skeletal abnormalities, small kidneys and exaggerated fasting ketosis. We suggest that they represent a new syndrome. The possibility of end‐organ receptor failure is suggested.
De novo direct tandem duplication of a small segment of the short arm of chromosome 7 (p21.22→22.1)
Authors: Franz H. B.G. , Schliephacke M. , Niemann G. , Mielke G. , Backsch C.
Published: July 2010

We report a boy with duplication of a small segment of the short arm of chromosome 7 (46, XY, dir dup (7) (p21.2→22.1). The boy presented with supravalvular pulmonary stenosis, atrial septum defect and mental retardation. The origin of the additional material from chromosome 7 was confirmed by fluorescence in situ hybridization. This technique in combination with the use of single‐copy DNA probes may in future help to delineate the phenotype/karyotype correlation.