bluuebunny/crossref_metadata_2025 huggingface dataset:
The Niikawa‐Kuroki (Kabuki make‐up) syndrome in a Moslem Arab child
Authors: Gillis R. , Klar A. , Gross‐Kieselstein E.
Published: July 2010

The Niikawa‐Kuroki “Kabuki Make‐Up” syndrome is a rare sporadic malformation syndrome, characterised by severe psychomotor and growth retardation, peculiar facies, including long palpabral fissures and large malformed ears and skeletal abnormalities. We report a 2‐year‐old Moslem Arab boy with 28 of the 32 originally described features of this syndrome and in addition with hyperelastic joints, hypospadias and scaphocephaly which were not previously described in association with the Kabuki make‐up syndrome. This is the fifth reported case of this syndrome in a non‐Japanese patient, and the second reported case in a patient of Arab descent.
Association of DNA‐haplotypes in the human LDL‐receptor gene with normal serum cholesterol levels
Authors: Schuster H. , Humphries S. , Rauh G. , Held C. , Keller Ch. , Wolfram G. , Zöllner N.
Published: July 2010

For the low density lipoprotein receptor (LDLR), many mutations have been characterized which identify this gene as one with an important role in lipid metabolism in patients with familial hypercholesterolemia (FH). Genetic heterogeneity at this locus raises the possibility that the LDLR may also contribute to variation in cholesterol levels in the normocholesterolemic population. We have determined genotypes at the LDLR locus using restriction fragment length polymorphisms (RFLPs) detected with the enzymes StuI, ApalI, PvuII and NcoI in 324 normocholesterolemic individuals from Germany. A significant association (p<0.01) was detected between the cutting site for the PvuII RFLP and lower cholesterol levels, and variation associated with this polymorphism explains 3% of the sample variance in cholesterol levels. In family studies we have determined four‐RFLP haplotypes of 148 independent LDLR genes and have observed 9 haplotypes in the population. Three of these haplotypes containing the cutting site for PvuII are associated with a reduction in plasma LDL‐cholesterol levels. Phylogenetic analysis indicates that these three haplotypes are related by evolutionary history, and this suggests that a single functionally important sequence change in the LDLR explains our observations. Our data confirm other reports and strongly suggest that the LDLR locus may be one of those genes involved in determining serum cholesterol levels in the normal population.
A possible relationship between Beckwith‐Wiedemann syndrome, urinary tract anomaly and prune belly syndrome
Authors: Watanabe Hiroshi , Yamanaka Tatsuhiro
Published: July 2010

We report here two siblings diagnosed as having Beckwith‐Wiedemann syndrome. In addition to Beckwith‐Wiedemann syndrome, one of the siblings was also diagnosed with prune belly syndrome. The other sibling suffered from obstructive uropathy and unilateral cryptorchidism, which are also seen in prune belly syndrome. We believe that these two cases point to a potential association between Beckwith‐Wiedemann syndrome, prune belly syndrome, and urinary tract anomaly.
Excess of HLA parental sharing in families with Turner patients
Authors: Cuccia M. , Martinetti M. , Larizza D. , Bolis P. F. , Severi F.
Published: July 2010

In utero selection processes are probably related to mother–father compatibility as has been reported in abortion‐prone couples and in Down syndrome studies. In order to analyse this phenomenon, we investigated families with chromosomal imbalance (Turner syndrome). We chose this model because previous data indicated a high frequency of HLA‐A31 and B38 in Turner patients and in their mothers. We report high HLA antigen sharing in Turner families and great histocompatibility between mother and affected daughter, not related to abortion histories. The proportion of HLA‐A homozygous cases among Turner children was higher than expected. The level of lymphocytotoxic antibodies against fetus in mothers of Turner patients was comparable to that of mothers of families with normal fertility and probably favoured these pregnancies.
Emery‐Dreifuss syndrome in three generations of females, including identical twins
Authors: Ørstavik Karen Helene , Kloster Reidar , Lippestad Carl , Rode Lars , Hovig Torstein , Fuglseth Kari Nissen
Published: July 2010

Emery‐Dreifuss syndrome is characterized by early contractures, slowly progressing muscle wasting and cardiomyopathy, often presenting as heart block. The syndrome is usually inherited as an X‐linked recessive. We present a family with four affected females in three generations, including a pair of identical twins. All patients developed elbow contractures, scoliosis, and stiffness of the spine and neck from the age of about 10, with little progression in later years. The proband developed cardiomyopathy at the age of 45, whereas her mother died at 41 without a confirmed diagnosis of cardiomyopathy. The twin daughters of the proband had no unequivocal signs of cardiomyopathy at the age of 21 years. Early recognition of this syndrome is important because of the possible development of heart block.
Clinical expression of Menkes syndrome in females
Authors: Gerdes A.‐M. , Tønnesen T. , Horn N. , Grisar T. , Marg W. , Müller A. , Reinsch R. , Barton N. W. , Guiraud P. , Joannard A. , Richard M. J. , Güttler F.
Published: July 2010

Three female patients with Menkes syndrome are described. Clinically, they have typical Menkes syndrome. Biochemically, they have significantly increased 64Cu‐uptake in cultured fibroblasts. The chromosomal analysis was normal for two of the patients and abnormal for one patient (45X/46XX mosaicism).
Re‐evaluation of GM2346 from a del(16)(q22) to t(4;16)(q35;q22.1)
Authors: Callen D. F. , Baker E. G. , Lane S. A.
Published: July 2010

Reassessment of the cytogenetics of a patient previously karyotyped as del(16)(q22) demonstrates the presence of a balanced translocation, t(4;16)(q35;q22.1). This patient should not be included in any future comparison involving the clinical features of patients with deletions of the long arm of chromosome 16.
Diagnosis of familial amyloidotic polyneuropathy in France
Authors: Satier F. , Nichols W. C. , Benson M. D.
Published: July 2010

Two cases of familial amyloidotic polyneuropathy (FAP) in a French family are reported. Clinical onset was in the fifth and sixth decades with decreased sensation in the lower limbs followed by involvement of the upper extremities. Motor changes appeared later and evolved to restrict ambulation. Cardiac involvement with congestive heart failure and arrhythmias was the cause of death. DNA analysis was performed on ten members of this family. Restriction enzyme analysis of amplification products of exons 2, 3 and 4 of the prealbumin gene were negative for the methionine‐30, alanine‐60 and serine‐84 mutations but positive for the tyrosine‐77 mutation. The tyrosine‐77 prealbumin mutation was first described in a family from Illinois with origin in Germany. The discovery of the tyrosine‐77 gene in the family from Picardy may help to determine the origin of this disease and tell us if one mutation has been spread around the world, as we suspect, with many kindreds having the methionine‐30 gene, or whether there have been separate spontaneous mutational events, perhaps a peculiarity of this site in the prealbumin gene.
A cost‐benefit analysis of prenatal diagnosis by amniocentesis in Denmark
Authors: Goldstein Henri , Philip John
Published: July 2010

A cost‐benefit analysis of amniocentesis has been performed using both the excess‐cost‐ and the replacement methods and several replacement and discount rates. In Denmark, amniocentesis is offered free of charge to various groups of pregnant women at risk for genetic disorders of the foetus. Most important is age ≥ 35 years. The analysis is based on incidence and survival rates for Down syndrome (trisomy 21), Patau's syndrome (trisomy 13) and Edwards' syndrome (trisomy 18), and on incidence and survival rates of children with neural tube defects. If amniocentesis were offered to all pregnant women independent of age, with a supposed participation rate of 75% and if only tangible costs and benefits were included, the analysis shows a benefitxost ratio greater than 1.0 using discount rates of 4% and 7% (both for the excess‐cost‐ and replacement method); a benefitxost ratio less than 1.0 is found using 10%. The ratio is approximately 1.0, if pregnant women aged 15–19 and 20–24 years are excluded, using the discount rate 10%. Calculations for other participation rates have also been performed. If intangible costs and benefit are included, the results are uncertain.
Batten's disease: failure of allogeneic bone marrow transplantation to arrest disease progression in a canine model
Authors: Deeg H. Joachim , Shulman Howard M. , Albrechtsen Dagfin , Graham Ted C. , Storb Rainer , Koppang Nils
Published: July 2010

We investigated whether the course of canine ceroid lipofuscinosis (CCL), a model of Batten's disease in man, was affected by allogeneic bone marrow transplantation. Four English setters with CCL, 4 months of age, were given 9.2 Gy of total body irradiation, followed by the infusion of bone marrow cells from healthy DLA identical sibling donors. All transplanted dogs had complete hematologic reconstitution. However, at 12–13 months posttransplant, all dogs developed characteristic and progressive signs of CCL. Autopsies revealed cerebral atrophy and findings of ceroid storage not different from those in non‐transplanted controls. These findings suggest that bone marrow cells do not contain or release the gene product(s) necessary to correct the disease. It appears unlikely that with our current knowledge, allogeneic marrow transplantation would be beneficial in the treatment of Batten's disease.
Detection of mitochondrial DNA deletions in blood using the polymerase chain reaction: non‐invasive diagnosis of mitochondrial myopathy
Authors: Poulton J. , Deadman M. E. , Turnbull D. M. , Lake B. , Gardiner R. M.
Published: July 2010

Southern hybridisation demonstrates deleted mitochondrial DNAs (mtDNAs) in muscle but not in blood in a subgroup of patients with mitochondrial myopathy. The polymerase chain reaction (PCR) was used to search for low levels of rearranged mitochondrial DNAs in blood in 24 patients with mitochondrial myopathy, and 15 asymptomatic relatives, all of whom have no detectable abnormality on restriction enzyme analysis of blood mitochondrial DNA. In eight patients and two of their relatives, PCR products were obtained consistent with deletions of mitochondrial DNA. The presence or absence of a deletion was correctly predicted in 10 out of 11 patients from whom information was available from muscle DNA. No false positives were obtained in 43 controls. PCR analysis of blood may be applicable as a non‐invasive screening test of affected individuals and in carrier detection.
Anthropometric study with emphasis on hand and foot measurements in the Prader‐Willi syndrome: sex, age and chromosome effects
Authors: Butler Merlin G. , Haynes Judy L. , Meaney F. John
Published: July 2010

Age, sex and chromosome effects on weight, height, sitting height, three head dimensions, and five hand and three foot measurements were analyzed from 57 patients (35 males and 22 females) with the Prader‐Willi syndrome (PWS). No significant differences were observed in anthropometric data between PWS patients with the 15q chromosome deletion and those with normal chromosomes. Preschool children were found to have dolichocephaly, while hand and foot measurements, stature and sitting height were within normal range, although foot size was smaller than hand size in females when compared with PWS males. However, anthropometric measurements, excluding weight, head length and ankle breadth, were less than—2 SD in adult patients. Abnormal growth patterns apparently exist with significant negative correlations with age, particularly in PWS males, for height, sitting height, head circumference, and hand and foot measurements, but a significant positive correlation for weight was found in patients below 10 years of age.
Routine applications of DNA fingerprinting with the oligonucleotide probe (CAC)5/(GTG)5
Authors: Neitzel H. , Digweed M. , Nürnberg P. , Pöpperl A. , Schmidt C. A. , Tinschert S. , Sperling K.
Published: July 2010

The use of DNA fingerprinting with synthetic oligonucleotides is illustrated for practical applications familiar in clinical diagnostics: pre‐ and postnatal zygosity determination and the monitoring of bone marrow transplantation. A simple method for non‐radioactive detection is described which may be interesting for many diagnostic laboratories.
Using the polymerase chain reaction to maintain DNA probe inventories in clinical and diagnostic laboratories
Authors: Tarleton Jack , Schwartz Charles E.
Published: July 2010

Clinical and diagnostic DNA laboratories must maintain a large inventory of DNA probes for use in hybridization studies. The preparation of plasmid DNA and isolation of DNA fragments for use as probes is both expensive and time consuming. We present here a rapid and relatively inexpensive method of producing large amounts of DNA fragments from stocks, using the polymerase chain reaction (PCR). Our experience over the past year using this technique has been very positive and we believe many laboratories could benefit by employing such a laborsaving approach to maintaining DNA probes. The technique uses the bacteriophage M13 DNA sequencing primers to amplify cloned inserts contained in commonly used plasmid vectors. As examples, we illustrate the use of DNA produced in this manner as probes for linkage analysis of the fragile X syndrome and for detection of deletions in the Duchenne muscular dystrophy gene. We have also found that at least two probes can be amplified in the same PCR reaction, allowing the detection of two different restriction fragment length polymorphisms (RFLP) simultaneously. It should be possible for laboratories to devise strategies particular to their individual needs using more than one DNA probe produced in the same PCR reaction to detect RFLP's. Such strategies would need only to consider that the predicted alleles of the multiple polymorphisms do not migrate to the same position during electrophoresis. Stocks of single or multiple probes produced by the PCR could then be maintained for more rapid Southern analyses.
Short arm deletion of chromosome 1: del(1)(p13.3 p22.3) in a female infant with an extreme tetralogy of Fallot
Authors: Tabata Hiroshi , Sone Katsuhiko , Kobayashi Toshihiro , Yanagisawa Takayuki , Tamura Tadahisa , Shimizu Nobuzou , Kanbe Yuzuru , Tashiro Masahiko , Ono Sanayasu , Kuroume Takayoshi
Published: July 2010

High‐resolution chromosome analysis showed the karyotype 46,XX,del(1)(p13.3 p22.3) in a female infant with an extreme tetralogy of Fallot and multiple congenital anomalies. The patient showed characteristic features: upper and lower eyelids connected to each other by a string‐like epithelium, low hairline, epicanthal folds, saddle nose with a broad, flat root, micrognathia, short neck, high‐arched palate, prominent xiphisternum, wide‐spaced nipples, bilateral pes equinovarus, fifth toes that overlapped the fourth toes bilaterally, a deep fissure between the first and second toes bilaterally, and abnormal flexions of fingers and toes. Growth and psychomotor retardation were also noted. Cardiac catheterization revealed an extreme tetralogy of Fallot complicated by a patent ductus arteriosus. Ventricular tachycardia and ventricular premature beats developed during the neonatal period and did not respond well to anti‐arrhythmic drugs. She died of the anoxia caused by closure of the patent ductus arteriosus when she was 7 months old.
Trisomy 18 and 18p‐ features in a case of isochromosome 18q [46,XY,i(18q)]: prenatal diagnosis and autopsy report
Authors: Wurster‐Hill Doris H. , Marin‐Padilla J. Miguel , Moeschler John B. , Park Jonathan P. , McDermet Melanie
Published: July 2010

This paper reports the prenatal diagnosis and autopsy findings of a case of true isochromosome 18q [46,XY,i(18q)] with severe cephalic malformations. Comparison is made with other cases of i(18q).
Atypical facio‐scapulo‐humeral muscular dystrophy — a counselling dilemma
Authors: Reardon W. , Temple I. K. , Harwood G. , Baraitser M.
Published: July 2010

In an isolated male patient, differentiation between Facio‐Scapulo‐Humeral Muscular Dystrophy (FSH) and Becker Muscular Dystrophy (BMD) may be difficult. To emphasise this point, we report a patient, whose features are atypical of FSH. Details of his daughter who now manifests similar presenting features, are provided. The pitfalls posed for the genetic counsellor by FSH presenting in an atypical manner which clinically overlaps with genetically distinct conditions are discussed in the light of this pedigree.
The ancestry of spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL) in South Africa
Authors: Torrington M. , Beighton P.
Published: July 2010

Comprehensive genealogical investigations have been undertaken in eight families in the Afrikaans‐speaking community of South Africa, in which at least one person had spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL). All eight families had ancestral links with two females. These women had multiple marriages and cohabitations during the late 17th and early 18th centuries and they were 12 generations removed from the affected individuals. The identification of these common progenitors confirmed the syndromic homogeneity of SEMDJL in South Africa and permitted recognition of numerous obligate heterozygotes, thus facilitating biomolecular investigations of the basic defect.
Familial Jarcho‐Levin syndrome
Authors: Romeo M. G. , Distefano G. , Bella D. Dt , Mangiagli A. , Caltabiano L. , Roccaro S. , Mollica F.
Published: July 2010

Jarcho‐Levin syndrome is a variety of autosomal recessive spondylocostal dysostosis characterized by severe deformity of the thoracic cage, leading to respiratory failure and early death. There are often associated dysmorphic features. The disease is more frequent in Puerto Ricans and rare in Europe. A Sicilian family with four affected individuals in two interrelated sibships is reported.
Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome)
Authors: Salonen R. , Somer M. , Haltia M. , Lorentz M. , Norio R.
Published: July 2010

We describe 14 patients, from 11 families, who have a progressive encephalopathy with early onset. The clinical signs of the disease are severe hypotonia, convulsions with hypsarrhythmia, profound mental retardation, hyperrcflexia, transient or persistent edema, and optic atrophy. These findings and the characteristic dysmorphic features allow recognition of these patients, although no basic metabolic defect has been found. Microcephaly and atrophy of the brain develop, especially in the cerebellar and brain stem areas. An autosomal recessive mode of inheritance is likely.
Transcobalamins in the etiology of neural tube defects
Authors: Magnus Per , Magnus Erik M. , Berg Kåre
Published: July 2010

In a sample of 79 pregnant women at risk of having offspring with neural tube defects (NTDs) and 158 controls, significantly increased median values were found for apo‐transcobalamins I and II in amniotic fluid in the group at risk, thus confirming previous results. The findings may reflect a genetic disposition to NTDs associated with altered levels of apo‐transcobalamins, and research on the etiology and mechanisms of NTDs should focus on these proteins.
Importance of accurate diagnosis in counseling for neural tube defects diagnosed prenatally
Authors: Steinhaus Kathryn A. , Bernstein Renée , Bocian Maureen E.
Published: July 2010

In cases of fetal neural tube defects (NTD), termination of pregnancy without ascertainment of specific etiology may lead to provision of incorrect recurrence risks and erroneous diagnosis in future pregnancies. Four patients are presented who illustrate the etiologic diversity of neural tube defects. The patients were referred for prenatal diagnosis because of elevated maternal serum alphafetoprotein (AFP). All four chose pregnancy termination. Diagnostic methods included fetal ultrasound, amniocentesis for fetal karyotyping and amniotic fluid AFP/acetyl‐cholinesterase (AChE) and/or fetal karyotyping after delivery, and dysmorphology evaluation of the fetus after intact delivery. These cases highlight the benefits of fetal karyotype analysis and of an intact delivery and thorough clinical examination of the fetus when patients choose to terminate pregnancies with fetal anomalies.
DNA deletions in the low density lipoprotein (LDL) receptor gene in Danish families with familial hypercholesterolemia
Authors: Rüdiger N. S. , Heinsvig E. M. , Hansen F. A. , FÆrgeman O. , Bolund L. , Gregersen N.
Published: July 2010

DNA samples from 25 unrelated Danish patients with familial hypercholesterolemia (FH) were screened by Southern blot hybridization to detect gross alterations in the low density lipoprotein (LDL) receptor gene. Three FH‐patients were found to have a deletion. Two of these delete part of the cysteine rich domain, which comprises the ligand binding region of the LDL‐receptor. The third deletion encompasses coding regions for the cytoplasmic part of the receptor. As two of these deletions could be equivalent to previously described LDL‐receptor gene alterations, these data seem to support a notion of recombination hot spots which involve Alusequences.
Prenatal diagnosis of lethal osteogenesis imperfecta in twin pregnancy
Authors: Morin L. R. M. , Herlicoviez M. , Loisel J. C. , Jacob B. , Feuilly C. , Stanescu V.
Published: July 2010

Lethal osteogenesis imperfecta was diagnosed at 27 weeks amenorrea in one fetus of a bichorial twin pregnancy. Sonographic findings included: short‐limb dwarfism, hypotrophy and hypoechoic bones. The affected fetus was so translucent that only the normal fetus could be seen on plain in utero radiography. The affected fetus died immediately after birth. Postmortem radiography and histology were typical of lethal osteogenesis imperfecta of type IIA. Aids to the etiological diagnosis of in utero dwarfism are presented. Sonographic features correlated with neonatal death are described.
The inheritance of conotruncal malformations: a review and report of two siblings with tetralogy of Fallot with pulmonary atresia
Authors: Wulfsberg Eric A. , Zintz Eric J. , Moore John W.
Published: July 2010

Congenital heart defects (CHD) are a group of structural abnormalities that in humans have a combined incidence of approximately 1%. It is estimated that 4–5% of CHD are associated with chromosome abnormalities, 1–2% are associated with single gene syndromes, 1–2% are due to known teratogens, with the rest presumably determined multifactorially. We report on a brother and sister with tetralogy of Fallot with pulmonary atresia, and review the inheritance of familial conotruncal anomalies. We feel the small number of family clusters and the rare instances of consanguinity in non‐syndromal conotruncal defects are consistent with multifactorial determination. While it is prudent in counseling families with 2 or more individuals with conotruncal CHD to raise the possibility of single gene inheritance, we believe that current empiric recurrence risk estimates most accurately reflect their risks.
A simplified protocol for fluorescence in situ hybridization with repetitive DNA probes and its use in clinical cytogenetics
Authors: Bartsch O. , Schwinger E.
Published: July 2010

A method for chromosome‐specific staining and its use in clinical cytogenetics is described. This fluorescence in situ hybridization protocol for repetitive DNA probes results in yellow‐green fluorescent signals on orange‐red stained chromosomes. Special characteristics are its simplicity, the use of digoxigenin‐11‐dUTP for labeling, and the combination of high stringency criteria for hybridization and low stringency for washing. The method is particularly advantageous in cases with structurally abnormal extra chromosomes (ESACs), marker chromosomes of gonosomal origin, and chromosomal mosaicism. It may also facilitate the screening of cases for fragile X. The chromosome‐specific staining can be done within 1 working‐day.
Trembling chin — a report of this inheritable dominant character in a four‐generation Canadian family
Authors: Alsager Dale E. , Bowen Peter , Bamforth J. S.
Published: July 2010

Trembling chin is an unusual, benign, dominant trait. We describe the condition in a fourgeneration Canadian family. Investigations, which included E.E.G., electromyograph and facial nerve conductance studies on affected and unaffected individuals, were normal. Premature hearing loss, present in all affected members of this family over age 50, strongly suggests an association of trembling chin with otosclerosis. The merits of early diagnosis and preventive treatment for otosclerosis in persons affected by trembling chin are discussed.
Enhancement of amniotic fluid cell growth for genetic amniocentesis
Authors: Mathews Thomas , Verma Ram S.
Published: July 2010

The last two decades have witnessed a logarithmic growth in demand for prenatal diagnosis of human disease through amniocentesis. Consequently, culture turn‐around‐time has become the major concern of all those who are primary care providers for patients seeking help. We report a rapid method for obtaining cytogenetic results from amniocytes as early as 5 days. Early tapping and reducing the turn‐around‐time during cytogenetic analysis may provide an alternative to chorionic villi sampling.
EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) with a balanced reciprocal translocation between 7q11.21 and 9p12 (or 7p11.2 and 9q12) in three generations
Authors: Hasegawa Tomonobu , Hasegawa Yukihiro , Asamura Shinji , Nagai Toshiro , Tsuchiya Yutaka , Ninomiya Makoto , Fukushima Yoshimitsu
Published: July 2010

Familial cases (a grandfather, a father and a daughter) of the EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) are reported. All of them have a balanced reciprocal translocation (46,XY or XX, t(7;9) (q11.21;p12) or (46,XY or XX, t(7;9) (p11.2;q12)), but no other members of the family have either the EEC syndrome or chromosome abnormalities. This indicates that one of the chromosome sites 7q11.21, 9p12, 7p11.2 and 9q12 is a candidate for gene locus of the EEC syndrome.
Nine mutations in the cystic fibrosis (CF) gene account for 80% of the CF chromosomes in French patients
Authors: Simon‐Bouy B. , Mornet E. , Serre J. L. , Taillandier A. , Boué J. , Boué A.
Published: July 2010

Thirteen mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been screened in a French sample of 185 cystic fibrosis (CF) patients, together with their respective associated RFLP haplotypes at the linked D7S23 locus (XV2C and KM19 markers). The respective frequencies of the mutations showed that 9 of them account for 80% of the CF chromosomes. Implications for prenatal diagnosis and heterozygote detection are defined and discussed. The well‐known great excess of RFLP B marker within CF chromosomes is partially explained by two already characterized mutations highly associated with haplotype B: ΔF508 and G542X. Similarly, the excess of haplotype D within CF chromosomes is partially explained by the association between ΔI507 and this haplotype. These results may suggest the existence of two still untested or uncharacterized mutations, whose frequencies could be near 1%, one which would be associated with haplotype B and a second which would be associated with haplotype D. The possible cause of the specific association between most of the main different CF mutations and the RFLP haplotype B is discussed.
Two Japanese cases with aspartylglycosaminuria: clinical and morphological features
Authors: Yoshida Kunihiro , Ikeda Shu‐Ichi , Yanagisawa Nobuo , Yamauchi Toyoaki , Tsuji Shoji , Hirabayashi Yoshio
Published: July 2010

Two members of a consanguineous Japanese family with a clinical picture of aspartylglycosaminuria (AGU) are described. Both patients exhibited mental retardation, coarse facial features, angiokeratoma and myoclonic seizures. Biochemical studies showed elevated excretion of urinary sialyloligosaccharides and decreased activity of aspartylglycosaminidase in lymphoblasts. Morphologic studies of skin biopsy specimens showed many clear vacuoles mainly in the vascular endothelial cells and secretory cells of the sweat glands. Osmiophilic lamellar cytoplasmic inclusions were also noted in the ganglion cells in rectal biopsy. The ethnic distribution of AGU may be more widespread than previously suspected and appears not to be restricted to Finnish populations. Ours are the first Japanese patients diagnosed as AGU. We conclude that AGU should also be included in the differential diagnosis of mentally retarded patients in Asian countries.
Nasopalpebral lipoma‐coloboma syndrome
Authors: Akarsu A. N. , Sayli B. S.
Published: July 2010

An autosomal dominant dysplasia‐malformation syndrome affecting seven individuals in one family is reported. The components of the syndrome include congenital nasopalpebral lipoma, telecanthus, and bilateral colobomas of upper and lower lids without midface hypoplasia. It appears to be the second recorded example resulting from an autosomal dominant gene fully penetrant in both sexes.
An autosomal recessive form of benign familial neonatal seizures
Authors: Schiffmann Raphael , Shapira Yehuda , Ryan Stephen G.
Published: July 2010

We present a consanguineous sibship with benign familial neonatal seizures. The mode of transmission of the disorder in this family seems to be autosomal recessive, which is contrary to the usual autösomal dominant type. Linkage analysis failed to show tight linkage between the disease locus and the autosomal dominant locus assigned to chromosome 20q. We thus conclude that benign familial neonatal seizures is a genetically heterogeneous type of epilepsy.
Linkage analysis in properdin deficiency families: refined location in proximal Xp
Authors: Wadelius Claes , Pigg Maritta , Sundvall Mats , Sjöholm Anders G. , Goonewardena Ponmani , Kuijper Ed J. , Tijssen Cees C. , Jansz Anton , Späth Peter J. , Schaad Ulf B. , Tranebjaerg Lisbeth , Nielsen Hans E. , Söderström Claos , Annerén Göran , Pettersson Ulf
Published: July 2010

Properdin is a component of the alternative activation pathway of the complement system. Deficiency or dysfunction of the protein is inherited in an X‐linked recessive manner. Affected males have an increased risk of developing meningococcal disease. Six multi‐generation families with different types of properdin deficiency were analyzed using microsatellite and other polymorphisms on the X chromosome. Based on multipoint data, it was found that the disease gene maps close to DXS255 (Zmax= 13.3 at θmax= 0.00) and DXS426 (Zmax= 12.9 at θmax= 0.00) on the Xp‐arm near the centromere. There was no indication of genetic heterogeneity among the six families analyzed. Thus it is now possible to perform accurate DNA‐based determination of the inheritance of the mutation in affected families.
Consanguineous marriages among parents of Down patients
Authors: Başaran Nurettin , Cenani A. , Şayli B. S. , Özkinay C. , Artan S. , Seven H. , Başaran A. , Dinçer S.
Published: July 2010

In order to reveal if there is an effect on the genesis of meiotic‐ or early zygotic non‐disjunctions, data related to 1598 Down syndrome patients from 1578 families studied in five different genetic centers in Turkey are reported. Parental consanguinity and the inbreeding coefficient were found to be lower among patients of 21‐trisomics than in parents without Down offspring. It was concluded that available information does not support the presence of a “non‐disjunction gene” in man.
Congenital hypertrophy of retinal pigment epithelium in patients with colonic polyps associated with cancer family syndrome
Authors: Houlston R. S. , Fallon T. , Harocopos C. , Williams C. B. , Davey C. , Slack J.
Published: July 2010

Congenital hypertrophy of retinal pigment epithelium (CHRPE) has been shown to be a frequent extracolonic manifestation of adenomatous polyposis coli (APC). The presence of CHRPE in patients with adenomatous polyps from families with cancer family syndrome suggests possible involvement of the APC gene locus in syndromes associated with less florid polyp formation than seen in APC. It also emphasises that caution must be exercised in using the presence of CHRPE clinically as a marker for APC in isolated at‐risk individuals.
Congenital heart defects, hamartomas of the tongue and polysyndactyly in a sister and brother
Authors: Örstavik Karen Helene , Lindemann Ralf , Solberg Lars Åge , Foerster Arnold , Sørland Svein Jan
Published: July 2010

We report a sister and brother with congenital heart defects, hamartomas of the tongue and polydactyly. Both had coarctation of the aorta, which was repaired in early infancy. In addition, the girl had atrioventricular canal. She died postoperatively at age 4 years. The boy had subaortic stenosis and died of pneumonia at age 2 years. Both children had normal psychomotor development. The parents were healthy and unrelated. The familial occurrence could be due to a previously unrecognized autosomal recessive syndrome or parental gonadal mosaicism for a dominant syndrome.
Variable dystrophin expression in different muscles of a Duchenne muscular dystrophy carrier
Authors: Muntoni Francesco , Mateddu Anna , Marrosu Maria Giovanna , Cau Miiena , Congiu Rita , Melis Maria Antonietta , Cao Antonio , Cianchetti Carlo
Published: July 2010

The majority of Duchenne muscular dystrophy (DMD) female carriers show dystrophin immunostaining abnormalities, although a significant proportion of clinically non‐manifesting carriers are normal following this analysis. We had the opportunity to study dystrophin immunostaining in two different muscles, the vastus lateralis and the rectus abdominis of a possible DMD carrier. While the vastus showed normal dystrophin immunostaining, pathological staining was detected in her rectus abdominis. These findings seem to indicate that dystrophin expression can vary in different muscle groups of a DMD carrier. The implications of these findings in DMD carrier detection and possible dystrophin function are discussed.
Ring Y chromosome: cytogenetic and molecular characterization
Authors: Wegner Rolf‐Dieter , Scherer Gerd , Pohlschmidt Marita , L'Allemand Dagmar , Gal Andreas
Published: July 2010

A female patient with Turner syndrome and the karyotype mos45,X/46,X,r(Y)/46,XY is described. Physical mapping of the ring chromosome by Y‐specific single‐copy and moderately repeated DNA sequences as molecular probes showed that, in addition to the heterochromatic part of Yq, a considerable portion of the Yp has also been lost in the course of the rearrangement. Thus, molecular findings provide independent support that this structurally abnormal sex chromosome is a ring Y and agree with the generally accepted model of ring formation requiring breaks in both chromosome arms. Clinical consequences of Y chromosome mosaicism in patients with Turner syndrome are discussed.
Typical and partial cat eye syndrome: identification of the marker chromosome by FISH
Authors: Liehr T. , Pfeiffer R. A. , Trautmann U.
Published: July 2010

Three children are reported with typical cat eye syndrome (CES) and three more children with partial CES because of absence of coloboma, in which the supernumerary marker chromosome was studied by FISH. Using a genomic library, and also a centromeric and particularly a cosmid probe of 22q11, partial tetrasomy was shown in all cases.
Congenital hypoparathyroidism, seizure, extreme growth failure with developmental delay and dysmorphic features—another case of this new syndrome
Authors: Kalam M. A. , Hafeez W.
Published: July 2010

A 4‐year‐old Saudi female child with extreme failure to thrive, striking dysmorphic features, developmental delay, congenital hypoparathyroidism, UTI. seizures, chronic otitis media, chronic non‐specific gastroenteritis and repeated life‐threatening infections was followed from birth. She was the product of first‐cousin consanguineous marriage. She had striking facies with frontal prominence, deep‐set eyes, depressed nasal bridge, beaked nose, long philtrum with thin upper lip, micrognathia, large floppy ears, bifid uvula, and growth retardation with SD score < — 2 for height, weight and head circumference. We believe these features which include congenital hypoparathyroidism, severe growth failure and developmental delay in the absence of chromosomal abnormality represent a newly described genetically determined syndrome.
Pseudohypoparathyroidism type I and Albright's hereditary osteodystrophy with a proximal 15q chromosomal deletion in mother and daughter
Authors: Hedeland Hans , Berntorp Kerstin , Arheden Kristina , Kristoffersson Ulf
Published: July 2010

A 33‐year‐old woman and her 71‐year‐old mother were both found to have pseudohypoparathyroidism type I with Albright's hereditary osteodystrophy associated with a cytogenetic deletion of the proximal part of one chromosome 15, resembling that found in Prader‐Willi syndrome. As there are overlapping clinical features between these two syndromes a causal relationship cannot be excluded. However, molecular analyses with 10 probes from this region did not detect any uniparental disomy or deletion, features frequently found in Prader‐Willi syndrome.
Reproductive behaviour following spontaneous loss of a pregnancy after prenatal diagnosis
Authors: Brandenburg Helen , Groenhuijzen Jolanda , Jahoda Milena G. J. , Stijnen Theo , de Ridder Maria A. J. , Sachs Eva S. , Wladimiroff Juriy W.
Published: July 2010

One hundred and fifty‐eight women of advanced maternal age with complete follow up who experienced spontaneous fetal loss after prenatal diagnosis were studied for reproductive behaviour as well as prenatal diagnosis in a subsequent pregnancy. A higher rate of subsequent pregnancies amongst women who experienced an early spontaneous abortion after chorionic villus sampling (CVS) was expected compared with women who lost a pregnancy later during pregnancy after amniocentesis. Of the 92 women who underwent CVS in a previous pregnancy, 57 (62%) became pregnant again. Of the 66 women who underwent amniocentesis in the pregnancy that ended in fetal loss, 34 women (52%) had a subsequent pregnancy. The cumulative incidence of subsequent pregnancies was significantly influenced by maternal age but not by parity or the method of prenatal testing. Most women who decided on a new pregnancy opted for prenatal diagnosis. There was a preference for amniocentesis if the patient had previously undergone CVS. However, the reverse was not the case.
DNA polymorphisms of the apolipoprotein B gene in Chinese coronary artery disease patients
Authors: Saha N. , Tong M. C. , Tay J. S. H. , Jeyaseelan K. , Humphries S. E.
Published: July 2010

Five restriction fragment length polymorphisms (RFLP) of the apo B gene and their association with serum lipids and apolipoprotein levels have been studied in 139 Chinese patients with angiographically confirmed CAD (mean age 56.2 ± 0.8 years) and 154 healthy Chinese subjects (mean age 44.0 ± 1.0 years) of both sexes. The patient group had significantly higher levels of serum total and LDL cholesterol; and apo B (P<0.001) and lower HDL cholesterol and apo A‐I (P<0.001 and <0.01, respectively). The frequencies of the rarer alleles of the ins/del, XbaI and EcoRI (but not the PvuII and MspI) polymorphisms were significantly lower in the Chinese compared to those reported in Caucasians. There was no significant difference in allelic frequencies of the signal peptide region (Ins/Del), XbaI, MspI and EcoRI sites of the apo B gene between the patient and control groups. The frequency of the rarer allele of the PvuII RFLP was significantly lower in the CAD patients (P<0.05) compared to that in the control group (0.05 vs 0.10). None of the DNA polymorphisms was associated with a significant influence on serum lipid and apolipoprotein levels in the patients with coronary artery disease.
Ring chromosome 22 and neurofibromatosis
Authors: Tommerup N. , Warburg M. , Gieselmann V. , Hansen B. R. , Koch J. , Petersen G. B.
Published: July 2010

Variable constitutional mosaicism, mos45,XY,‐22/46,XY,‐22,+mar/46,XY,‐22,+r(22)/47,XY,‐22,+r(22)+mar/47,XY,‐22,+r(22)*2, was found in PHA‐stimulated peripheral blood, in a lymphoblastoid cell line and in cultured skin fibroblasts from a mentally retarded patient with neurofibromatosis. Both the ring chromosome and the small extra marker chromosome stained positively by in situ hybridization with a chromosome 14/22‐specific alphoid repeat probe. DNA dosage analysis showed constitutional loss of one copy of the arylsulfatase A gene (ARSA), consistent with its terminal location on 22q. There was no evidence of constitutional loss of D22S1 or D22S28 which flank the neurofibromatosis type 2 (NF2) locus. Analysis of two DNA samples from a skin neurofibroma indicated retainment of two copies of D22S1, whereas the results were ambiguous with respect to tumor‐specific loss of one copy of D22S28. It is suggested that the development of neurofibromatosis of unclear type in two r(22) carriers might be associated with somatic mutation of the NF2 locus due to instability of the ring chromosome(s), and in analogy, that somatic mutation of either NF1 or NF2 may account for some cases of neurofibromatosis which do not meet the criteria of either NF1 or NF2. The occurrence of seminoma in the proband may be fortuitous, but could also be due to the presence of a seminoma‐associated locus on chromosome 22.
Deletion of 15q12 in Angelman syndrome: report of 3 new cases
Authors: Tonk Vijay , Wyandt Herman E. , Michand Lucille , Milunsky Aubrey
Published: July 2010

Deletion of 15q12 has been reported in patients with Angelman syndrome (AS). We report chromosome studies showing del(15q12) in three new cases, diagnosed as having AS. We were also able to determine, through heteromorphism studies, that the origin of the deleted chromosome in all three probands is maternal. This is a consistent finding in previously reported cases of AS.
Fertility in myotonic dystrophy in Saguenay‐Lac‐St‐Jean: a historical perspective
Authors: Dao To‐Nga , Mathieu Jean , Bouchard Jean‐Pierrs , Braekeleer Marc De
Published: July 2010

Myotonic dystrophy (MD) is an autosomal dominant disorder that has a high prevalence in Saguenay‐Lac‐St‐Jean. A case‐control study, based on a population register, of 373 MD patients who married in this region between 1855 and 1971 was conducted to determine whether their fertility was affected by the disorder. Six demographic parameters, that is the number of children, the age at marriage, the ages at the time of birth of the first and the last child, the interval between the marriage and the birth of the first child, and the interval between consecutive births, were analyzed. The mean number of children born to MD and control individuals was not different (P>0.05). However, MD males had more children than MD females although they have started delaying their marriage since 1921. Fertility fell significantly in both the MD and control groups during the period of observation. This change reflects the decline in fertility of French Canadians in general during this period, but mainly after 1940.
The Dyggve‐Melchior‐Clausen syndrome in Indian siblings
Authors: Winship W. S. , Rubin D. L.
Published: July 2010

The clinical and radiographic features of a brother and sister with the Dyggve‐Melchior‐Clausen syndrome are presented. These features differentiate this syndrome from other bone dysplasias causing short trunk dwarfism. In addition to the vertebral, pelvic and proximal limb defects typical of this syndrome, both these patients have more severe distal limb involvement than has been described previously. Their parents are first cousins and have four other unaffected children, which supports an auto‐somal recessive mode of inheritance for this syndrome. The ancestors of this kindred emigrated to South Africa from India in the 19th century.
Analysis of three glucose transporter genes in a Caucasian population: no associations with non‐insulin‐dependent diabetes and obesity
Authors: Oelbaum R. S.
Published: July 2010

The significance of variation within the genes coding for three glucose transporter proteins in the aetiology of non‐insulin dependent diabetes mellitus was assessed by analysing restriction fragment length polymorphisms in an English Caucasian population. Two polymorphisms at the HepG2/erythrocyte glucose transporter (GLUT1) locus, four at the liver/ pancreatic glucose transporter (GLUT2) locus and one at the muscle/ adipocyte glucose transporter (GLUT4) were analysed in a sample of diabetic and non‐diabetic subjects. No significant differences in the allelic, genotypic or haplotypic frequencies of the polymorphisms at these three loci were observed between the diabetic or non‐diabetic populations. No significant linkage disequilibrium was observed between the two GLUT1 polymorphic sites, whereas the four polymorphic sites at the GLUT2 locus, one of which appears to be due to a 100–200 base pair DNA insertion/deletion, were found to be in significant linkage disequilibrium. In order to study the possible role of glucose transporter gene variants contributing to the development of obesity, the body mass indexes were compared in the different genotypic groups of diabetic and non‐diabetic subjects. No differences in body mass index between genotype groups were found at the p < 0.005 level of significance.
Deletion ΔF508 and clinical expression of cystic fibrosis‐related liver disease
Authors: De Arce M. , O'Brien S. , Hegarty J. , O'Mahoney S. M. , Cashman S. M. , Martinez A. , Delgado M. , FitzGerald M. X.
Published: July 2010

A study of liver function in 108 adult cystic fibrosis patients showed that 20 had established liver disease, and that these had significantly better pulmonary function than the subgroup without liver disease. The relative risk of liver disease for homozygotes vs heterozygotes was 2:1 in our series. Four of the liver patients had a sibling with CF, but three of the sibships were discordant for liver disease. Environmental or genetic factors other than the deletion Delta F508 may influence the development of cystic fibrosis‐related liver disease.
Detection of the Pro664‐Leu mutation in the low‐density lipoprotein receptor and its relation to lipoprotein(a) levels in patients with familial hypercholesterolemia of Dutch ancestry from The Netherlands and Canada
Authors: Defesche J. C. , van de Ree M. A. , Kastelein J. J. P. , van Diermen D. E. , Janssens N. W. E. , van Doormaal J. J. , Hayden M. R.
Published: July 2010

From a large cohort of hyperlipidemic patients, who attended the Lipid Research Clinic in Amsterdam, The Netherlands and in Vancouver, Canada, 915 consecutive patients with familial hypercholesterolemia (FH) of Dutch descent, were selected. This group of FH patients was screened for the presence of a cytosine to thymidine nucleotide substitution in exon 14 of the LDL‐receptor gene, in order to determine the frequency of this mutation in patients of Dutch descent and to investigate the relationship between the mutation and the level of lipoprotein(a). The mutation was detected in seven individuals. All patients with this mutation shared the same haplotype, which is suggestive of an ancient mutation. The index patients and a large kindred with this mutation were further analyzed at the biochemical and clinical level. Except for total and LDL‐cholesterol, there was no statistically significant difference in biochemical parameters between family members with and without FH. In contrast to previous reports, there was no difference in plasma levels of lipoprotein(a) between patients with the mutation in exon 14 and unaffected individuals.