bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA polymorphisms in linkage disequilibrium at the 3‘ end of the human APO AII gene: relationships with lipids, apolipoproteins and coronary heart disease
Authors: Dupuy‐Gorce A. M. , Desmarais E. , Vigneron S. , Buresi C. , Nicaud V. , Evans A. , Luc G. , Arveiler D. , Marqués‐Vidal P. , Cambien F. , Tiret L. , de Paulet A. Crastes , Roizés G.
Published: July 2010

Two investigations were undertaken to analyze the 3’ region of the apolipoprotein AII (Apo AII) gene in patients with myocardial infarction (MI) and controls. Previous studies have suggested that a MspI polymorphism in this gene may be associated with hypertriglyceridaemia, high levels of HDL cholesterol and Apo AII. To verify this hypothesis, the distribution of MspI genotypes and their possible associations with several plasma lipid variables were studied in 882 subjects (411 cases with MI and 471 controls) from the ECTIM study. There were no differences in genotype and allele frequencies between cases and controls, and no differences in lipid variable levels in controls carrying the less frequent MspI allele vs other controls. Using single‐strand conformation polymorphism (SSCP) analysis, we detected a new polymorphism which caused by a C‐to‐T transition located in the third intron near the splice junction site (acceptor). This polymorphism modifies a Bst Nl restriction site. The ECTIM population was screened for this new marker, and no significant associations with MI and plasma lipid levels were found. Our results suggest that these two variants located in the coding region of the Apo AII gene are unlikely to contribute significantly to the level of plasma lipid variables and the risk of coronary heart disease (CHD) in the European population.
Reduction of CAG expansions in cerebellar cortex and spinal cord of DRPLA
Authors: Aoki M. , Abe K. , Tobita M. , Kameya T. , Watanabe M. , Itoyama Y.
Published: July 2010

Recent studies have identified an unstable expansion of a CAG repeat in a gene located on chromosome 12 as a cause of dentatorubropallidoluysian atrophy (DRPLA). To investigate whether the somatic heterogeneity may relate to the selective neuronal damage caused by the disease, genomic DNA from various tissues of an autopsied patient with DRPLA was examined to compare possible variations of expanded CAG repeats for the disease. Although the size of the expanded CAG repeat from many organs was almost the same as that from peripheral lymphocytes, those from cerebellar cortex and spinal cord were unexpectedly reduced and numbers of peaks within an expanded allele were relatively strict. These results suggest that the CAG repeat is not simply expanded in the genome of the tissues that are most involved in DRPLA, but that another mechanism might be responsible for the specific neuronal death.
Genetic analysis of the glucose‐6‐phosphatase mutation of type la glycogen storage disease in a Chinese family
Authors: Lee Wen‐Jane , Lee Hsien‐Ming , Chi Ching‐Shiang , Shu San‐Ging , Lin Lih‐Yaun , Lin Wen‐Han
Published: July 2010

Type la glycogen storage disease (GSD) is an autosomal recessive metabolic disorder caused by a deficiency in glucose‐6‐phosphatase (GóPase). Polymerase chain reaction (PCR) and nucleotide sequence analysis were used to identify the location and nature of mutations at the GóPase locus in two siblings affected with type la GSD. Both patients are compound heterozygotes with two different single nucleotide substitutions in the two GóPase alleles. A guanine to adenine transition was identified at base position 327 in the exon 2, converting an arginine to a histidine at codon 83. The second substitution was a thymine to adenine transversion at base position 1101 in the exon 5, converting an isoleucine to an asparagine at codon 341. Family study reveals that both parents are heterozygous carriers: the father with a mutant GóPase allele at exon 2, the mother with another mutant GóPase allele at exon 5. This is the first family study in Taiwan on type la GSD identified by molecular analysis. The mutations identified herein are novel substitutions in the GóPase gene. In addition, an adenine to guanine substitution was observed at base position 653 in the exon 5 of GóPase gene in both sibling patients and their parents, as well as in 15 normal Chinese subjects and three normal Caucasian subjects.
Keipert syndrome in two brothers from Turkey
Authors: Balci Sevim , Dagli Safak
Published: July 2010

Two brothers, 17 and 21 years of age, with depressed nasal bridge, prominent frontal bones, hypoplastic maxilla, mild sensorineural hearing loss, broad terminal phalanges and mild pulmonary stenosis are presented. These findings are similar to those of the syndrome described by Keipert et al. in 1973. To the best of our knowledge, this is only the second report of this syndrome.
Life‐threatening cardiac involvement throughout life in a case of Costello syndrome
Authors: Fukao Toshiyuki , Sakai Shinji , Shimozawa Nobuyuki , Kuwahara Takashi , Kano Masatsugu , Goto Emiko , Nakashima Yoshihiro , Katagiri‐Kawade Mayumi , Ichihashi Hiroshi , Masuno Mitsuo , Orii Tadao , Kondo Naomi
Published: July 2010

Costello syndrome is characterized by poor postnatal growth, mental retardation, curly hair, coarse face, loose skin of the hands and feet, and nasal papillomata. Patients with Costello syndrome have a high incidence of cardiac involvement, such as arrhythmias, hypertrophic cardiomyopathy, or congenital anomalies. The importance of cardiac involvement in Costello syndrome has not been strongly emphasized thus far, although arrhythmia and hypertrophic cardiomyopathy are both serious forms of cardiac involvement. We report the case of a Japanese girl with Costello syndrome, who experienced life‐threatening cardiac involvement throughout her life.
Primed IN Situ labelling (PRINS) as a rational procedure for identification of marker chromosomes using a panel of primers differentially tagging the human chromosomes
Authors: Hindkjær J. , Brandt C. A. , Strømkjær H. , Koch J. , Kølvraa S. , Bolund L.
Published: July 2010

PRimed IN Situ labelling (PRINS) is a highly specific and sensitive technique for detecting DNA sequences on human chromosomes in situ. PRINS is currently being introduced for research and routine analysis in clinical and cancer genetics. In this paper, we report a rational PRINS procedure for the rapid identification of marker chromosomes. Using this method it is possible to test a sample from a patient with up to eight different primers simultaneously on one slide. We have synthesized oligonucleotide primers that can differentially tag the human chromosomes, and with the protocol presented in this report we are able to identify the chromosomal origin of a marker chromosome within 2 hours.
A history of miscarriages and mild prognathism as possible mode of presentation of mosaic trisomy 18 in women
Authors: Satge D. , Geneix A. , Goburdhun J. , Lasne‐Desmet P. , Rosenthal C. , Arnaud R. , Malet P.
Published: July 2010

A 22‐year‐old woman seeking medical assistance for hypofertility after two miscarriages had very slight anomalies: mild macrogenia and prognathism, and temporal depilation. Peripheral lymphocytes and fibroblastic karyotypes disclosed the tenth published case of low‐level mosaicism for trisomy 18 with normal intelligence. Subfertility is frequently observed among these patients. As women with this anomaly are at risk of trisomy 18 pregnancies and as five cases have been reported recently, this particular chromosomal anomaly may not be so exceptional and should be investigated in cases of hypofertility.
Partial deletion of the long arm of chromosome 11: ten Japanese children
Authors: Ono Jiro , Hasegawa Tomoko , Sugama Seiichi , Sagehashi Nobuyuki , Hase Yutaka , Oku Kikuko , Endo Yuko , Ohdo Shozo , Ishikiriyama Satoshi , Tsukamoto Hiroko , Okada Shintaro
Published: July 2010

The clinical features of partial deletion 11q were correlated with the size of the deleted region. Ten Japanese children with partial deletion of 11q were investigated. They were divided into three groups. Three patients in the first group had interstitial deletions and preserved subband q24.1. Six patients in the second group demonstrated terminal deletion of 11q including subband q24.1, with typical features of 11q‐syndrome (Jacobsen syndrome). The third group included only one patient, who had terminal deletion of 11q without characteristics of typical 11q—syndrome. Prominent features of patients in the first group included severe mental and motor developmental delay, seizures, cleft lip and palate, and ophthal‐mological findings. Patients in the second group showed mild to moderate developmental delays without deterioration. Abnormalities in neuroimages, high intensity in the cerebral white matter in T2‐weighted magnetic resonance (MR) images, and recurrent infections were not observed after the age of 7 years. The subject in the third group, with the smallest amount of deleted chromosome, did not show developmental delays, suggesting that some unknown genes related to developmental delays may be located adjacent to subband q24.1. Variation in the deleted parts of 11q resulted in different clinical features in each group.
Further evidence of genetic heterogeneity in hereditary hydronephrosis
Authors: McHale Duncan , Porteous Mary E. M. , Wentzel John , Bum John
Published: July 2010

Hereditary hydronephrosis is a rare condition but several families are described in the literature. The inheritance pattern is autosomal dominant (McKusick number 143400) but the exact aetiology of the hydronephrosis is not clear. However, linkage with the HLA region on chromosome six has been shown previously. We report a family not showing linkage to this region, giving further evidence of genetic heterogeneity in this condition.
Congenital scalp defect, distal limb reduction anomalies, right spastic hemiplegia and hypoplasia of the left arteria cerebri media: Further evidence that interruption of early embryonic blood supply may result in Adams‐Oliver (plus) syndrome
Authors: Fryns J. P. , Legius E. , Demaerel Ph. , van den Berghe H.
Published: July 2010

In this report we describe a male patient with the interesting combination of a large congenital scalp defect, distal limb reduction anomalies, right spastic hemiplegia and hypoplasia of the left arteria cerebri media. Follow‐up data from birth up to the age of 18 years revealed positive evolution with low to normal intelligence. The findings in the present patient, i.e. an Adams‐Oliver syndrome associated with a severe neurological deficit, are best explained as resulting from interruption of the early embryonic blood supply.
Unusual segregation of t(11;22) resulting from crossing‐over followed by 3:1 disjunction at meiosis I
Authors: Petković Iskra , de Capoa Adriana , Giancotti Paola , Barišić Ingeborg
Published: July 2010

Reciprocal translocation t(11;22)(q23;q11) is of particular interest because the unbalanced offspring of the translocation carriers usually present with a supernumerary derivative chromosome 22. This common unbalanced karyotype is the result of 3:1 chromosome segregation during meiosis. We report the third case of a rare segregation pattern of a paternal 11; 22 translocation. The proband's karyotype revealed the presence of a der(11) and two copies of a der(22), i.e. 47, XX, t(11; 22)(q23;q11), +der(22) t(11;22)pat. The karyotype is the result of paternal 3:1 segregation after crossing‐over involving the derived and the normal chromosome 22, as revealed by chromosome polymorphism analysis. Contrary to the preferential maternal transmission of this common unbalanced translocation, the data from the literature, including our case, may suggest preferential paternal transmission of this rare type of unbalanced translocation.
A G‐1‐to‐A acceptor splice site LDLR mutant allele leads to reduced relative transcript levels in patients with heterozygous familial hypercholesterolemia
Authors: Jensen H. K. , Jensen L. G. , Hansen P. S. , Bolund L. , Færgeman D. , Gregersen N.
Published: July 2010

A plethora of different mutations in the gene for the low density receptor (LDLR) are responsible for the autosomal dominant inherited disorder familial hypercholesterolemia (FH). However, only a few splice site mutations have been identified in this gene. We here report a defect presumably affecting the splicing of precursor mRNA, resulting from a novel mutation, a G to A transition at the terminal nucleotide of intron 12, of the LDLR gene detected in three unrelated families with heterozygous FH. This mutation markedly reduced the steady‐state transcript level of the mutant LDLR allele as compared to the corresponding normal LDLR allele in heterozygous FH patients as measured by a fluorescence based, allele‐specific quantitation technique. In the FH families, the acceptor splice site mutation cosegregates with hypercholesterolemia, and it is associated with onset of ischemic heart disease in the fifth and sixth decade of life.
De novo 46,XX, dir dup (11)(q13.3→q14.2) in a patient with mental retardation, congenital cardiopathy and thrombopenia
Authors: Legius E. , Wlodarska I. , Selleri L. , Evans G. A. , Wu R. , Smet G. , Fryns J. P.
Published: July 2010

A 31‐year‐old female is reported with mild to moderate mental retardation, facial dysmorphy, congenital cardiopathy, and mild thrombocytopenia as the most important clinical findings. Chromosome analysis in lymphocytes showed a de novo dir dup (11)(q13.3→14.2), by both G‐banding and FISH techniques. Previously reported constitutional duplications of 11q are mostly the result of unbalanced translocations involving chromosome 11q, and are associated with a partial monosomy or trisomy of the translocation partner chromosome. In case of an unbalanced translocation it is not clear which clinical findings result from the chromosome 11 duplication and which result from the abnormality on the translocation partner chromosome. This is the first report on a constitutional duplication of chromosome region 11q13.3→14.2 without involvement of other chromosomes.
A case report: corpus callosum dysgenesis, microcephaly, infantile spasm, cleft lip‐palate, exophthalmos and psychomotor retardation
Authors: Tütüncüoglu S. , Özkinay F. , Genel F. , Uran N. , Özgür T.
Published: July 2010

In this report, a case with corpus callosum dysgenesis, infantile spasm, microcephaly, psychomotor retardation, exophthalmos, cleft lip‐palate and abnormal EEG findings is presented. His parents are first‐degree relatives. We could not fully match the findings of our patient with the criteria of any syndrome published to date.
The CF carrier status is not associated with a diminished self‐concept or increased anxiety: results of psychometric testing after at least 1 year
Authors: Denayer Lieve , Welkenhuysen Myriam , Evers‐Kiebooms Gerry , Cassiman Jean‐Jacques , Van den Berghe Herman
Published: July 2010

To evaluate whether the CF carrier status has any lasting effect on anxiety and on self‐concept at least 1 year after the disclosure of the test result, an in‐depth interview and additional psychological tests were administered in a group of adults who participated in a previous study which suggested a slight stigmatizing effect of the CF carrier status. Besides carrier status, the role of a second factor — degree of relationship — was investigated. Analysis of Variance (MANOVA or ANOVA) revealed no effect on state and trait anxiety (STAI) and almost no effect on the six subscales of the Tennessee Self‐Concept Scale. The absence of a lasting negative effect of the CF carrier status on anxiety and self‐concept is a very important finding. Nevertheless, an intriguing significant interaction effect was found: the group of sibs carrying the CF gene felt less integrated in the family than the group of non‐carrier sibs. This effect of carrier status was not found in the more distant relatives. It is important to pay sufficient attention to this problem during genetic counseling when brothers or sisters of a CF patient receive a test result.
Sex reversal in a child with the karyotype 46, XY, dup (1) (p22.3p32.3)
Authors: Wieacker P. , Missbach D. , Jakubiczka S. , Borgmann S. , Albers N.
Published: July 2010

The karyotype 46,XY, dup(l) (p22.3p32.3) was found in a 10‐year‐old patient with sex reversal, mental retardation and multiple dysmorphic features. In other cases with duplication 1p but different breakpoints cryptorchidism and genital ambiguity have been observed suggesting the dosage effect of a locus in 1p involved in sex differentiation
Deletion or triplication of the α3(VI) collagen gene in three patients with 2q37 chromosome aberrations and symptoms of collagen‐related disorders
Authors: Rauch A. , Pfeiffer R. A. , Trautmann U.
Published: July 2010

Two new cases of del(2)(q37.1) and one case of partial trp(2)(q37) are studied by FISH with cosmid probes from the COL6A3 and PAX3 genes mapped in 2q37.3 and 2q36, respectively. While the PAX3 gene dosage appeared unaffected, the COL6A3 gene was found to be deleted and triplicated, respectively. This finding could explain features of connective tissue disorders such as joint laxity and hypotonia or joint stiffness and epiphyseal dysplasia, particularly documented by congenital dislocation of the radial head. Karyotype‐phenotype correlations witii reference to published cases are discussed.
A female with monosomy 18 mosaicism: a previously undescribed chromosome abnormality
Authors: Khalifa Mohamed M. , Yamashiro Hirotaka , Duncan Alessandra M. V. , Hefferon Michael , Martin Aryn E.
Published: July 2010

We report on a patient with monosomy 18 mosaicism, a previously undescribed chromosome abnormality. The phenotype is reminiscent of chromosome 18 ring mosaicism. The reason that the patient survived may be attributed to low level mosaicism for the monosomy.
A new form of skeletal dysplasia with amelogenesis imperfecta and platyspondyly
Authors: Verloes Alain , Jamblin Paul , Koulischer Lucien , Bourguignon Jean‐Pierre
Published: July 2010

We report two patients, born of consanguineous parents, affected by a disorder resulting in mild growth retardation. Hallmarks are amelogenesis imperfecta (absence of the enamel cap) associated with brachyolmia‐like anomalies: platyspondyly with short pedicles, narrow intervertebral and interpedicular distances, rectangular‐shaped vertebrae with posterior scalloping and herniation of the nuclei, and broad femoral necks. Inheritance appears to be autosomal recessive.
Peripheral blood cell counts in infants with Down's syndrome
Authors: Kivivuori S. M. , Rajantie J. , Siimes M. A.
Published: July 2010

The current literature indicates that several abnormalities have been observed in the three hematopoietic cell lines of infants with Down's syndrome. This prospective, longitudinal study was designed to clarify the physiological variation in peripheral blood cell values of children with Down's syndrome by following 25 such infants during their first year of life. Apart from polycythemia in the first week of life, the hemoglobin concentration was, in general, the same as in normal term infants. At 9–12 months of age values for mean corpuscular hemoglobin and mean corpuscular volume tended to be elevated. Serum erythropoietin concentrations were low to normal. White blood cell counts were slightly lower in children with Down's syndrome than in normal children. The study infants had profound thrombocytosis from the age of 6 weeks to the end of follow‐up at 1 year. This study, the first longitudinal follow‐up of such subjects, indicates that infants with Down's syndrome often have evidence of polycythemia soon after birth and red blood cell macrocytosis and thrombocytosis later in infancy. In conclusion, we carried out peripheral blood cell counts in 25 infants with Down's syndrome, but with no actual hematological disturbance, during their first year of life, and compared them with values for normal term infants.
The spectrum of ocular features in the Williams‐Beuren syndrome
Authors: Winter M. , Pankau R. , Amm Marita , Gosch Angela , Wessel A.
Published: July 2010

One hundred and fifty‐two patients with the Williams‐Beuren syndrome were examined to assess the frequency and severity of ophthalmological features associated with the disorder. Eighty‐two (54%) had strabismus, all but three, esotropia. One hundred and seventeen (77%) patients had blue irides, 10 (7%) green, and 25 (16%) brown. One hundred and twelve (74%) showed a typical so‐called stellate iris pattern of the anterior stroma. Whitish anomalies were also detectable in brown irides. Two 9‐year‐old patients and one 46‐year‐old patient had initial cataract. Of all the patients with funduscopy, 22% had retinal vascular tortuosity. One patient had suspected Rieger syndrome. Two patients had ptosis, one with a Marcus‐Gunn phenomenon. No ocular manifestation of hypercalcaemia was noted.
An Iranian‐Armenian LDLR frameshift mutation causing familial hypercholesterolemia
Authors: Jensen H. K. , Jensen L. G. , Hansen P. S. , Faergeman O. , Gregersen N.
Published: July 2010

We used polymerase chain reaction single‐strand conformation polymorphism (PCR‐SSCP) analysis to detect a mutation in the low density lipoprotein receptor (LDLR) gene in a family of Iranian‐Armenian origin. The mutation, designated FH Yrmeih, deletes two nucleotides from exon 10 of the LDLR gene, which causes a translational frameshift, whereby a truncated LDLR protein of the first 471 residues of the LDLR with an additional 41 abnormal residues and a premature stop codon would be created. The deletion was detected in a father and son with clinical features of heterozygous FH. To our knowledge this is the first pathogenetic LDLR mutation identified in FH patients of Iranian‐Armenian ancestry.
Determination of cystic fibrosis carrier frequency for Zuni native Americans of New Mexico
Authors: Kessler D. , Moehlenkamp C. , Kaplan G.
Published: July 2010

The Zuni native Americans of the Southwest have an incidence of cystic fibrosis of approximately one in 333 or seven and one‐half times that found for Caucasians. Earlier studies indicated that dF508 was not among the cystic fibrosis mutations causing this disease. Through a collaborative study the R1162X mutation was found on 12 out of 12 cystic fibrosis chromosomes from six Zuni patients. Because of the relative high incidence of cystic fibrosis, we undertook a study to determine the carrier frequency of the R1162X mutation among randomly sampled individuals. We found the carrier frequency in the general population for the R1162X to be 6.7%, a very significant number when compared with the carrier frequency for all cystic fibrosis mutations in the Caucasian population of approximately 4%.
Mild CF in a ΔF508/R347H compound heterozygote woman: does the manifestation of this genotype differ in the two sexes?
Authors: Kosztolányi György , Malik Naseem , Rutishauser Marcus
Published: July 2010

A woman with unusually mild cystic fibrosis (CF) and normal sweat chloride levels is reported to have ΔF508 deletion on one CF chromosome and the rare mutation R347H on the other, the first known female with this mutation. Of the other eight cases with R347H mutation mentioned in the literature, all five patients whose age and sex were given in the reports were men and had congenital bilateral absence of vas deferens (CBAVD). Considering these data, it is not unrealistic to assume that R347H associates more frequently than other CF mutations with CBAVD, which would mean that the clinical significance of this mutation might differ in males and females.
“Reduction” of CGG trinucleotide expansion from mother to offspring in seven fragile‐X families
Authors: Loesch Danuta Z. , Petrovic Vida , Francis David I. , Oertel Ralph , Slater Howard
Published: July 2010

Apparent reduction in the size of the CGG repeat is reported from seven fragile‐X mothers to nine offspring in seven extended families. The overall frequency of the reduction amongst 121 fragile‐X mother‐fragile‐X child transmissions was 7.4%, compared with an 18% reduction in fragile‐X father‐fragile‐X daughter transmissions, but ascertainment bias may account for some underestimation of the frequency of reductions, especially between mothers and their offspring. In one mother‐son transmission, a premutation present in the son (with a full mutation present in the mother) was unmethylated. This may be the result of either demethylation with reduction, or undetected mosaicism in the mother. There was no obvious increase in the level of intellectual performance in female offspring who received a reduced fragment from their mothers. Several mechanisms leading to apparent reduction, such as germline mosaicism, deletion or replication slippage, should be considered.
Interaction of the cholesteryl ester transfer protein I405V polymorphism with alcohol consumption in smoking and non‐smoking healthy men, and the effect on plasma HDL cholesterol and apoAI concentration
Authors: Gudnason V. , Thormar K. , Humphries S. E.
Published: July 2010

Three hundred and sixteen healthy Icelandic men and women were examined for the effect of the cholesteryl ester transfer protein (CETP) I405V polymorphism on plasma triglycerides, HDL cholesterol (HDLC) and apoAI concentration. Genotyping was performed using an allele specific oligomelting assay and the frequency of the V allele was 0.31 (95 CI for men 0.23–0.33 and for women 0.29–0.39). In women no significant difference was associated with the V405 genotype for any plasma lipid trait. However, men who were homozygous for the V405 allele had 9% higher apoAI and 14% higher HDLC levels (p < 0.05) than those homozygous for the common 1405 allele. The genotype effect was seen only in the non‐smokers (p = 0.07 and <0.05, respectively), and in those consuming alcohol (p < 0.05 for both). Analysis of interaction between the environmental, life‐style factors and genotype in men for the traits of HDLC and apoAI showed statistically significant interaction of the genotype only with alcohol consumption. The non‐smoking men who reported alcohol consumption and who were homozygous for the CETP V405 allele had 16% higher plasma apoAI concentration than those who carried the 1405 allele, and up to 20% higher apoAI level than smokers. On the basis of prospective studies carried out on the Icelandic population, non‐smoking, alcohol‐consuming men who are homozygous for the V405 allele could have from 32% to 40% lower risk of having a heart attack.
Association analysis of CA repeat polymorphism of the endothelial nitric oxide synthase gene with essential hypertension in Japanese
Authors: Nakayama T. , Soma M. , Takahashi Y. , Izumi Y. , Kanmatsuse K. , Esumi M.
Published: July 2010

The nitric oxide synthase (NOS) gene is thought to be associated with essential hypertension (EH), because NO is implicated in endothelium‐mediated vasodilation. We investigated the possible association between the alleles of simple tandem repeat DNA polymorphism of the endothelial constitutive NOS (cNOS) gene and EH in Japanese subjects. In all, 100 patients with EH and 123 subjects with normal blood pressure were studied. Polymerase chain reaction was used to amplify the CA repeat site in the endothelial cNOS gene and alleles based on the CA repeat number were determined. The allele frequencies in the hypertensive group and normotensive group were then compared. Twenty‐three alleles were identified in this study of Japanese subjects. The overall distributions of allele frequencies in the two groups were not significantly different. However, comparing the allele frequencies in the EH group without left ventricular hypertrophy (LVH) and the normotensive group, the overall distributions were significantly different (p = 0.019). The 33‐repeat allele was found more frequently in the EH group without LVH than in the normotensive group (p = 0.000047, Odds ratio = 3.71). In conclusion, the 33‐repeat allele of the endothelial cNOS gene is associated with EH without LVH, and may be a genetic marker of EH in Japanese subjects.
Are common mutations of cystathionine β‐synthase involved in the aetiology of neural tube defects?
Authors: Ramsbottom D. , Scott J.M. , Molloy A. , Weir D. G. , Kirke P. N. , Mills J. L. , Gallagher P. M. , Whitehead A. S.
Published: July 2010

Mildly elevated maternal plasma homocysteine (Hcy) levels (hyperhomocysteinemia) have recently been observed in some neural tube defect (NTD) pregnancies. Plasma levels of Hcy are governed by both genetic and nutritional factors and the aetiology of NTDs is also known to have both genetic and nutritional components. We therefore examined the frequency of relatively common mutations in the enzyme cystathionine β‐synthase (CBS), which is one of the main enzymes that controls Hcy levels, in the NTD population. Neither the severely dysfunctional G307S CBS allele nor the recently reported 68 bp insertion/I278T CBS allele was observed at increased frequency in the cases relative to controls. We therefore conclude that loss of function CBS alleles do not account for a significant proportion of NTDs in Ireland.
Mutation of RET codon 768 is associated with the FMTC phenotype
Authors: Boccia Lara M. , Green Jane S. , Joyce Carol , Eng Charts , Taylor Sherryl A. M. , Mulligan Lois M.
Published: July 2010

Multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC) are inherited cancer syndromes resulting from mutations in the RET proto‐oncogene. Missense mutations of five codons in exons 10 and 11 are found in both MEN 2A and FMTC families, while mutations at codon 768 in exon 13 have been identified in three FMTC families. We report here the results of mutation analysis on a large multi‐generation family with multiple cases of medullary thyroid carcinoma (MTC) or C‐cell hyperplasia and two individuals with isolated adrenal medullary hyperplasia. A mutation in exon 13, which alters codon 768 from a GAG (Glu) to a GAC (Asp), was found to segregate with the FMTC phenotype in this family but not with the adrenal medullary hyperplasia. These findings suggest that the codon 768 mutation does not predispose to adrenal medullary hyperplasia, but is an accurate predictor of the MTC phenotype in this family.
Centromeric alphoid DNA heteromorphisms of chromosome 21 revealed by FISH‐technique
Authors: Verma Ram S. , Batish Sat Dev , Gogineni Swarna K. , Kleyman Svetlana M. , Stetka Daniel G.
Published: July 2010

The centromeric heterochromatin of chromosome 21 has been evaluated by the fluorescence in situ hybridization (FISH) technique. It was found that the alphoid DNA sequences of pericentromeric regions of chromosome 21 were highly heteromorphic when a centromeric specific probe was hybridized to these sequences. The variations were so extreme that they could even be arbitrarily classified into at least five sizes by comparison with the length of the short arm (p) of chromosome 18. They are: negative (1); small (2); medium (3); large (4); and very large (5). We used 15 normal cases and 12 individuals with trisomy 21 (Down syndrome), and the incidences for these five classes were 3.0%, 22.7%, 59.2%), 13.6% and 1.5%, respectively. At least 3% of the chromosomes no. 21 did not show any trace of hybridization signals, which apparently escape detection at interphase level as well. Although, the variations observed in the present study are continuous, the proposed classification may yield some implications for future investigations.
Congenital cutis laxa and lysyl oxidase deficiency
Authors: Khakoo Abbas , Thomas Roswyn , Trompeter Richard , Duffy Patrick , Price Robert , Pope F. Michael
Published: July 2010

We report two phenotypically similar patients with primary cutis laxa associated with deficiency of lysyl oxidase, an extracellular copper enzyme the gene for which is located on chromosome 5. Previous reports of this condition have had characteristic occipital projections, abnormality of copper metabolism and X‐linked inheritance. The two reported patients have no occipital projections, normal copper metabolism, Wormian bones, and a pattern of inheritance consistent with the autosomal recessive inheritance of the lysyl oxidase gene.
Prenatal diagnosis of a de novo trisomy 6q22.2→6qter and monosomy lpter→1p36.3. Case report with a 2‐year follow‐up and a brief review of other prenatal cases of partial trisomy 6q
Authors: Kulharya Anita S. , Carlin Mary E. , Stettler William A. , Huslig Martine , Kukolich Mary K. , Garcia‐Heras Jaime
Published: July 2010

We report a de novo trisomy 6q22.2→6qter and monosomy lpter→1p36.3 identified in amniocytes by GTG banding and FISH. While ultrasonography demonstrated malformations that did not suggest a specific chromosomal syndrome, a male infant with features consistent with trisomy 6q was born. He was followed up until 23 months, when he died after cardiac surgery. The only two other prenatal cases of trisomy 6q were compared with our patient. A literature review showed that trisomy 6q has not been reported in association with the anomalies seen by ultrasound in this case.
A new case of oculocerebral hypopigmentation syndrome (Cross syndrome) with additional findings
Authors: Tezcan I. , Demir E. , Aşan E. , Kale G. , Müftüoǧlu S. F. , Kotiloglu E.
Published: July 2010

Cross syndrome is a rare syndrome characterized by ocular and cutaneous hypopigmentation and neurological manifestations. A few reports have been published since 1967. In this report, we present a new case of Cross syndrome with additional findings such as urinary tract abnormality, bilateral inguinal hernia, focal interventricular septal hypertrophy of the heart and vacuolization of myeloid series cells and distinct ultrastructural features of the skin.
Möbius‐like syndrome associated with a 1;2 chromosome translocation
Authors: Nishikawa Miki , Ichiyama Takashi , Hayashi Takashi , Furukawa Susumu
Published: July 2010

We report here a rare case of Möbius‐like syndrome associated with a 1;2 chromosome reciprocal translocation (46, XY, t(1;2)(p22.3;q21.1)). The patient had facial diplegia, ptosis, anteverted nostrils, malformed and low‐set ears, and slight developmental delay. Since a microdeletion could be present at the breakpoint in a reciprocal translocation, it is possible that the gene responsible for Möbius syndrome is located in this region of chromosome 1.
Detection of SRY in 45, X/47, XYY mosaicism leading to phenotypic female
Authors: Imai Atsushi , Horibe Shinji , Fuseya Tatsuo , Takagi Hiroshi , Takagi Atsushi , Tamaya Teruhiko
Published: July 2010

SRY on the Y chromosome initiates male sex determination. We tested a phenotypic female with sex chromosome mosaicism, X/XYY, for SRY expression. SRY was determined by polymerase chain reaction (PCR) amplification in genomic DNA from a female patient with a sex chromosome mosaic complement, 45, X/47, XYY, followed by sequencing analyses. The patient yielded the PCR product with predicted size and homology to the consensus sequence of SRY. The demonstration of SRY provides evidence that the female phenotype in the presence of sex chromosome mosaicism, X/XYY, may result from alterations in another part of the sex‐determining pathway or downstream from SRY.
Two novel mutations in a Canadian family with aspartylglucosaminuria and early outcome post bone marrow transplantation
Authors: Laitinen Arja , Hietala Marja , Haworth James C. , Schroeder Marlis L , Seargeant Lome E. , Greenberg Cheryl R. , Aula Pertti
Published: July 2010

Aspartylglucosaminuria (AGU) is a lysosomal storage disease caused by deficiency of aspartylglucosaminidase. The disease is overrepresented in the Finnish population, in which one missense mutation (Cys163Ser) is responsible for 98% of the disease alkies. The few non‐Finnish cases of AGU which have been analyzed at molecular level have revealed a spectrum of different mutations. Here, we report two new missense mutations causing AGU in two Canadian siblings. The patients were compound heterozygotes with a G299→ A transition causing a Gly100→ Gin substitution and a T404→ C transition resulting in a Phe135→ Ser change in the cDNA coding for aspartylglucosaminidase. The younger patient recently underwent bone marrow transplantation.
Evaluation of an aspartame loading test for the detection of heterozygotes for classical phenylketonuria
Authors: Silva L C. S. , Pires R. F. , Coelho J. C. , Jardim L B. , Giugliani R.
Published: July 2010

Classical phenylketonuria (PKU) is an inborn error of metabolism of autosomal recessive inheritance characterized by the accumulation of phenylalanine (Phe) in tissues due to Phe‐4‐hydroxylase deficiency. Several methods have been developed for the detection of PKU heterozygotes based on the determination of plasma Phe and tyrosine (Tyr) levels, on the analysis of the Phe/Tyr and Phe2/Tyr ratios and on the use of discriminant functions. The objective of the present study was to test the value of loading with aspartame (a sweetener consisting of Phe, aspartate and methanol) for the identification of PKU carriers. The study was conducted on 22 obligate heterozygotes and 27 controls. Two blood samples were collected (under fasting conditions and 30 min after the loading) for fluorometric determination of Phe and Tyr. Phe, Phe/Tyr and Phe2/Tyr values were higher in heterozygotes, whereas Tyr was higher in controls in both situations investigated. Linear discriminant function was considered to be the best parameter for differentiation of the individuals in the two groups. Under the conditions employed in the present study, aspartame loading did not show any advantages in discriminating between PKU carriers and normal individuals when compared to the same analysis performed under fasting conditions.
Submicroscopic deletion in chromosome 22q11 in trizygous triplet siblings and their father Clinical variability of 22q11 deletion
Authors: Devriendt K. , Hoestenberghe R. Van , Hole C. Van , Devlieger H. , Gewillig M. , Moerman Ph. , Van den Berghe H. , Fryns J. P.
Published: July 2010

A submicroscopic deletion of chromosome 22q11 was demonstrated in three triplets and in their father. Two children had the typical DiGeorge sequence with at least three of the four cardinal features: conotruncal heart disease, hypoplastic thymus and typical facial features. Hypoparathyroidism was present in one of them. The third child had features of both DiGeorge and velo‐cardio‐facial syndrome (VCFS). The father presented with features compatible with VCFS. This observation further illustrates the wide variability in expression of a submicroscopic deletion of 22q11, even within one family.
Reciprocal translocation 4; 11 with both adjacent‐1 segregants viable within a family
Authors: Rogers Jill Cellars , Harris David J. , Pasztor Linda M.
Published: July 2010

We describe a family carrying a balanced 4; 11 translocation in which both adjacent‐1 segregants are viable. The proband had an unbalanced karyotype: 46,XY,der(11)t(4;11)(q34.3;q23.1)mat. At 8.5 years of age he showed trigonocephaly, hypertelorism, epicanthal folds, down‐slanting palpebral fissures, low‐set ears, anteverted nares, down‐turned carp‐shaped mouth, and bilateral fifth finger clinodactyly. His maternal aunt was also dysmorphic with high‐arched palate, short philtrum and mild developmental delay. Her karyotype was 46,XX,der(4)t(4;11)‐(q34.3;q23.1)pat. Other relatives who likely carried a chromosomally unbalanced segregant were identified from photographs and medical records. We compare the clinical findings in our family with descriptions of other similar karyotypic abnormalities from previous case reports.
Case Report: Prenatal diagnosis of mosaic tetrasomy 21q confirmed by fluorescence in situ hybridization
Authors: Nagarsheth Nimesh P. , Mootabar Hamid
Published: July 2010

We describe the first case of a live‐born neonate with mosaic tetrasomy 21q confirmed by fluorescence in situ hybridization (FISH). A 38‐year‐old Caucasian female presented for amniocentesis for maternal age. Initial chromosome analysis of the amniocytes using GTG‐banding showed a mos47,XY, +?i(12p)/46,XY karyotype. Follow‐up studies with FISH identified the isochromosome as an i(21q); mos47,XY, + i(21q)/46,XY. The patient was delivered at 38 + weeks gestation and umbilical cord blood samples were obtained. Chromosome analysis of 43 cord blood lymphocytes demonstrated a 46.XY karyotype in all cells. However, peripheral lymphocytes taken 1 day after birth showed 1 out of 120 lymphocytes to have an extra chromosome determined to be an i(21q). While initial clinical exam of the neonate revealed similarities to Down syndrome, long‐term follow up of our patient will be required to provide the first definitive description of the mosaic tetrasomy 21 syndrome.
Vocal cord paralysis and cystic kidney disease in Hajdu‐Cheney syndrome
Authors: Fryns Jean‐Pierre , Stinckens Christel , Feenstra Louw
Published: July 2010

In this report we describe the clinical history and symptoms in a 36‐year‐old male with Hajdu‐Cheney syndrome, an autosomal dominant condition with dissolution of the terminal phalanges (acro‐osteolysis), characteristic craniofacial dysmorphism, and musculoskeletal alterations. He was admitted at that age because of progressive respiratory problems, with Cheyne‐Stokes respiration and bilateral vocal cord paralysis. Terminal renal failure with cystic renal disease was diagnosed at the age of 14 years. The findings in the present patient illustrate the risk of progressive neurologic degeneration with involvement of the cranial nerves in patients with Hajdu‐Cheney syndrome. Moreover, we confirm that cystic renal changes are an integral part of Hajdu‐Cheney syndrome, and agree that Hajdu‐Cheney syndrome and Serpentine fibula syndrome are probably variant examples of the same disease.
Marinesco‐Sjögren syndrome associated with acute mveloblastic leukemia
Authors: Fukuda Seiji , Yamada Yukiji , Nishimura Masaaki , Isogai Koji , Terada Tomonori , Iwata Masako , Shimozawa Nobuyuki , Suzuki Yasuyuki , Kondo Naomi
Published: July 2010

Marinesco‐Sjögren syndrome is a rare autosomal recessive disorder characterized by cerebellar atrophy, ataxia, cataracts, short stature and varying degrees of mental retardation. A high incidence of malignant disease associated with this syndrome has not so far been reported. We report the case of a 6‐year‐old girl affected with Marinesco‐Sjögren syndrome, who developed acute myeloblastic leukemia (AML, M2), and whose karyotype was 46,XX,t(8;21),(q22;q22) in bone marrow blasts. This is the first report of Marinesco‐Sjögren syndrome associated with malignant disorders.
MN blood group affects response of serum LDL cholesterol level to a low fat diet
Authors: Birley Andrew J. , MacLennan Robert , Wahlqvist Mark , Gerns Linda , Pangan Theresa , Martin Nicholas G.
Published: July 2010

Previous studies found that MZ twin pairs who are blood group NN have greater intrapair variability in plasma lipid levels than those who are MM or MN. This led to the prediction that the response of plasma lipid levels to a low fat diet would depend on MN blood group, the greatest response being in those who are NN. The present study was based upon 254 patients who took part in the Australian Polyp Prevention Project. This was a 2 × 2 × 2 randomised factorial design based upon the presence or absence of the three factors: a dietary fibre supplement, a beta‐carotene supplement and reduced intake of dietary fat. The lowering of plasma, low density lipoprotein (LDL) cholesterol, in response to a low fat diet was greatest in those who were NN and least in MN heterozygotes. Overall, a reduction in LDL level was observed in the 47% of the APPP population who were on a low fat diet and who were homozygous MM or NN. The result was consistent with a balanced polymorphism at or near the GLYA locus on chromosome 4 that influences the sensitivity of plasma lipid levels to dietary fluctuations in fat intake.
The prevalence of Usher syndrome and other retinal dystrophy‐hearing impairment associations
Authors: Rosenberg Thomas , Haim Marianne , Hauch Anne‐Marie , Parving Agnete
Published: July 2010

The study was undertaken to procure population‐based prevalence data on the various types of Usher syndrome and other retinal dystrophy‐hearing impairment associations. The medical files on 646 patients with a panretinal pigmentary dystrophy aged 20–49 years derived from the Danish Retinitis Pigmentosa (RP) register were scrutinised. The data were supplemented by a prior investigation on hearing ability in a part of the study population. After exclusion of patients with possibly extrinsic causes of hearing impairments, 118 patients, including 89 cases of Usher syndrome were allocated to one of five clinically defined groups. We calculated the following prevalence rates: Usher syndrome type I: 1.5/100000, Usher syndrome type II: 2.2/100000, and Usher syndrome type III: 0.1/100000 corresponding to a 2:3 ratio between Usher syndrome type I and II. The overall prevalence rate of Usher syndrome was estimated to 5/100000 in the Danish population, devoid of genetic isolates. The material comprised 11 cases with retinal dystrophy, hearing impairment, and additional syndromic features. Finally, 18 subjects with various retinal dystrophy‐hearing impairment associations without syndromic features were identified, corresponding to a prevalence rate of 0.8/100000. This group had a significant overrepresentation of X‐linked RP, including two persons harboring a mutation in the retinitis pigmentosa GTP‐ase regulator (RPGR) gene.
Molecular and clinical studies of three cases of female pseudohermaphroditism with caudal dysplasia suggest multiple etiologies
Authors: Erickson Robert P. , Stone J. F. , McNoe Leslie A. , Eccles Michael R.
Published: July 2010

Female pseudohermaphroditism with caudal dysplasia is a clinical entity in which normal‐appearing male genitalia may occur in the apparent absence of testosterone or the sex‐determining gene (SRY). We have extended observations of two previously reported cases, and report a third case, which strongly suggests multiple etiologies. The first case was one of identical twins. The other identical twin did not show female pseudohermaphroditism with caudal dysplasia, but both patients had the rare birth defect of neonatal cataracts. We have explored skewed X‐inactivation as a possible difference between the two twins, with a negative result. The second case had a deletion at 10q25.3→ter. This is near the location of PAX2, and we searched for mutations in PAX2 in both this and the first case, with negative results. Neither patient had a scrotal raphe, suggesting that a failure of division of the cloacal membrane was an important step in their development of female pseudohermaphroditism. The final case is newly described and differed from the above two in the presence of a scrotal raphe and an elevated testosterone level. Although no source for the testosterone was found, this case suggests that the etiology in this patient was different and that the presence of a scrotal raphe can be used to distinguish between at least two etiologies.
Polydactyly and fetal hydantoin syndrome: an additional component of the syndrome?
Authors: Yalçinkaya Cengiz , Tüysüz Beyhan , Somay Göksel , Cenani Asim
Published: July 2010

We report a 3‐year‐old girl with fetal hydantoin syndrome (FHS) whose mother had received phenytoin 600 mg/day throughout gestation. She had growth retardation, mental deficiency, craniofacial dysmorphism and iris colomobata specific to FHS. However, the patient did not have the distal phalangeal hypoplasia which is associated with FHS; instead, she had Polydactyly of the right foot. This seems to be the first FHS case in the literature with Polydactyly.
A patient with Edwards syndrome caused by a rare pseudodicentric chromosome 18 of paternal origin
Authors: Gravholt Claus Højbjerg , Bugge Merete , Strømkjær Helle , Caprani Monna , Henriques Ulrik , Petersen Michael B. , Brandt Carsten A.
Published: July 2010

We present an unusual case of trisomy 18 due to a pseudodicentric chromosome 18 of paternal origin. The karyotype was: 46,XY,—18, + psu dic(18)(qter→cen→p11.31::p11.31→psucen→qter). The origin of the abnormal chromosome was verified by FISH with a painting probe from chromosome 18. Absence of short‐arm telomeres was shown by multicolor FISH, and the results of DNA analysis showed monosomy for loci D18S59 and D18S170 as well as paternal inheritance of the aberrant chromosome. The child's phenotype was characteristic of trisomy 18.