bluuebunny/crossref_metadata_2025 huggingface dataset:
Population frequency of apolipoprotein E5 (Glu3→Lys) and E7 (Glu244→Lys, Glu245→Lys) variants in western Japana
Authors: Matsunaga Akira , Sasaki Jun , Moriyama Kengo , Arakawa Fumiko , Takada Yoichi , Nishi Kayo , Hidaka Kazuko , Arakawa Kikuo
Published: July 2010

Apolipoprotein (apo) E modulates the catabolism of chylomicrons and of very low density lipoprotein remnants. It has three major isoforms (apo E2, E3, E4) and some rare variants. To detect the variants of apo E, blood specimens from 1269 Japanese subjects were analyzed using isoelectric focusing with immunoblotting. The E5 and E7 variants were identified by IEF in 2 and 18 subjects, respectively. Both E5 (Glu3→Lys) carriers were confirmed by PCR‐mediated site‐directed mutagenesis, and all E7 (Glu244→Lys, Glu245→Lys) carriers were confirmed by the amplification refractory mutation system. The relative frequencies of the ε5 and ε7 alleles were 0.001 and 0.007, respectively. High concentrations of total cholesterol (>220 mg/dl) were detected in five of the subjects expressing apo E7 and one subject expressing apo E5, and eight subjects heterozygous for apo E7 showed elevated plasma triglyceride concentrations (>150 mg/dl). In 621 healthy subjects, the mean triglyceride concentration in subjects with apo E7/3 appeared to be higher than in those with apo E3/3, but the difference was not statistically significant.
Clinical and molecular analysis of a Japanese boy with Morquio B disease
Authors: Ishii Nozomi , Oohira Takahiko , Oshima Akihiro , Sakuraba Hitoshi , Endo Fumio , Matsuda Ichiro , Sukegawa Kazuko , Orii Tadao , Suzuki Yoshiyuki
Published: July 2010

Morquio B disease was found in a 15‐year‐old Japanese boy who presented with progressive generalized skeletal dysplasia without neurological manifestations. Mild keratan sulfaturia was found, and β‐galactosidase was deficient in fibroblasts. Gene analysis revealed two mutant alleles, 83Tyr→ His (Y83H) and 482Arg→Cys (R482C). The former expressed a low enzyme activity (2–5% of normal), and the latter expressed no detectable enzyme activity.
A rare G6490 → substitution at the last nucleotide of exon 10 of the glucocerebrosidase gene in two unrelated Italian Gaucher patients
Authors: Seri Marco , Filocamo Mirella , Corsolini Fabio , Bembi Bruno , Barbara Cristiana , Gatti Rosanna
Published: July 2010

Mutation screening of the glucocerebrosidase gene by SSCP analysis revealed an abnormal pattern of exon 10 in two unrelated Italian Gaucher patients. Direct sequencing of the mutated samples identified a G6490→ A transition. The same mutation has been described before in a Japanese patient with Gaucher disease type III. The clinical phenotype of our patients was type I in one whose second allele carried the N370S mutation and type II in the other one with a L444P mutation. In this latter the G6490→ A substitution cancels a normal Msp I site, while on the opposite chromosome the T6433→ C mutation (L444P) introduces a new Msp I site. Thus, digestion with Msp I of the amplified exon 10 is a useful method for identifying the two mutations simultaneously.
Clinical phenotype associated with terminal 2q37 deletion
Authors: Conrad Beth , Dewald Gordon , Christensen Eric , Lopez Michaelene , Higgins James , Pierpont Mary Ella
Published: July 2010

Three children with deletions of the terminal portion of the long arm of chomosome 2 [del (2) (q37)] are described and their clinical findings compared to published cases of 2q terminal deletions. Common clinical findings include development delay, macrocephaly, frontal bossing, depressed nasal bridge and cardiac anomaly. Hypotonia and repetitive behavior are also seen during different times of development. The facial characteristics of children with 2q terminal deletions are not uniform, but development delay is a constant finding. Chromosomal analysis of such children using high resolution banding may uncover the diagnosis of a small chromosomal deletion.
Monosomy 21q: two cases of del(21q) and review of the literature
Authors: Huret J.‐L. , Léonard C. , Chery M. , Philippe C. , Schafei‐Benaissa E. , Lefaure G. , Labrune B. , Gilgenkrantz S.
Published: July 2010

We report on two cases of partial monosomy 21 and review cases with a partial or an apparently full monosomy 21. In situ hybridization and/or molecular studies appear to be necessary tools to study imbalance in such a small chromosome and to perform further genotype‐phenotype correlations. The segregation mode in cases with a translocation is adjacent 1, adjacent 2, and 3:1 in about 1/4, 1/4, and 1/2 of the cases, respectively.
Cytogenetic and molecular cytogenetic studies of a case of interstitial deletion of proximal 15q
Authors: Tonk Vijay , Wyandt Herman E. , Osella Peter , Skare James , Wu Bai Lin , Haddad Bassem , Milunsky Aubrey
Published: July 2010

A 4‐month‐old child with multiple anomalies was determined to have an interstitial deletion of chromosome 15, i.e., del(15) (q12q14). The deletion appears not to be a typical deletion of 15q12 such as seen in Angelman and Prader‐Willi syndromes, but appears to be more distal, involving either loss of all of 15q12 and part of 15q14, or part of 15q12 and most of 15q14. In either case, 15q13 is missing. Fluorescent in situ hybridization with probes for 15 centromere (D15Z), pericentromeric satellite sequences (D15Z1), and chromosome 15 painting probes shows the deleted chromosome to involve only 15 and no other acrocentric chromosome. Hybridization with probes for the AS and PWS loci (D15S11 and GABAB3, Oncor) show both sites to be intact in the deleted 15. The case is compared with two other reports with overlapping interstitial deletions of proximal 15q, neither of which shows typical features of Angelman or Prader‐Willi syndromes.
Unexpected familial recurrence of iris coloboma. A delayed mutation mechanism?
Authors: Barros‐Nuñez P. , Medina C. , Mendoza R. , Sanchez‐Corona J. , Garcia‐Cruz D.
Published: July 2010

Typical isolated ocular coloboma is a congenital abnormality caused by a defective closure of the embryonic fissure of the optic cup. Although an irregular autosomal dominant mechanism of inheritance has been proposed, there is some evidence of other modes of transmission and etiologies. This report shows an unexpected recurrence of iris coloboma, occurring in three sibships of the same family, that could be explained by a “delayed mutation” or “premutation” mechanism.
Characterization of a ring chromosome 21 by FISH‐technique
Authors: Conte Robert A. , Luke Sunny , Verma Ram S.
Published: July 2010

Ring chromosomes 21 that contain two copies of the Down syndrome critical region (DCR1), thereby contributing to trisomic dosage, have not been fully characterized by routine cytogenetic methods in the past. We therefore employed the fluorescence in situ hybridization (FISH) technique, using a battery of chromosome 21 probes and conclude that the ring resulted from a centromere to centromere and long arm to long arm fusion that contains alpha‐satellite DNA and two copies of the D21S65 locus, but lacks beta‐satellite DNA and telomeric DNA. Consequently, we suggest that the origin of the ring may be due to the misdivision of the centromere following the duplication of the long arm, forming a monocentric isochromosome followed by breakage in a region distal to the D21S65 locus and proximal to the telomeric sequences followed by reunion of the broken ends resulting in a monocentric ring. Different ring configurations or fragments were not detected, suggesting that the ring chromosome was highly stable. Apparently, the presence of two copies of Down syndrome loci within the ring chromosome, along with one copy on the normal homologue, caused the clinical consequences of Down syndrome.
Late diagnosis of Down syndrome due to incorrect cytogenetic diagnosis and extreme prematurity
Authors: Druce Maralyn , Cohen Ian J. , Naor Norah , Shohat Mordechai
Published: July 2010

A 26‐week gestation, premature neonate who developed a transient myeloproliferative disorder is presented. The morphological features of Down syndrome were not obvious at this gestational age, and the cytogenetic studies gave a misleading normal karyotype after the infant received non‐irradiated blood. The diagnosis of Down syndrome was not made until 27 weeks after delivery. The problem of misleading cytogenetic results is discussed in particular in premature infants receiving transfusions with non‐irradiated blood products. Although the possibility of uniparental diosomy due to loss of one chromosome 21 was not excluded, this seems to be the first report of a false‐normal cytogenetic study after non‐irradiated blood.
A new syndrome with cardiac malformation, cleft lip‐palate, microcephaly and digital anomalies?
Authors: Perçin E. Ferda , Düzcan Füsun , Kafali Gülden , Sezgin Ilhan
Published: July 2010

A family with cardiac malformation, cleft lip‐palate, short stature, microcephaly, distally placed thumbs, short 2nd and 5th fingers, long and broad 1st toes, broad distance between 1st and 2nd toes and mediodorsal curvature of the 4th toes with syndactyly of the 2nd and 3rd toes has been described as having a new syndrome. While some members of the family had full signs of the syndrome, others had similar but fewer and less severe anomalies of the same structures. The presence of common findings in three generations, its variable expressivity and pleiotropism, and the non‐consanguineous history in the parents suggest that the inheritance is autosomal dominant.
Pericentric inversion with a minute deletion of the Y chromosome in a severely oligozoospermic man
Authors: Iwamoto Teruaki , Nakahori Yutaka , Nakagome Yasuo , Yajima Michitaka , Satomi Yoshiaki , Osada Takao
Published: July 2010

An apparent pericentric inversion of the Y chromosome in a severely oligozoospermic infertile patient is described. The karyotype was 46,X,inv (Y) (p11.2 q11.23). DNA analysis, however, revealed a deletion involving nine loci within the most distal part of the euchromatic region of the long arm.
Charcot‐Marie‐Tooth type 1B neuropathy: third mutation of serine 63 codon in the major peripheral myelin glycoprotein P0 gene
Authors: Blanquet‐Grossard Françoise , Pham‐Dinh Danielle , Dautigny André , Latour Philippe , Bonnebouche Christine , Corbillon Emmanuel , Chazot Guy , Vandenberghe Antoon
Published: July 2010

We report studies on two patients (a mother and her daughter) presenting with a Charcot‐Marie‐Tooth type 1 (CMT1) phenotype: low nerve conduction velocities of 13–15 m/s and an early onset at the age of walking. DNA analysis of the gene coding for the major peripheral myelin protein P0 showed a new point mutation in exon 2, which resulted in substitution of a phenylalanine for serine at amino acid position 63 of P0. This is the third mutation reported at this codon, the two previously described leading to CMT1B (serine 63 deletion), or to Dejerine‐Sottas disease (cysteine for serine 63 substitution), suggesting that different phenotypes can result from alteration of a single amino acid, depending on the type of the change involved.
Common genetic variants of lipoprotein lipase that relate to lipid transport in patients with premature coronary artery disease
Authors: Zhang Q. , Cavanna J. , Winkelman B. R. , Shine B. , Gross W. , Marz W. , Galton D. J.
Published: July 2010

Two common coding sequence mutations of lipoprotein lipase (serine447‐ter, producing a carboxy terminal truncation; and asp9‐asn variants) were studied in 329 Caucasian subjects, of whom 243 had angiographic features of premature atheroscelerosis (220 with coronary artery disease; 23 with coronary and peripheral artery disease). As expected, the mean levels of cholesterol, triglycperides, LDL‐cholesterol, ApoB and Lp(a) were significantly higher in the arterial disease group than in the controls. HDL levels were lower in the patient group. With regard to the common mutations, plasma triglycerides and VLDL‐triglycerides were lower in subjects possessing the Serine447‐Ter mutation (p=0.06 and <0.05, respectively). When the lipid distributions were analysed by tertiles, the Ser447‐Ter mutation was significantly less frequent in the highest tertiles for triglycerides (p<0.02), and VLDL (p<0.04). The Asp9‐Asn substitution was significantly more frequent in the lowest tertiles for ApoAI (p=0.05). Case‐control analyses of genotypic distributions between the two groups with or without arterial disease did not show any significant differences. The possible functional effects of these common mutants of lipoprotein lipase are discussed.
Molecular genetic analysis of exons 1 to 6 of the APC gene in non‐polyposis familial colorectal cancer
Authors: Joyce Johanna A. , Froggatt Nicola J. , Davies Rhodri , Evans D. Gareth R. , Trembath Richard , Barton David E. , Maher Eamonn R.
Published: July 2010

Familial adenomatous polyposis coli is caused by constitutional mutations in the APC gene. The hallmark of familial adenomatous polyposis coli is the presence of numerous (>100) colorectal polyps, but mutations in the 5′ end of the APC gene have been associated with familial colorectal cancer without florid polyposis. Although familial adenomatous polyposis coli accounts for only a minority of familial colorectal cancer cases, we hypothesised that APC mutations which were not associated with florid polyposis might make a significant contribution to nonpolyposis familial colorectal cancer. To investigate this possibility, we analysed 40 unrelated patients with familial colorectal cancer without classical familial adenomatous polyposis coli for mutations in exons 1 to 6 (codons 1 to 243) of the APC gene. No mutations were detected, but a C→T polymorphism at nucleotide 333 (Arg→Trp at codon 99) was identified. No 5′ APC mutations were detected in two patients with desmoid tumours and a family history of colorectal cancer and polyps. We conclude that mutations in exons 1 to 6 of the APC gene are infrequent in patients with familial colorectal cancer who do not have many colorectal polyps.
Trisomy 3 mosaicism on CVS: case report with literature review and propositions for investigation and counseling
Authors: DeLozier‐Blanchet C. D. , Francipane L. , Morris M. A. , Hoovers J. M. N. , Leschot N. J. , Cox J. N.
Published: July 2010

Chorionic villus sampling performed for advanced maternal age revealed trisomy 3 in 20% of mitoses studied after a semi‐direct chromosomal harvest. Amniocytes and cord blood showed a non‐mosaic 46,XY karyotype. The birthweight of the normal newborn was at the tenth percentile. Analysis of term placenta by cytogenetics and by fluorescent in situ hybridization (FISH) confirmed the presence of the trisomy 3 in 20% and 12%, respectively, of cells from two peripheral placental biopsies. Placental histology was heterogeneous, some portions showing immature, edematous and undervascularized villi. DNA analysis confirmed the biparental origin of the chromosomes 3 in the child, whose development is normal at 36 months.
Trisomy 1 mosaicism only detected on a direct chromosome preparation in a neonate
Authors: Howard P. J. , Cramp C. E. , Fryer A. E.
Published: July 2010

A patient is described with trisomy 1 mosaicism which was discovered on 24‐h culture of a neonatal blood sample, but was not detectable on subsequent 48‐ and 72‐h cultures. This result complements other recent reports and has important implications for the detection of mosaicism in neonates.
Familial transmission of a duplication‐deficiency X chromosome associated with partial Turner syndrome
Authors: Aller V. , Gargallo M. , Abrisqueta J. A.
Published: July 2010

A rearranged X chromosome Xqter→q13::Xp11.4→qter was found in a mother and her two daughters, who were affected with short stature, cubitus valgus and hypothyroidism. The mother's menstrual cycles were normal until the age of premenopause. Similar previously reported cases are considered in an attempt to explain the possible origin of this X recombinant, fertility and clinical traits.
De novo balanced 5;21 translocation in a child with acrobrachycephaly, ventriculomegaly, pulmonary stenosis, ectopic anus and mental retardation
Authors: Hordnes Knut , Engebretsen Lars Fredrik , Knudtzon Jørgen
Published: July 2010

An apparently balanced de novo reciprocal translocation t(5;21) (q13;q22) was demonstrated in a girl with acrobrachycephaly, ventriculomegaly, pulmonary stenosis and anal malformation. The possible relationships between her karyotype and malformations are discussed.
Cockayne syndrome type III with high intelligence
Authors: Czeizel Andrew E. , Marchalkó Márta
Published: July 2010

A female patient with some characteristic symptoms of Cockayne syndrome is presented; however, she has high intelligence, and is not a dwarf but is cachectic (30 kg): No characteristic neurological features were seen, and her menstrual cycle is regular. Her disease was thus considered to be Cockayne syndrome type III.
Evidence for genetic influences on smoking in adult women twins
Authors: Edwards Karen L. , Austin Melissa A. , Jarvik Gail Pairitz
Published: July 2010

The purpose of the present study was to examine genetic influences on smoking behavior in women twins, and to compare the results before and after adjusting for environmental covariates. Subjects were participants in the Kaiser Permanente Women Twins Study in Oakland, California. Exam 1 (1978–1979) included 434 pairs of women, and exam 2 (1989–1990) included 352 pairs of women. For comparison with a previous study in male twins, pairwise concordance ratios (OCR) for smoking status between monozygotic (MZ) and dizygotic (DZ) twins were calculated. Multivariate logistic regression analysis was also used to assess the association of smoking behaviors between co‐twins, adjusting for age, education, and frequency of contact. At exam 1, OCR's were consistent with previous results in male twins, and supported genetic influences on smoking initiation (OCR = 1.6; 95% Confidence Interval (95% CI)=1.0, 2.3) and maintenance (OCR=1.8; 95% CI=1.3, 2.4). In contrast to the males, however, no clear evidence for genetic influences on smoking intensity or never smoking were present. The adjusted logistic regression models appeared to confirm the findings from the pairwise comparisons. The results were similar for exam 2. These results are consistent with modest genetic influences on smoking initiation and maintenance. Differences between these results and those for the male twins suggest possible genetic‐environmental interactions.
Familial intestinal polyatresia syndrome
Authors: Güngör Neslihan , Balci Sevim , Tanyel F. Cahit , Göğüş Safiye
Published: July 2010

Familial multiple‐level intestinal atresia is a rare syndrome with autosomal recessive inheritance. Only a few well‐documented families have been reported in the medical literature. In this article two new cases from a consanguineous couple are presented. These are the first reported cases of Familial Intestinal Polyatresia Syndrome from Turkey. The importance of this report is that the recognition of multiple intestinal atresias as an invariably fatal syndrome will be helpful for genetic counselling and attempts at early prenatal diagnosis for successive pregnancies in these couples.
A small supernumerary marker chromosome X identified by in situ hybridization
Authors: Silahtaroglu Asli N. , Hacihanefioglu Seniha , Yilmaz Sükriye , Tarkan Yelda , Cenani Asim , Tümer Zeynep
Published: July 2010

Cytogenetic analysis of a girl with moderate mental retardation and dysmorphic features revealed a 46,XX/47,XX,+mar karyotype. Fluorescence in situ hybridization using chromosome specific alpha satellite probes showed that the supernumerary marker originated from the X chromosome. To our knowledge, this is the first reported case of a female patient mosaic for a supernumerary small marker chromosome derived from X, and hence mosaic for trisomy of the pericentric region of the X chromosome.
Deciduous teeth in tuberous sclerosis
Authors: Russell Bjørn G. , Russell Michael B. , Praetorius Finn , Russell Charlotte A.
Published: July 2010

Shed deciduous teeth from patients with tuberous sclerosis, cerebral palsy, Down syndrome, phenylketonuria and healthy persons were examined with a surface microscope. We found enamel pits in all 87 deciduous teeth from the 20 patients with tuberous sclerosis, but in none of the 253 deciduous teeth from 142 controls constituting patients with cerebral palsy, phenylketonuria and Down syndrome as well as healthy persons. Enamel pits always occurred in the facial surface of the central incisor, lateral incisor and canine, while the number of enamel pits in the other surfaces of the deciduous teeth varied from none to nine. Ground sections examined microscopically revealed an undisturbed pattern of incremental lines (Retzius striae) surrounding the pits. In five dental sacs from patients with tuberous sclerosis, microscopic examination showed that the inner surface of the operculum was remarkably more irregular than in control patients.
Parental origin and mechanisms of formation of three eases of 12p tetrasomy
Authors: Turleau Catherine , Simon‐Bouy Brigitte , Austruy Estelle , Grisard Marie‐Claude , Lemaire Françoise , Molina‐Gomes Denise , Siffroi Jean‐Pierre , Boué Joëlle
Published: July 2010

Pallister‐Killian syndrome is a clinically recognizable syndrome characterized by tissue‐limited mosaicism for an extra 12p isochromosome. Very little is known about the underlying mechanism of this rare rearrangement. Microsatellite markers were studied from three fetuses with Pallister‐Killian syndrome and their parents to determine the parent of origin and the cell division yielding the additional isochromosome. In two cases the isochromosome contained the same allele(s) as a normal transmitted chromosome 12, one paternal and one maternal in origin. A third case showed inheritance of two different maternal alleles, indicating that at least one meiotic error was involved in the ultimate formation of the extra isochromosome.
A three‐allelic polymorphic system in exon 12 of the LDL receptor gene is highly informative for segregation analysis of familial hypercholesterolemia in the Spanish population
Authors: Puig Oscar , Chaves F. Javier , García‐Sogo Magdalena , Real José , Gil José V. , Armengod M. Eugenia
Published: July 2010

We have screened exon 12 of the low density lipoprotein (LDL) receptor gene from 46 familial hypercholesterolemia (FH) heterozygotes and 64 normolipidemic controls for two polymorphisms, Hindi, which is caused by a T to C substitution at base 1773, and a C to T transition at base 1725, by using single strand conformation polymorphism (SSCP) analysis. Our results indicate that polymorphism at base 1725, previously reported as very rare from a Japanese sample, is quite frequent in the Spanish population and that it is closely linked to the presence of the Hindi site (HincII+). Thus, both polymorphisms constitute a system of three alleles, typed HincII‐C1725, HincII+C1725, and HincII+T1725, whose frequencies in the FH sample were 0.489,0.347, and 0.164, respectively. No significant differences were found in the allele frequencies between the FH and control samples. This three‐allelic polymorphic system provides a higher information content (PIC value) than the Hindi RFLP alone (0.537 versus 0.373, respectively); therefore, it is an extremely useful marker for linkage analysis of FH in Caucasian populations.
Multifactorial inheritance of non‐syndromic macrocephaly
Authors: Arbour L. , Watters G. V. , Hall J. G. , Fraser F. C.
Published: July 2010

Objective: To reevaluate previous claims that non‐syndromic macrocephaly is usually inherited as an autosomal dominant trait. Design: Head size was measured in the parents and sibs of children with non‐syndromic macrocephaly. Outcome measures: If autosomal dominant inheritance is involved, the frequency distribution should be bimodal. Results: Head circumference of parents and sibs of the macrocephalic probands had a mean significantly greater than the population norm, and a unimodal distribution. Probands with psychomotor impairment had bigger heads, and more had a history of birth difficulty, than did unimpaired probands. Conclusions: The usual genetic basis for non‐syndromic macrocephaly is multifactorial with a polygenic genetic basis, rather than autosomal dominant. Risk of recurrence appears to be much lower than if it would be on the assumption ot autosomal dominant inheritance. Macrocephaly in a parent or sib of an unborn child may present a risk for birth injury to that child. A larger series of patients will be necessary | to resolve this question.
Medical Ethics:The right not to know—worthy of preservation any longer? An ethical perspective
Authors: Austad Torleiv
Published: July 2010

A presumed right not to know has been claimed in several discussions about testing for genetic diseases or genetic risks in families of populations. In this paper, ethical problems arising from the implementation of a possible right not to know are examined.
Poland sequence in two siblings suggesting an autosomal inheritance transmission
Authors: Cohen Amnon , Zecca Silvia , Dassori Alessandra , Pelegrini Monica , Parodi Lorenza , Romano Cesare
Published: July 2010

We report on Poland sequence observed in two siblings (a girl and a boy) in the same family. This suggests an inheritance pattern consistent with an autosomal recessive or dominant trait transmission with reduced penetrance.
De novo direct duplication 3 (p25→pter): a previously undescribed chromosomal aberration
Authors: Kotzot Dieter , Kriiger Carsten , Braun‐Quentin Cordula
Published: July 2010

We report on a case of de novo direct duplication for the distal part of chromosome 3p: 46, XY, dir dup (3) (p25→pter). At the age of 4 years and 7 months, the boy presented with moderate growth and mental retardation, muscular hypotonia, hypoplasia of the left kidney, a short neck, and a square‐shaped face characterized by a broad and flat nasal bridge, slight epicanthus, and full cheeks. So far, only a few cases with such a small distal 3p duplication have been described, and none of them has a de novo direct duplication for this region. In our patient, dysmorphic signs are less impressive, and developmental delay is relatively moderate.
Neuroradiology and clinical aspects of Usher syndrome
Authors: Tamayo Marta L. , Maldonado Cesar , Plaza Silvia L. , Alvira Gustavo M. , Tamayo Gustavo E. , Zambrano Marta , Frias Jaime L. , Bernal Jaime E.
Published: July 2010

We describe the neurological evaluation and MRI analysis of 30 patients, belonging to 16 families with Usher syndrome (US) type I and type II (US1 and US2). In addition to the classic visual and audiological abnormalities seen in these patients, we observed abnormal gait in 88.9% of US1 and in 66.7% of US2 patients and abnormal coordination in 33.4% of US1, and in 58.3% of US2. Borderline mental retardation, depression or bipolar affective disorder were observed in 16.7% of US1 and 33.3% of US2 patients. MRI analysis showed cerebellar abnormalities in 50% of US 1 and 75% of US2 patients, but no clear correlation was observed between structural abnormalities and clinical findings. A pattern for the MRI classification of US patients is suggested.
Glycerol kinase deficiency in two brothers with and without clinical manifestations
Authors: Blomquist Hans K:son , Dahl Niklas , Gustafsson Lars , Heilerud Christina , Holme Elisabeth , Holmgren Gösta , Matsson Lars , von Zweigbergk Monika
Published: July 2010

We report two brothers with glycerol kinase deficiency (GKD). The older brother had serious clinical symptoms, mental and growth retardation, abnormal skeleton, spontaneous fractures and premature loss of abnormal teeth. He and his mother had low serum phosphate levels. He had elevated serum and urine glycerol levels and GKD was found in cultured fibroblasts. Prenatal diagnosis was performed in the second pregnancy. Glycerol kinase activity was considered normal in a chorionic villus sample of the foetus. After birth, it was found that the boy had elevated serum and urine glycerol levels. Enzymatic analysis in cultured fibroblasts revealed that this boy also had GKD, in spite of having no expression of the disease. Chromosomal analyses in the parents and both boys were normal. Major rearrangements or deletions were not detected in molecular studies of DNA from the two brothers. The hybridisation pattern was normal and no allelic loss was observed.
Discordant monozygotic twins with the Schimmelpenning‐Feuerstein‐Mims syndrome
Authors: Schworm H.D. , Jedele K. B. , Holinski E. , Hörtnagel K. , Rudolph G. , Boergen K.‐P. , Kampik A. , Meitinger T.
Published: July 2010

The Schimmelpenning‐Feuerstein‐Mims syndrome (SFM), characterized by linear nevus sebaceous and ocular and neurologic abnormalities, is a sporadic condition without known familial cases or etiology. We report the occurrence of SFM in only one of two monozygotic (MZ) twins. After considering a variety of possible causative mechanisms, we suggest that a postzygotic dominant lethal mutation in mosaic form may best explain SFM and the discordancy for SFM in these MZ twins.
Report of a new case of axial mesodermal dysplasia complex
Authors: Bini R. , Danti D. A. , Materassi M. , Pela I.
Published: July 2010

We present a female child with phenotypical and clinical features of the axial mesodermal dysplasia complex. Typical manifestations of both the Goldenhar syndrome and the caudal regression syndrome are present in this complex. Only a few reports have described patients with this pattern of malformations localized in both the cranial and caudal regions. Our case represents a mild form of the complex and may contribute to a better delineation of this condition.
DNA testing in familial hypertrophic cardiomyopathy: clinical and laboratory implications
Authors: Smart R.V. , Yu B. , Le H. , French J. A. , Richmond D. R. , Jeremy R. W. , Semsarian C. , Cheung L. , Ross D. A. , Trent R. J.
Published: July 2010

Counselling and clinical assessment in familial hypertrophic cardiomyopathy (FHC) is difficult, particularly in the young, since echocardiographic and ECG changes may not be diagnostic and clinical severity can vary. From 1990, when the β‐cardiac myosin heavy chain gene was implicated in the aetiology of FHC, considerable information about the molecular genetics of this disorder has emerged. However, an important question facing health professionals is the practical significance of DNA testing in FHC. The present study describes a DNA‐based approach to screening for five commonly reported mutations involving the‐cardiac myosin heavy chain gene. Approximately 11% of randomly selected families had an abnormality detected.
Nonsyndromic X‐linked mental retardation: review and mapping of MRX29 to Xp21
Authors: Häne B. , Schroer R. J. , Arena J. F. , Lubs H. A. , Schwartz C. E. , Stevenson R. E.
Published: July 2010

The gene responsible for nonsyndromic mental retardation in a family with 7 affected males has been localized to Xp21. The maximal two‐point lod score was 3.31 for tight linkage to marker DXS1202 in Xp21.3‐p22.3 with crossovers between the 3’ portion of the DMD gene (DXS 1234) proximally and locus DXS989 distally. The XLMR gene in this family has been assigned the designation MRX29. The localization overlaps with at least six other MRX entities linked to the distal short arm of the X chromosome.
Association of genetic variation at the β‐fibrinogen gene locus and plasma fibrinogen evels; interaction between allele frequency of the G/A‐455polymorphism, age and smoking
Authors: Thomas A. E. , Green F. R. , Humphries S. E.
Published: July 2010

The β‐fibrinogen G/A‐455 polymorphism genotype along with plasma fibrinogen levels was determined in 482 healthy middle‐aged men, of whom 231 were smokers. Smokers had the highest plasma fibrinogen levels (2.92 g/1), ex‐smokers the next (2.73 g/1), and never‐smokers the lowest levels (2.66 g/1, P < 0.001). Those with one or two A‐455 alleles had significantly higher plasma fibrinogen levels in never‐smokers and ex‐smokers (8.2% and 9.0%, respectively, P < 0.05), and the effect was larger in younger men (45 < 55 years, 11.6%, P = 0.002) than older men (> 65 years, 4.5%, NS), and was not significant in smokers (2.4%, P > 0.05). Allele frequencies were calculated and compared across age groups and between smokers and non‐smokers. The difference in frequency of the A‐455 allele between smokers and non‐smokers varied significantly with age (P < 0.01), with the frequency of the A‐455 allele being significantly lower in smokers than in non‐smokers in subjects aged > 65 years (P < 0.05), but not in younger men. This demonstrates an interaction between age, smoking and allele frequency of the G/A‐455 polymorphism in this population‐based sample.
The Floating‐Harbor syndrome: two affected siblings in a family
Authors: Fryns J. P. , Kleczkowska A. , Timmermans J. , van den Berghe H.
Published: July 2010

In this report we describe two siblings with pre‐and postnatal growth retardation and clinical signs and symptoms most compatible with the diagnosis of Floating‐Harbor syndrome. The oldest sibling, a girl, died in the first year of life from recurrent infections. The younger sibling, a male, is now 16.5 years old and mildly mentally retarded.
Down syndrome associated with a retroperitoneal teratoma and Morgagni hernia
Authors: Quah B. S. , Menon B. S.
Published: July 2010

Down syndrome may be associated with many complications. Among the malignancies associated with Down syndrome, leukaemia is the most common. This is a case report of a patient with Down syndrome associated with both a retroperitoneal teratoma and a Morgagni hernia.
Desbuquois syndrome in an Arab Bedouin family
Authors: Al‐Gazeli L I. , Aziz S. A. A. , Bakalinova D.
Published: July 2010

We report a consanguineous Arab Bedouin family with Desbuquois syndrome, an AR syndrome of midface hypoplasia and joint laxity. We believe this is the first report of this syndrome in Arab Bedouins.
FISH characterization of the Xq21 breakpoint in a translocation carrier with premature ovarian failure
Authors: Riva P. , Magnani I. , Conti A. M. Fuhrmann , Gelli D. , Sala C. , Toniolo D. , Larizza L.
Published: July 2010

A panel of ordered YAC clones, isolated using STSs in the Xq13‐Xq23 region, was used to characterize by Fluorescent In Situ Hybridization (FISH) the Xq21 breakpoint in a t(X;1)(q21;p34) translocation female with premature ovarian failure. The YAC 949E11 was found to span the breakpoint, but also to join the two non‐overlapping YACs 36CB1 and 40AB3, proximal and distal, respectively, to the patient's Xq21 breakpoint.
Craniofacial morphology of the tricho‐dento‐osseous syndrome
Authors: Kula Katherine , Hall Kathie , Hart Thomas , Wright J. Tim
Published: July 2010

Tricho‐dento‐osseous syndrome (TDO) is characterized by abnormal bone, hair, and tooth morphology. However, the reported craniofacial abnormalities are not well characterized. The purpose of this study was to compare the craniofacial parameters of 25 subjects affected with TDO (A) with those of 15 unaffected relatives (U). Standardized lateral cephalograms were traced and digitized. Each subject's data were compared by age and sex to cephalometric standards (Bolton, Behrents); severity was scored by standard deviations from the standard mean, and then grouped into A vs. U. All cephalograms were evaluated for frontal sinuses, mastoid pneumatization, diploe, and bone density, and cranial thickness was measured. Cranial base length (SN; NBa), cranial base angle (BaSN), and mandibular body length (GoPg) were greater in A than in U (p < 0.05). Both groups had longer total and lower facial heights (NMe; ANSMe) compared with normal standards. Frontal sinuses, mastoid pneumatization and diploe were visible less often in A than in U (p < 0.05). Parietal bone and bone at lambda was significantly thicker (p < 0.05) in A than in U. Variability was substantial in many measures in both A and U. The major TDO craniofacial features involve the cranial base, mandibular body length, absence of visible pneumatized mastoids, frontal sinuses and diploe, and thicker cranial bone.
Fanconi anemia complementation group E: clinical and cytogenetic data of the first patient
Authors: Wegner Rolf‐Dieter , Henrichs Ivo , Joenje Hans , Schroeder‐Kurth Traute
Published: July 2010

The clinical and cytogenetic data of the first patient proven to belong to the fifth Fanconi anemia complementation group are described. The Turkish boy presented with psychomotoric retardation, growth retardation, retarded bone age, brachycephaly, hypotelorism. epicanthus, syndactyly, brachydactyly, renal dystopia, and cryptorchism. In addition, an asymmetrical skeletal anomaly was seen with a double distal phalanx of the left thumb and hypoplasia of the right thumb. Typical hematological features of the disorder developed, at the age of 2.5 years, about 1 year after diagnosis. Cytogenetic studies confirmed the clinical diagnosis and revealed a spontaneous chromosomal instability and hypersensitivity to the cross‐linking agents diepoxybutane and Trenimon. The findings in the patient, who is considered to be the standard for the fifth Fanconi anemia complementation group, are compared with data reported for other patients affected with Fanconi anemia.
APC intragenic haplotypes in familial adenomatous polyposis
Authors: Almeida Rosário , Morton Newton , Fidalgo Paulo , Leitāo Nobre , Mira Costa , Rueff José , Monteiro Carolino
Published: July 2010

Genetic epidemiological studies are useful for the knowledge of the association of markers and genes involved in diseases. In the present work, we studied the frequency of four adenomatous polyposis coli intragenic RFLP markers often used in risk evaluation in a population of 10 familial adenomatous polyposis patients from 10 unrelated Portuguese familial adenomatous polyposis families not sharing the same mutation, and in a population of 55 unrelated healthy Portuguese volunteers. We compared the frequency obtained to normal and affected populations and to results already reported in other populations. We observed allelic frequencies for the Portuguese population that agree with the published ones. The intragenic polymorphisms show strong gametic disequilibrium suggesting little recombination between them. We observed haplotype frequencies significantly different in patients and controls. The gametic disequilibrium may be due to a common founder for a proportion of apparently unrelated probands.
Respiratory complications of Ehlers‐Danlos syndrome type IV
Authors: Dowton S. Bruce , Pincott Stuart , Demmer Lurie
Published: July 2010

Pulmonary complications are described in a case of Ehlers‐Danlos syndrome type IV, established by studies of collagen biosynthesis. At age 20.5 years the patient, who had previously suffered a spontaneous colonic perforation, developed intermittent recurrent hemoptysis and had a spontaneous hemopneumothorax. At presentation, imaging studies revealed multiple scattered cavitary lesions in both lungs. On separate occasions large parenchymal cysts ensued and subsequently regressed. Reviews of other reported patients indicate that pulmonary complications do occur in patients with Ehlers‐Danlos syndrome type IV but have not resulted directly in patient mortality.
High incidence of pre‐excitation syndrome in Japanese families with Leber's hereditary optic neuropathy
Authors: Mashima Yukihiko , Kigasawa Kazuteru , Hasegawa Hiroshi , Tani Masato , Oguchi Yoshihisa
Published: July 2010

Cardiac conduction abnormalities have been reported in families with Leber's hereditary optic neuropathy (LHON). The pre‐excitation syndrome, Wolff‐Parkinson‐White syndrome or Lown‐Ganong‐Levine syndrome, is reportedly common in Finns with LHON, being seen in 14 (9%) of the 163 individuals with mitochondrial DNA (mtDNA) mutations. While this syndrome is thought to be rare in other ethnic groups with LHON, the present study of 35 Japanese LHON families confirmed that it is also relatively common among Japanese families, being seen in 5 (8%) of the 63 individuals with mtDNA mutations. It remains to be determined whether the high incidence of the pre‐excitation syndrome in Finnish and Japanese LHON families is due to a particular genetic composition of ethnic groups such as in Finland and in Japan, or only to a reporting bias.
Insertion/deletion polymorphism in the angiotensin‐converting‐enzyme gene and blood pressure during ergometry in normal males
Authors: Friedl Walter , Krempler Franz , Sandhofer Friedrich , Paulweber Bernhard
Published: July 2010

A sample of 66 healthy, unrelated males with normal blood pressure were studied for a possible association between an insertion/deletion polymorphism in the gene coding for the angiotensin converting enzyme and blood pressure response to physical exercise. No association was found between the polymorphism and systolic blood pressure at rest and during stress. Statistically significant associations between the polymorphism and diastolic blood pressure were observed during exercise and poststress. At maximal workload, among homozygotes for the deletion, the mean diastolic blood pressure was 93 (<10) mmHg, among homozygotes for the insertion it was 82 (<8) mmHg and among heterozygotes it was 85 (<10) mmHg. The difference was still statistically significant 3 minutes post‐stress. The angiotensin converting enzyme polymorphism may be a marker for genetically determined differences in the response of the cardiovascular system to physical stress.
Size of 22q deletions in four previously reported patients with conotruncal anomaly face syndrome
Authors: Pierpont John W. , Erickson Robert P. , Thompson Floyd H. , Yang Jin‐Ming
Published: July 2010

Conotruncal anomaly face syndrome (CTAFS) was distinguished from velo‐cardio‐facial syndrome (VCFS) in a bind study, yet shared the finding of 22q11.2 deletions. This work has been extended to show that the 22q11.2 deletions in CTAFS greatly overlap those found in VCFS and many DiGeorge patients. The reason for dissimilar phenotypes with apparently similar 22q11.2 deletions is not yet known.
Mutational screening of APP gene in patients with early‐onset Alzheimer disease utilizing mismatched PCR‐RFLP
Authors: Nishiwaki Yumiko , Kamino Kouzin , Yoshiiwa Aoi , Nagano Keiko , Takeda Masatoshi , Tanabe Hirotaka , Nishimura Tsuyoshi , Kobayashi Toshiko , Yamamoto Hideki , Nonomura Yasuhiro , Yoneda Hiroshi , Sakai Toshiaki , Imagawa Masaki , Miki Tetsuro , Ogihara Toshio
Published: July 2010

To elucidate the frequency of mutations of the β/A4 amyloid protein precursor (APP) gene in early‐onset Alzheimer disease, we designed a mismatched PCR‐RFLP that can identify all kinds of missense mutations at codon 717 in addition to the seven kinds of known mutations at exon 17. When we screened mutations at exon 17 utilizing this method and the double missense mutations at exon 16 of the APP gene by PCR‐RFLP, no cases revealed mutations of the APP gene among 13 familial and 54 sporadic cases, except one family (OS‐1) that had previously been reported and used as a positive control of APP717(Val → Ile). Our results support the hypothesis that mutations in the APP gene are not major causes in early‐onset Alzheimer disease.
Rothmund‐Thomson syndrome in siblings: evidence for acquired in vivo mosaicism
Authors: Lindor Noralane M. , Devries Ellen M. G. , Michels Virginia V. , Schad Christopher R. , Jalal Syed M. , Donovan Kathleen M. , Smithson William A. , Kvols Larry K. , Thibodeau Stephen N. , Dewald Gordon W.
Published: July 2010

Rothmund‐Thomson syndrome (RTS) is an autosomal recessive disorder characterized by skin abnormalities that appear in infancy, skeletal abnormalities, juvenile cataracts and other manifestations of premature aging, and a predisposition to malignancy. The diagnosis is made on clinical grounds as no consistent laboratory test has been identified. Chromosome studies have been reported for only three patients with RTS and in two of these three, trisomy 8 mosaicism was found. We performed a variety of cytogenetic and molecular genetic studies on two siblings with RTS and on their phenotypically normal parents. Two chromosomally abnormal clones involving either trisomy 8 or i(8q) were found in both patients with RTS. These clones were present in vivo, as they were seen in interphase buccal smears and lymphocytes from unstimulated preparations using both conventional cytogenetic studies and fluorescence in situ hybridization (FISH) with a centromere probe for chromosome 8. These results suggest that RTS is associated with in vivo clonal chromosomal rearrangements causing an acquired somatic mosaicism.
Urticaria, arthralgia, and nephropathy without amyloidosis: another variant of the Muckle‐Wells syndrome?
Authors: Throssell D. , Feehally J. , Trembath R. , Walls J.
Published: July 2010

The term Muckle‐Wells syndrome (MWS) describes an autosomal dominant disorder characterised by various combinations of urticaria, sensorineural deafness, amyloidosis, arthralgia and skeletal abnormalities. We describe a family with nephropathy and several symptoms of MWS, but no evidence of deafness or amyloidosis. Since nephropathy without amyloidosis has never been reported in MWS, but deafness is a feature of all reported pedigrees, we conclude that members of this family have a previously unreported inherited predisposition to urticaria, arthralgia and nephropathy which is distinct from the MWS phenotype.
Wolcott‐Rallison syndrome associated with congenital malformations and a mosaic deletion 15q 11–12
Authors: Stewart F.J. , Carson D.J. , Thomas P.S. , Humphreys M. , Thornton C. , Nevin N.C.
Published: July 2010

Wolcott‐Rallison syndrome is a rare autosomal recessive condition first described in 1972. It is characterised by diabetes mellitus which arises in early infancy and multiple epiphyseal dysplasia. We describe an affected girl who had recurrent episodes of hepatic failure for which no obvious cause was found. Post‐mortem examination revealed abnormal pancreatic histology and congenital abnormalities of the central nervous and cardio‐respiratory systems which have not been previously described in this condition. She also demonstrated a deletion at 15q 11–12 in 65% of her cells.
Jumping translocation in a phenotypically normal female
Authors: von Ballestrem C. L. , Boavida M. G. , Zuther C. , Carreiro M. H. , David D. , Gal A. , Schwinger E.
Published: July 2010

“Jumping translocation” (jt) refers to a rare type of chromosome mosaic, in which the same portion of a (donor) chomosome is translocated to different (recipient) chromosome sites. It have mainly been observed in lymphocyte cultures of patients with hematologic malignancies. We report a phenotypically normal female carrying a mosaic of two cell lines with the Xq26‐qter segment translocated to the short arm of chromosomes 15 or 21 in peripheral blood lymphocytes. In skin fibroblasts, only the X/21 translocation was detected. We speculate that recombination between homologous repetitive sequences on non‐homologous human acrocentrics may be the cause of such chromosomal rearrangements.
Benign external hydrocephalus in a boy with autosomal dominant microcephaly
Authors: Akaboshi Izumi , Ikeda Tetsuo , Yoshioka Susumu
Published: July 2010

In a 3‐month‐old boy with microcephaly, magnetic resonance imaging (MRI) revealed accumulation of bifrontal extracerebral fluid. Because of the typical MRI findings and the disappearance of these findings later on, he was diagnosed as a case of benign external hydrocephalus. Both his mother and maternal grandmother had microcephaly, without neurological or dysmorphic manifestations. The pedigree is most consistent with an autosomal dominantly inherited microcephaly. This seems to be the first report of benign external hydrocephalus found in a patient with an autosomal dominant microcephaly.