bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontonasal dysplasia, lipoma of the corpus callosum and tetralogy of Fallot
Authors: Meguid Nagawa Abdel
Published: July 2010

Meguid NA. Frontonasal dysplasia, lipoma of the corpus callosum and tetralogy of Fallot.

Clin Genet 1993: 44: 95–97. © Munksgaard, 1993

A 6‐year‐old Egyptian boy with frontonasal dysplasia (FND) and lipoma of the corpus callosum associated with tetralogy of Fallot is reported. The main features were severe hypertelorism, downward slanted palpebral fissures, bilateral epicanthal folds, a grossly deformed nose with notched alae nasi, absent nasal tip and long philtrum. A computerized tomography (CT) scan of the brain showed cerebral atrophy and lipoma of the corpus callosum. While marked neurological symptoms have been reported in cases with lipoma of the corpus callosum in the absence of FND, the present case and previous reports showed minor neurological alterations when lipoma of the corpus callosum was associated with FND. From the findings in this case and previous reports, it is possible to conclude that lipoma of the corpus callosum associated with FND is always located in the anterior part of the corpus callosum. The etiology of FND remains uncertain. While multifactorial inheritance has been proposed, parental consanguinity with young parental age in the present case cannot exclude autosomal recessive inheritance.
Kaufman oculocerebrofacial syndrome: report of two new cases and further delineation
Authors: Figuera L. E. , Garcia‐Cruz D. , Ramirez‐Dueñas M. L. , Rivera‐Rables V. , Cantù J. M.
Published: July 2010

Figuera LE, García‐Cruz D, Ramírez‐Dueñas ML, Rivera‐Robles V, Cantù JM. Kaufman oculocerebrofacial syndrome: report of two new cases and further delineation.

Clin Genet 1993: 44: 98–101. © Munksgaard, 1993

Two unrelated Mexican girls, aged 14 months and 6 years respectively, with Kaufman oculocerebrofacial syndrome, are reported. Both showed psychomotor retardation, microcephaly, blepharophimosis and delayed growth as the main features; the infant also presented preauricular tags and large clitoris. Comparative analysis with previous cases reveals a heterogeneous syndrome in which the micro‐brachycephaly, the mongoloid slanted eyes with different anomalies, the micrognathia and the neonatal respiratory distress are the most typical characteristics of this mental retardation syndrome.
DNA polymorphisms of the apolipoprotein B gene are associated with obesity and serum lipids in healthy Indians in Singapore
Authors: Saha N. , Tay J. S. H. , Heng G. K. , Humphries S. E.
Published: July 2010

Saha N, Tay JSH, Heng CK, Humphries SE. DNA polymorphisms of the apolipoprotein B gene are associated with obesity and serum lipids in healthy Indians in Singapore.

Clin Genet 1993: 44: 113–120. © Munksgaard, 1993

Three DNA polymorphisms (Ins/Del, XbaI and EcoRI) of the apolipoprotein B gene and their influence on body‐mass index, serum lipids and apolipoprotein levels were studied in 181 healthy Indians of both sexes (121 males and 60 females), aged between 17 and 71 years. The frequencies of X+ (XbaI) and Del (Ins/Del) of the signal peptide region in Indians were found to be significantly lower (0.17 and 0.11, respectively) compared to the frequencies in Caucasians (0.50 and 0.32, respectively) (P < 0.025). The frequency of E—(EcoRI) was similar to that in Caucasians (0.10 vs 0.15). A highly significant linkage disequilibrium was observed between the XbaI site and Ins/Del polymorphism of the apo B gene in this sample (X2= 31.9, P<0.001). The simultaneous presence of Del and X+ allele was significantly associated with higher body mass index (X2= 11.43, P<0.005), serum total cholesterol (X2= 5.11; P<0.025) and triglyceride (X2= 6.42; P< 0.025) levels. Mean values of adjusted BMI and serum triglyceride levels were found to be 29.0\pm1.92 vs 23.7\pm 0.67 (P<0.025) and 278.0\pm 60.78 vs 140.4\pm 15.43 mg/d1 (P<0.05), respectively, in subjects with Del and X+ compared to others. The multiple regression tests showed that 3.3 and 5.8% of the total variability of BMI is explained by Ins/Del and XbaI polymorphism, respectively, in this sample (P= 0.06 and 0.02), while 3.8% of serum triglyceride levels was explained by Ins/Del polymorphism of the apo B gene (P= 0.04). Further, the serum HDL cholesterol level was significantly associated with XbaI polymorphism, with X+ having significantly lower HDL cholesterol, and it explained about 5% of the total variability (P= 0.02).
Ambras syndrome: delineation of a unique hypertrichosis universalis congenita and association with a balanced pericentric inversion (8) (p11.2; q22)
Authors: Baumeister F. A. M. , Egger J. , Schildhauer M. T. , Stengel‐Rutkowski S.
Published: July 2010

Baumeister FAM, Egger J, Schildhauer MT, Stengel‐Rutkowski S. Ambras syndrome: delineation of a unique hypertrichosis universalis congenita and association with a balanced pericentric inversion (8) (p11.2; q22). Clin Genet 1993: 44: 121–128. © Munksgaard, 1993

Congenital hypertrichosis universalis is a rare autosomal dominant disease. We report the further development of a Greek girl, now aged 3 years, the first case associated with a balanced structural chromosomal aberration. She was described as a neonate by Sigalas et al. (1990). Her persistent generalized hypertrichosis is most excessive on the face, ears and shoulders. Her fine silky hair is of the vellus, not the lanugo type. The syndrome features are characterized, referring to nine further published case reports. It is distinguished from other types of congenital hypertrichoses, which have been described in the literature under different synonyms. To avoid confusion in the terminology, we propose to name this type of hypertrichosis Ambras syndrome in reference to the first documented family with congenital hypertrichosis universalis in the 16th century.
Anthropometric and craniofacial patterns in mentally retarded males with emphasis on the fragile X syndrome
Authors: Butler Merlin G. , Pratesi Riccardo , Watson Michael S. , Breg W. Roy , Singh Dharmdeo N.
Published: July 2010

Butler MG, Pratesi R, Watson MS, Breg WR, Singh DN. Anthropometric and craniofacial patterns in mentally retarded males with emphasis on the fragile X syndrome.

Clin Genet 1993: 44: 129–138. © Munksgaard, 1993

Anthropometric and craniofacial profile patterns indicating the percent difference from the overall mean were developed on 34 physical parameters with 31 white, mentally retarded males (23 adults and 8 children) with the fra(X) syndrome matched for age with 31 white, mentally retarded males without a known cause of their retardation. The fra(X) syndrome males consistently showed larger dimensions for all anthropometric variables, with significant differences for height, sitting height, arm span, hand length, middle finger length, hand breadth, foot length, foot breadth, and testicular volume. A craniofacial pattern did emerge between the two groups of mentally retarded males, but with overlap of several variables. Significant differences were noted for head circumference, head breadth, lower face height, bizygomatic diameter, inner canthal distance, ear length and ear width, with the fra(X) syndrome males having larger head dimensions (head circumference, head breadth, head length, face height and lower face height), but smaller measurements for minimal frontal diameter, bizygomatic diameter, bigonial diameter, and inner canthal distance. Several significant correlations were found with the variables for both mentally retarded males with and without the fra(X) syndrome. In a combined anthropometric and craniofacial profile of 19 variables comparing 26 white fra(X) syndrome males (13 with high expression (>30%) and 13 with low expression (<30%), but matched for age), a relatively flat profile was observed with no significant differences for any of the variables. Generally, fra(X) syndrome males with increased fragile X chromosome expression have larger amplifications of the CGG trinucleotide repeat of the FMR‐1 gene. No physical differences were detectable in our study between fra(X) males with high expression and apparently larger amplifications of the CGG trinucleotide repeats compared with those patients with low expression. Our research illustrates the use of anthropometry in identifying differences between mentally retarded males with or without the fra(X) syndrome and offers a comprehensive approach for screening males for the fra(X) syndrome and selecting those individuals for cytogenetic and/or molecular genetic testing.
Prenatal detection of an inverted X chromosome in a male
Authors: Brothman Arthur R. , Newlin Anna , Phillips Susan E. , Kinzie Gretchen Q. , Leichtman Lawrence G.
Published: July 2010

Brothman AR, Newlin A, Phillips SE, Kinzie GQ, Leichtman LG. Prenatal detection of an inverted X chromosome in a male. Clin Genet 1993: 44: 139–141. © Munksgaard, 1993

An unusual case of an X chromosome with a pericentric inversion (p11.3q21.3) was detected prenatally in a male fetus. This inversion has not been previously characterized. Although the inverted chromosome was transmitted through the mother, no living males on the maternal side were detected with the aberrant chromosome. Replication studies were performed on cultures of maternal peripheral blood lymphocytes, and it was determined that the inverted X chromosome was early replicating in approximately half of the cells. Following genetic counseling, the pregnancy was continued and a healthy male infant was delivered at term. Cytogenetic analysis of peripheral blood performed in the newborn period confirmed the prenatal findings. The child is developing normally at 3 years of age.
A family with autosomal dominant polycystic kidney disease not linked to chromosome 16p13.3
Authors: Jeffery Steve , Saggar‐Malik Anand K. , Morgan Steve , MacGregor Graham A.
Published: July 2010

Jeffery S, Saggar‐Malik AK, Morgan S, MacGregor GA. A family with autosomal dominant polycystic kidney disease not linked to chromosome 16p13.3.

Clin Genet 1993: 44: 173–176. © Munksgaard, 1993

A family of Sicilian origin with autosomal dominant polycystic kidney disease (APKD) has been shown to be unlinked to chromosome 16 markers. LOD scores for the polymorphic markers 3'HVR and SM7 flanking the PKD 1 locus, were ‐1.4 and ‐2.33 respectively, and θmax was 0.5 for each marker. The clinical phenotype of this family is consistent with that of the other non‐linked families with APKD reported in the literature, all outside the United Kingdom, which have a milder progression than those linked to 16p13.3. Assuming that a clinic population represents the most severe forms of a disease and non PKD‐1 is a less aggressive phenotype, the degree of genetic heterogeneity for APKD in the population may well be much greater than at present suggested.
The Myhre syndrome: report of two cases
Authors: Garcia‐Cruz D. , Figuera L. E. , Feria‐Velazco A. , Sánchez‐Corona J. , Garcia‐Cruz M. O. , Ramirez‐Duenãs R. M. , Hernandez‐Córdova A. , Ruiz M. X. , Bitar‐Alatorre W. E. , Ramirez‐Dueñas M. L. , Cantú J. M.
Published: July 2010

Garcia‐Cruz D, Figuera LE, Feria‐Velazco A, Sanchez‐Corona J, Garcia‐Cruz MO, Ramirez‐Dueñas RM, Hernandez‐Cordova A, Ruiz MX, Bitar‐Alatorre WE, Ramirez‐Dueñas ML, Cantu JM. The Myhre syndrome: report of two cases.

Clin Genet 1993: 44: 203–207. © Munksgaard, 1993

Two unrelated patients, aged 19 and 6 years, were studied and diagnosed as having Myhre syndrome (MS). This review, together with three previous cases, permits further delineation of MS. The main features are: short stature, mental retardation, blepharophimosis, muscular hypertrophy, decreased joint mobility, thick calvarium, broad ribs, hypoplastic iliac wings and short tubular bones. Advanced paternal age at the propositi's birth suggests an autosomal dominant mutation as the cause of MS.
Dacryocystitis associated with osteopoikilosis
Authors: Günal I. , Seber S. , Basaran N. , Artan S. , Günal K. , Gokturk E.
Published: July 2010

We report five members of a family with dacryocystitis associated with osteopoikilosis. The inheritance is autosomal dominant. Review of the literature revealed no other report of this kind of association. Osteopoikilosis must not be considered as a coincidental radiographic finding but as part of a systemic disorder.
Neither uniparental disomy nor skewed X‐inactivation explains Rett syndrome
Authors: Webb T. , Watkiss E. , Woods C. G.
Published: July 2010

Webb T, Watkiss E, Woods CG. Neither uniparental disomy nor skewed X‐inactivation explains Rett syndrome.

Clin Genet 1993: 44: 236–240. © Munksgaard, 1993

The locus DXS255 was studied using the probe M27β in ten probands with Rett syndrome and in eight of their families. No evidence of uniparental disomy of the X chromosome was detected, as all informative probands had inherited an allele from each of their parents. Differential methylation of a CCGG site within the DXS255 locus as shown by digestion with Mspl/Hpall, revealed moderate skewing of X‐inactivation favouring the maternal allele in two of the probands. Random X‐inactivation was present in all mothers tested and in two unaffected sisters. Three of four unaffected siblings had inherited the same maternal allele at DXS255.
Xbal polymorphism in DNA at the apolipoprotein B locus is associated with myocardial infarction (MI)
Authors: Bøhn M. , Bakken A. , Erikssen J. , Berg K.
Published: July 2010

Bøhn M, Bakken A, Erikssen J, Berg K. Xbal polymorphism in DNA at the apolipoprotein B locus is associated with myocardial infarction (MI).

Clin Genet 1993: 44: 241–248. © Munksgaard, 1993

High levels of low density lipoprotein (LDL) and its apolipoprotein B (apoB) are risk factors for atherosclerosis and myocardial infarction (MI). There is rich genetic polymorphism in apoB, first detected as the Ag allotypes of LDL, but today mostly examined at the DNA level. Genes contribute to the population variation in LDL and apoB levels and alleles in polymorphisms at the apoB locus are candidate genes with respect to control of lipid levels and susceptibility to atherosclerosis and MI. The Xbal polymorphism at the apoB locus, which involves the third base of threonin codon 2488 (ACC→ACT) without changing the amino acid sequence was examined in a case‐control study comprising 238 survivors of myocardial infarction (MI) and 621 controls. In univariate analysis, frequencies of genotypes in this polymorphism were not statistically different between patients and controls of either sex. However, in multivariate logistic regression analysis, the odds ratio X ‐ X ‐ homozygotes (homozygotes for absence of restriction site) for having MI compared to the pooled group of heterozygotes and X + X + homozygotes (homozygotes for presence of restriction site) was 2.16 (p = 0.007), after adjustments for age, sex, and levels of apoB, high density lipoprotein (HDL) cholesterol (HDLC) and Lp(a) lipoprotein. It appeared that heterozygotes do not have increased risk, compared to the X + X + homozygotes. Stratification according to low or high levels of apoB, HDLC and Lp(a) lipoprotein, showed that the X ‐ X ‐ genotype was more common in patients than controls, in all subgroups. We conclude that the X ‐ allele in double (but not in single) dose most probably increases the risk of MI. The increased risk is apparently not conferred by higher levels of total cholesterol, LDL or apoB, but through some variable or mechanism not closely related to traditional risk factors.
Application of fluorescence in situ hybridization for early prenatal diagnosis of partial trisomy 6p/monosomy 6q due to a familial pericentric inversion
Authors: Wauters J. G. , Bossuyt P. J. , Roelen L. , van Roy B. , Dumon J.
Published: July 2010

Wauters JG, Bossuyt PJ, Roelen L, van Roy B, Dumon J. Application of fluorescence in situ hybridization for early prenatal diagnosis of partial trisomy 6p/monosomy 6q due to a familial pericentric inversion. Clin Genet 1993: 44: 262–269. © Munksgaard, 1993

We report the prenatal diagnosis of a karyotype 46,XY,rec(6)dup p, inv(6) (p23q27) mat detected by fluoroscence in situ hybridization using chromosome 6pter and 6qter specific DNA markers. This partial duplication‐deletion (6p12→pter; 6q27→qter) emanated from a balanced pericentric inversion 46,XX inv(6) (p23q27)pat present in the mother. The phenotypes of two relatives with the same unbalanced anomaly are described. This report illustrates the sensitivity and specificity of fluorescence in situ hybridization (FISH) and its benefit in rapid and unequivocal prenatal diagnosis of subtle chromosomal rearrangements.
Familial syndactyly type III—report of a large pedigree
Authors: McKiernan M. V. , McCann J. J.
Published: July 2010

McKiernan MV, McCann JJ. Familial syndactyly type III—report of a large pedigree. Clin Genet 1993: 44: 270–271. © Munksgaard, 1993

We present a pedigree containing 14 cases of familial syndactyly of the ring and little finger (Type III syndactyly). Three of these were treated surgically in this unit, and a fourth had previously been treated elsewhere by the senior author of this paper. Analysis of the pedigree confirms the autosomal dominant nature of the genetic defect, while clinical study reveals variable phenotypical expression. This is one of the largest pedigrees yet reported for this variety of syndactyly.
Insertion /deletion (I/D) polymorphism at the locus for angiotensin I‐converting enzyme and parental history of myocardial infarction
Authors: Bøhn M. , Berge K. E. , Bakken A. , Erikssen J. , Berg K.
Published: July 2010

Bøhn M, Berge KE, Bakken A, Erikssen J, Berg K. Insertion/deletion (I/D) polymorphism at the locus for angiotensin I‐converting enzyme and parental history of myocardial infarction.

Clin Genet 1993: 44: 298–301. © Munksgaard, 1993

One hundred and eighty‐one male and 48 female myocardial infarction (MI) survivors and 172 male and 194 female controls were studied with respect to a possible association between premature parental MI (before age 61 years in mothers and/or before age 56 years in fathers) and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I‐converting enzyme (ACE). In the total series, the frequency of premature parental MI was 14% in the DD (homozygotes for the deletion (D) allele) genotypic group, 10.6% in the ID (heterozygotes) genotypic group and 6.1% in the II (homozygotes for the insertion (I) allele) genotypic group. In all males (male MI survivors and male controls combined), and in the total series, there was a significant excess of DD individuals as compared to II individuals among those with a parental history of premature MI (odds ratio 3.1 (p = 0.03) and 3.1 (p = 0.009), respectively). The ACE polymorphism may be an important genetic marker of MI risk and contribute to clustering of premature MI in families.
Immunofluorescence imaging diagnosis of Fabry heterozygotes using confocal laser scanning microscopy
Authors: Itoh Kohji , Kotani Masaharu , Tai Tadashi , Suzuki Hiroshi , Utsunomiya Toru , Inoue Hisako , Yamada Hideo , Sakuraba Hitoshi , Suzuki Yoshiyuki
Published: July 2010

Itoh K, Kotani M, Tai T, Suzuki H, Utsunomiya T, Inoue H, Yamada H, Sakuraba H, Suzuki Y. Immunofluorescence imaging diagnosis of Fabry heterozygotes using confocal laser scanning microscopy.

Clin Genet 1993: 44: 302–306. © Munksgaard, 1993

An immunofluorometric method was developed for the semiquantitative determination of trihexosylceramide in cultured fibroblasts from Fabry disease patients, using a laser scanning confocal imaging system. The accumulated glycolipid was detected as granular inclusions in the cells. Heterozygote identification was achieved both by counting of immunoreactive cells and by measuring the relative fluorescence intensity with a digital imaging system.
Twins and their mildly affected mother with Weaver syndrome
Authors: Dumić M. , Vuković J. , Cvitković M. , Medica I.
Published: July 2010

Dumić M, Vuković J, Cvitković M, Medica I. Twins and their mildly affected mother with Weaver syndrome. Clin Genet 1993: 44: 338–340. © Munksgaard, 1993

A pair of twins, a brother and sister, with the complete form of Weaver syndrome (overgrowth, macrocephaly, facial, skeletal, nail and feet anomalies) and their mildly affected mother are reported, suggesting autosomal dominant inheritance. They all have plantar and palmar hyper‐hydrosis and twins also have nail dysplasia, symptoms which have not yet been described in this syndrome.
Hypoalphalipoproteinaemia and polymorphisms associated with reduced expression of the apolipoprotein A‐I gene and resolution of disputed paternity in a large English family
Authors: Matsakis M. , Wile D. B. , Humphries S. E. , Winder A. F.
Published: July 2010

A Pst‐I RFLP polymorphism adjacent to the 3′ end of the apoliprotein A‐I gene is reported to associate with hypoalphalipoproteinaemia with dominant inheritance in families identified through accelerated coronary heart disease. This association was not apparent in a large English family identified through voluntary health screening, and with no evident premature coronary disease. Any association could, however, be masked by sex, or by further undetermined variation affecting Pst‐I restriction sites. Analysis of this and other polymorphisms present also led to resolution both of disputed paternity and of a long‐standing family feud.
A balanced autosomal translocation (3;9) associated with primary hypogonadism and dorsal spine stenosis
Authors: Hughes P. J. , Edwards J. M. Rice , Ridler M. A. C. , Lane R. J. M.
Published: July 2010

A man with a balanced translocation between chromosomes 3 and 9 associated with primary hypogonadism and dorsal spine stenosis is reported. The possible significance of this chromosomal abnormality is discussed.
Late‐onset familial amyloid polyneuropathy with the TTR Met 30 mutation in France
Authors: Grateau Gilles , Adams David , Malapert Denis , Viemont Michele , Deipech Marc , Said Gerard
Published: July 2010

Four unrelated French cases of familial amyloid polyneuropathy are reported. Clinical onset ranged from the sixth to the ninth decade. Sensory signs were predominant initially in the lower limbs; motor changes, and in one case autonomic involvement, appeared later. Amyloid disease was clinically limited to the peripheral nervous system. In two cases, there was no evidence of familial disease. DNA analysis was performed in these four patients and in two children of Patient 1. Restriction analysis of amplification products of exon 2 of the transthyretin gene was positive for the valine 30 to methionine mutation. These four unrelated patients live in different areas of France. Further studies are needed to determine whether these mutations have a common origin and whether they are related to the Portuguese mutation.
Early onset cerebellar ataxia with retained tendon reflexes: prevalence and gene frequency in an Italian population
Authors: Ohiò A. , Orsi L. , Mortara P. , Schiffer D.
Published: July 2010

A genetic epidemiologic analysis of early onset cerebellar ataxias (EOCA) with retained tendon reflexes was performed in a defined area of Northwestern Italy. Forty cases diagnosed from 1940 to 1990 were ascertained. The ascertainment probability was 85.7%. The segregation analysis (Weinberg's proband method and ‘singles” method under incomplete ascertainment) is compatible with autosomal recessive inheritance. The point prevalence ratio was 1.0/100000 population. The birth incidence rate was 1/48000 live births. Gene frequency was estimated to be 1/218. The ratio of first‐cousin marriages among parents of EOCA (4.5%) was lower than expected using Dahlberg's formula (8.9%).
A constitutional mutation within the retinoblastoma gene detected by PFGE
Authors: Janson Marie , Nordenskjöld Magnus
Published: July 2010

Retinoblastoma may be caused by constitutional mutations in the retinoblastoma gene which segregates as an autosomal dominant inherited predisposition for developing retinoblastoma tumours. Since 75% of these cases are new mutations, there is a need for methods to identify carriers of such germ‐line mutations, so that informed genetic counselling is available to patients and close relatives. We have used pulsed‐field gel electrophoresis in screening 20 unrelated cases with bilateral retinoblastoma. One constitutional mutation could be detected, and was found to be caused by a balanced chromosome (4; 13) translocation with the breakpoint within intron 17 of the retinoblastoma gene.
Prenatal detection of cri du chat syndrome on uncultured amniocytes using fluorescence in situ hybridization (FISH)
Authors: Pettenati Mark J. , Hayworth Rosa , Cox Kelly , Rao P. Nagesh
Published: July 2010

Fluorescence in situ hybridization (FISH) with a chromosome‐region‐specific DNA probe was used prospectively on uncultured amniocyte interphase cells to detect an unbalanced chromosome abnormality that resulted in cri du chat or 5p – syndrome. Confirmation was performed by routine cytogenetics.
Thyroid cancer in a case with the Alagille syndrome
Authors: Kato Zenichiro , Asans Junichi , Kato Tomomi , Yamaguchi Seiji , Kondo Naomi , Orii Tadao
Published: July 2010

A 19‐year‐old woman with the Alagille syndrome developed papillary thyroid carcinoma with lung metastasis. She was diagnosed as having Alagille syndrome at the age of 8. Following total thyroidectomy and lymph nodes dissection, iodine‐131 therapy was conducted for local and distant metastases. This is the first report of a case of thyroid cancer accompanying Alagille syndrome.
Chromosome instability in lymphocytes from patients with celiac disease
Authors: Fundia A. F. , Cid M. B. González , Bai J. , Gómez J. C. , Mazure R. , Vazquez K. , Larripa I. B. , Slavutsky I. R.
Published: July 2010

Cytogenetic studies were performed in celiac disease (CD) patients to determine if the presence of chromosome instability is related to the predisposition to cancer. Chromosome aberrations (CA) and sister chromatid exchange (SCE) frequencies in peripheral blood lymphocyte cultures from untreated CD patients and healthy controls were analyzed. Patients showed aberrations in 23% of cells, while only 3% were detected in the control group (p < 0.0001). The mean frequencies of gaps, breaks and total CA were found to be higher in CD patients compared to controls (p < 0.0001). Breakpoint distribution was nonrandom among chromosomes from celiac patients (p = 0.01), but not among controls (p = 0.04). The frequency of SCE/cell showed a mean value of 6.9 ± 0.6 in CD patients and 7.3 ± 0.2 in controls. No statistical differences were found. Breakpoints involved in CD patients presented a strong coincidence with the location of fragile sites (78.6%) and sites of cancer chromosome rearrangements (57.1%), most of them (75%) associated with malignant non‐Hodgkin lymphomas. These results suggest that CD is a condition with increased chromosome instability characterized by a high level of CA and normal SCE frequencies, probably related to the increased incidence of cancer.
Apolipoprotein B gene polymorphisms in ischemic heart disease and hypercholesterolemia: effects of age and sex
Authors: Hansen P. S. , Klausen I. C. , Lemming L. , Gerdes L. U. , Gregersen N. , Faergeman O.
Published: July 2010

The association of polymorphic alleles of the apolipoprotein B gene (Insertion/Deletion‐, Xbal‐, MspI‐, EcoRI‐, and 3′‐VNTR polymorphisms) with variation in lipid concentrations (total cholesterol (T‐C), HDL cholesterol (HDL‐C), and log‐triglycerides (TG)) in plasma was studied in 259 men and 59 women with moderate hypercholesterolemia (T‐C 5.5–8.0 mmol/l and TG < 2.5 mmol/l) and ischemic heart disease, especially in relation to the effect of sex and age. The XbaI and the Ins/Del polymorphic alleles were associated with variation in T‐C, but only in patients below the 75th percentile for age. The XbaI and Ins/Del polymorphic alleles were synergistically associated with variation in T‐C: the X+ and the Del alleles were associated with higher cholesterol concentrations. Younger male patients had the highest frequency of haplo‐types including both the X+ and the Del alleles, but the most striking difference was a significantly higher frequency of haplotypes including both the X — and the Ins alleles in female and in older male patients. The heterogeneity of association of polymorphic alleles in the apolipoprotein B gene to complex traits like hypercholesterolemia and ischemic heart disease in this study could explain why in most studies the X+ allele has been associated with higher cholesterol levels, whereas the X — allele has been associated with symptomatic atherosclerosis. The results of our study emphasize the importance of age and sex in measured genotype association studies.
Roberts‐SC phocomelia syndrome: a case with additional anomalies
Authors: Satar Mehmet , Atici Aytuğ , Bişak Ufuk , Tunali Nurdan
Published: July 2010

Roberts‐SC phocomelia syndrome (RS) is an autosomal recessive disorder with symmetric limb defects, craniofacial abnormalities, pre‐ and postnatal growth retardation and mental retardation. Patients with RS were reported to have premature separation of heterochromatin of many chromosomes. We report an infant whose clinical, radiologic and chromosomal findings resemble those of RS, with rudimentary gallbladder and accessory spleen. This patient may represent a variant of RS.
Variability gene effects of DNA polymorphisms at the apo B, apo AI/C III and apo E loci on serum lipids: the Cardiovascular Risk in Young Finns Study
Authors: Porkka Kimmo V. K. , Taimela Simo , Kontula Kimmo , Lehtimäki Terho , Aalto‐Setälä Katriina , Åkerblom Hans K. , Viikari Jorma S. A.
Published: July 2010

We studied the influence of selected genetic markers on the intra‐individual long‐term variability in serum lipid levels. The study cohort consisted of a sub‐sample from a large follow‐up study of atherosclerosis precursors in children and young adults. A total of 320 subjects had determinations of apo B XbaI RFLP genotypes, 305 subjects had apo AI/CIII SstI RFLP genotype determinations and 1581 subjects had their apo E phenotypes determined. Complete data on serum lipids were available at 3‐year intervals over a 6‐year follow‐up period. The subjects were healthy and aged 3–18 years at baseline. Intra‐individual variability was assessed with a nested analysis of variance procedure. Each of the genetic markers studied here significantly affected intra‐individual variability of serum lipid levels. No clear sex influence was observed, although the differences in variability tended to be more significant in males. Apo B XbaI genotypes significantly influenced intra‐individual variability of total and LDL‐cholesterol levels in both sexes. A marked effect of the XbaI geno‐type was also found on triglyceride variability. In males the standardized intra‐individual triglyceride variances were 0.71 and 0.34 in genotypes X1X1 and X2X2, respectively (p < 0.001), with a clear gene dosage effect. The apo AI/CIII genotype had an influence only on the variability of total cholesterol and LDL‐cholesterol levels and only in males. The apo E phenotypes were associated with intra‐individual variability in total and LDL‐cholesterol levels but again, only in males. The lowest variability was observed in the phenotype E4/3 where high mean values were also observed. We also examined the effect of combined genetic markers. Up to 7 times greater variability was found in the combination E3/2 + S1S1 compared to combination E4/3 + S1S2 (p < 0.001). In addition, mean levels of, e.g., LDL‐cholesterol were 70% greater in the combination of E4/3 +S1S2 compared to E3/2 + S1S1. This implies that subjects with both these genetic markers have high LDL‐cholesterol values that also tend to remain constantly elevated. In conclusion, it is evident that many of the presently known DNA polymorphisms of the coronary heart disease candidate gene loci also influence intraindividual variability of serum lipid or lipoprotein levels. These findings can be used to further refine our ability to predict the risk of a cardiovascular event.
The Charcot‐Marie‐Tooth syndrome: clinical aspects from a population study in South Wales, UK
Authors: MacMillan John C. , Harper Peter S.
Published: July 2010

The Charcot‐Marie‐Tooth (CMT) syndrome comprises a heterogeneous group of disorders affecting the peripheral nerves and anterior horn cells of the spinal cord. They constitute a significant proportion of the burden of disability caused by single gene neurological disorders, with a disease prevalence of 16.7 per 105 of the South Wales adult population. The clinical and genetic characteristics of these diseases in the population are described. In those cases identified as type I hereditary motor and sensory neuropathy (HMSN I), we have shown that it is possible to correlate disease severity with age, and that there is no clinical evidence for imprinting, manifest either in age of onset or disease severity.
Cerebro‐facio‐articular syndrome of Van Maldergem: confirmation of a new MR/MCA syndrome
Authors: Zampino Giuseppe , Colosimo Cesare , Balducci Francesca , Mariotti Paolo , Serra Fabrizio , Scarano Gioacchino , Mastroiacovo Pierpaolo
Published: July 2010

Van Maldergem et al. (1992) described a new syndrome in an 11‐year‐old girl, characterized by: mental retardation, hypotonia, dysmorphic facies with telecanthus, epicanthus, broad flattened nose, large inverted W‐shaped mouth, malformed ears, finger camptodactyly, and joint hyperlaxity. In this report we present a 5‐year‐old girl with very similar clinical findings. We confirm the existence of this condition as an independent clinical entity, and we propose that, based on the major clinical manifestations, it should be defined as “cerebro‐facio‐articular” syndrome.
Prader‐Willi‐like phenotype in fragile X syndrome
Authors: Schrander‐Stumpel Constance , Gerver Willem‐Jan , Engelen John , Mulder Hans , Fryns Jean‐Pierre
Published: July 2010

Henk Meyer1

A 3‐year‐old boy was referred to the pediatric department because of unexplained extreme obesity. Height and occipitofrontal circumference were just above the 90th centile. Endocrine studies failed to show any significant abnormality. Motor and speech development were generally delayed. On clinical‐cytogenetic‐molecular grounds, Prader‐Willi syndrome was excluded. Fragile X syndrome was diagnosed by the presence of the classical FMR‐1 mutation and confirmed by cytogenetic studies, revealing 20% fragile X positive cells. We compare the clinical features in the present patient with the nine reported patients with fra(X) syndrome and extreme obesity. In pathogenesis, hypothalamic dysregulation is hypothesized. In differential diagnosis of Prader‐Willi syndrome, fragile X has to be considered, especially when laboratory workup for Prader‐Willi syndrome is negative. Clinical behavior can be of help.
Discordance between direct and PHA‐stimulated chromosome preparations from neonates
Authors: Garnham I. W. , Fernandez H. , Callen D. F. , Haan E. A. , Sutherland G. R.
Published: July 2010

Four examples of discordance between karyotypes prepared from direct and PHA‐stimulated neonatal blood samples are presented. The specimens were initially studied by direct methods to establish a neonatal karyotype rapidly. The patients are described and the significance of the findings is discussed.
The apolipoprotein C‐II variant apoC‐IILys19→Thr is not associated with dyslipidemia in an affected kindred
Authors: Zysow Bernice R. , Pullinger Clive R. , Hennessy Lori K. , Farese Robert V. , Ghassemzadeh Marjan , Kane John P.
Published: July 2010

The rare apolipoprotein C‐II (apoC‐II) mutation, apoC‐IILys19→Thr, also known as apoC‐II‐v, has been found previously in association with hyperlipoproteinemia. From a lipid clinic screening we identified three unrelated individuals who had the apoC‐IILys19→Thr mutation. Among eight family members of one proband, we have found another four who were affected. None of the inviduals in this kindred is dyslipidemic and there is no difference in lipid levels between affected and unaffected family members. Therefore, we conclude that the presence of this apolipoprotein variant by itself has no effect on lipoprotein levels. In addition, the apolipoprotein E (apoE) isoform, apoE4 does not have a synergistic effect on lipoprotein levels in this kindred, in contrast to observations on the interaction of apoE4 with another apoC‐II mutant (apoC‐IIToronto). The single nucleotide substitution that causes the apoC‐IILys19→Thr variant introduces a previously unrecognized restriction site (for Mae III), that provides for easy screening.
Patient and parental attitudes toward genetic screening and its implications at an adult cystic fibrosis centre
Authors: Conway S. P. , Allenby K. , Pond M. N.
Published: July 2010

General population screening for cystic fibrosis carrier status in the United Kingdom would detect 72% of at‐risk couples. Proper counselling would allow these couples to make informed reproductive choices, including the possibility of prenatal diagnosis and the termination of an affected pregnancy. However, children with cystic fibrosis born in this decade, given optimum treatment, now have an average life expectancy of 40 years, and there is no unanimity of opinion on how, where, when, or even if, screening should be offered. The purpose of this questionnaire‐based study was to examine the attitudes of an adult clinic population who have grown up with cystic fibrosis, and of their parents, towards genetic screening programmes and the controversies and ethical dilemmas surrounding such programmes in cystic fibrosis. Both patients and parents supported prenatal screening (88% and 90%) and the option of terminating an affected pregnancy (68% and 84%). Only 22% of patients and 10% of parents felt that screening should be limited to families with a history of cystic fibrosis, and 19% and 6%, respectively, that prenatal diagnosis should be restricted to those with a previous child with cystic fibrosis. Despite the negative aspects of any screening programme and the acknowledged ethical problems peculiar to cystic fibrosis, the conclusion of our patients and parents who have lived intimately with the illness is that there should be the option of utilising information available from genetic screening for cystic fibrosis to guide reproductive choices. Pilot programmes to define the optimum management of such screening should continue.
Melkersson‐Rosenthal syndrome and de novo autosomal t(9;21)(p11;p11) translocation
Authors: Smeets E. , Fryns J. P. , Van den Berghe H.
Published: July 2010

In this report we describe a 26‐year‐old female with the typical clinical symptoms and signs of Melkersson‐Rosenthal syndrome, an autosomal dominant disorder with variable expression, and a de novo t(9;21)(p11;p11), and suggest that the “Melkersson‐Rosenthal gene” is located at 9p11.
Central nervous system abnormalities in chromosome deletion at 11q23
Authors: Ono Jiro , Harada Koushi , Hasegawa Tomoko , Sakurai Kosuke , Kodaka Ryuhei , Tanabe Yuji , Tanaka Junko , Igarashi Takayasu , Nagai Toshisaburo , Okada Shintaro
Published: July 2010

Two Japanese pediatric patients with terminal deletion of the long arm of chromosome 11 are described. Both had the morphological abnormalities of the 11q deletion syndrome, such as prominent epicanthal folds, broad flat nasal bridge with short, upturned nose, short philtrum with carp‐shaped mouth, cardiac anomalies and nonprogressive moderate psychomotor developmental delay. Patient 1 is the first case to be reported with 11q deletion with serial magnetic resonance (MR) examinations of cerebral white matter. The initial MR imaging studies demonstrated multiple areas of T1 and T2 prolongation in the cerebral white matter in both patients at the ages of 2 5/12 and 2 1/12 years, respectively. A second MR imaging, performed 1 year after the first in Patient 1, demonstrated slight improvement of the lesions. Neither patient showed clinical deterioration. These results suggest that the lesions were caused by delayed myelination, rather than by demyelination. It is suggested that an unknown factor which is important for myelination is located on the long arm of chromosome 11: perhaps the neural cell adhesion molecule (NCAM).
Characterization of β‐thalassemia mutations by denaturing gradient gel electrophoresis: patterns in the Mediterranean mutations
Authors: Dozy Andrée M. , Kan Yuet Wai
Published: July 2010

Of the many methods which have been devised to detect point mutations, we use reverse dot blot for β‐thalassemia in our laboratory. In any mutation detection program, rare or new mutations outside of a laboratory's repertoire will be encountered. Denaturing gradient gel electrophoresis (DGGE) is one of the methods used to localize such mutations. We describe the DGGE electrophoresis pattern of eight common Mediterranean β‐thalassemia mutations and the βs and βc mutations, and the definition of two rare mutations outside of these ten. We believe that DGGE is a useful adjunct for mutation detection.
Familial occurrence of Hirschsprung's disease
Authors: Russell Michael Bjern , Russell Charlotte Astrid , Fenger Kirsten , Niebuhr Erik
Published: July 2010

We assessed the familial occurrence of Hirschsprung's disease from 224 probands born in Denmark after 1959. Probands who were still alive received a mailed questionnaire, and medical reports for the probands and their relatives with suspected Hirschsprung's disease were examined. The diagnosis of Hirschsprung's disease required a histologically verified biopsy or surgical colonic specimens, and exclusion of a secondary causes for Hirschsprung's disease. Familial occurrence was seen in 11 families. Ten first‐degree, two third‐degree and one fifth‐degree relatives had Hirschsprung's disease. Both short segment agangliosis (the sigmoid colon or below) and long segment agangliosis (above the sigmoid colon) occurred in five of the 11 families, implying that the etiology of Hirschsprung's disease with short and long segment agangliosis is the same. Compared with the general population, the first‐degree relatives of the 224 probands had a minimum of a 93‐fold increased risk of Hirschsprung's disease. This strongly suggests that genetic factors play a role in Hirschsprung's disease
Mixed gonadal dysgenesis and cell line differentiation. Case presentation and literature review
Authors: Sugarman I. D. , Crolla J. A. , Malone P. S.
Published: July 2010

A male patient with mixed gonadal dysgenesis, involving a streak gonad on the right and a histologically normal testis in the left, was found to have a 45, X/46, X, dic(Yp) chromosome constitution on peripheral blood cultures. Fibroblasts grown from both gonads showed the “normal” testicular tissue to have e 45, X/46, X, dic(Yp), whereas the cells from the streak gonad were all 45, X. The structure of the dic(Yp) chromosome was confirmed using non‐isotopic in situ hybridization with Y centromere and Yp specific probes. On hormonal stimulation, testosterone levels rose by 50%. The “normal” testis was left in situ, but close follow up will be required in view of the malignant potential.
Traversing the biological complexity in the hierarchy between genome and CAD endpoints in the population at large
Authors: Sing Charles F. , Zerba Kim E. , Reilly Sharon L.
Published: July 2010

An emerging challenge facing those who are concerned about the efficacy of public health programs is to understand how information from the DNA revolution might be used to improve our ability to predict the initiation, progression and severity of a common disease having a complex multifactorial etiology. In the course of research to evaluate the role of information about DNA, combinations of genome types and environmental exposures that predispose to disease will be identified. Such information is expected to be useful in efforts to identify individuals and families at higher risk of disease and to predict their responses to a proposed therapy. This paper begins with a discussion of the features of a realistic biological model for the study of a common multifactorial disease. We present evidence for the complexity in the relationship between genome type variation and variation in risk of coronary artery disease (CAD) and review the preliminary results of our studies to determine whether information about genome type variation can improve our ability to predict the distribution of CAD among individuals in the population at large. Such studies make it apparent that new analytical strategies are necessary to deal with the plethora of genome type information available for the evaluation of risk of a common disease like CAD. This shift in the research paradigm will build upon new strategies to understand the organization of natural systems that are coming from outside the mainstream of genetic research.
Apolipoprotein(a): structural and functional consequences of mutations in kringle type 10 (or kringle 4–37)
Authors: Scanu Angelo M. , Edelstein Celina
Published: July 2010

The size polymorphism of Lp(a) is well recognized. It is now apparent that there is an additional polymorphism resulting from mutations occurring at the kringle level. One of these mutations involves a trp72 to arg substitution in apo(a) kringle type 10 and is attended by a defective binding of Lp(a) to immobilized lysine/fibrin. Other mutations affecting the other amino acids of the “lysine‐binding pocket” may have similar functional consequences and may be important at the clinical level in terms of thrombogenesis.
Genetic and environmental influences on LDL subclass phenotypes
Authors: Austin Melissa A.
Published: July 2010

There is accumulating evidence that subclasses of low‐density lipoproteins (LDL) are important in atherosclerosis. Several case‐control studies have demonstrated that a predominance of small, dense LDL (LDL subclass phenotype B) is associated with increased risk of coronary heart disease (CHD). Phenotype B is also consistently characterized by an atherogenic lipoprotein phenotype, including increased levels of plasma triglyceride and decreased high‐density lipoprotein cholesterol. Family studies and genetic linkage studies demonstrate that LDL subclasses are influenced by a single major gene effect, although this locus (or loci) remain to be definitively mapped. Twin studies confirm the presence of genetic effects, but also show that non‐genetic influences are important. Hypolipidemic drugs, beta‐blockers, diet and exercise, in particular, appear to influence the expression of LDL subclass phenotypes. This combination of genetic and environmental influences may provide opportunities to develop targeted intervention strategies to reduce CHD risk among genetically susceptible individuals.
The XbaI polymorphism at the apolipoprotein B locus and risk of atherosclerotic disease
Authors: Behn M. , Berg K.
Published: July 2010

A restriction fragment length polymorphism (RFLP) in DNA at the apolipoprotein B (apoB) locus detectable with the restriction enzyme XbaI involves the third base of threonin codon 2,488 (ACC ACT) (Priestley et al. 1985, Blackhart et al. 1986, Carlsson et al. 1986). The allele lacking the XbaI site (the X— allele) is associated with reduced levels of total cholesterol (TC), low density lipoprotein (LDL) apoB and possibly triglycerides (Law et al. 1986, Berg 1986, Paulweber et al. 1990, Peacock et al. 1992). Paradoxically, the same allele has been reported to be more common in survivors of myocardial infarction (MI), patients with coronary heart disease (CHD), and patients with peripheral arterial disease, than in controls. In 4 out of 11 studies reported in the literature, there was a statistically significant association between the X — allele and atherosclerotic disease, and a trend towards association was present in all but one of the remaining studies (Table 1).
Sister chromatid exchange in families with Angelman or Prader‐Willi syndrome
Authors: Webb Tessa
Published: July 2010

Using estimation of numbers of sister chromatid exchanges arising in 15q 11 q 13 as a measure, comparisons of the stability of the Prader‐Willi syndrome critical region have been made. The groups studied included probands with Prader‐Willi or Angelman syndromes either with or without a cytogenetically visible deletion in 15q11q13, their parents, specifically those parents who had passed on the homologue which had become deleted, and a control group. No significant differences were found between any of the four groups, indicating that there was no increase in the instability of the PWSCR region as measured by sister chromatid exchange.