bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitreous involvement in familial amyloidotic neuropathy: a genealogical and genetic study
Authors: Sandgren Ola , Drugge Ulf , Holmgren Gösta , Sousa Alda
Published: July 2010

Extended genealogical studies stretching back to the 17th century were performed concerning the heredity patterns of vitreous involvement in Swedish patients with familial amyloidotic polyneuropathy (FAP). FAP is an autosomal dominant inherited disorder, characterized by extracellular deposition of amyloid and a clinical syndrome of peripheral and autonomic neuropathy. In addition, some patients show typical vitreous opacities. All patients had their origin in a restricted geographical area. Some main patterns arose from this study: 1) Patients who had vitreous opacities as the first symptom of FAP seem to form a separate group, with a distinct age of onset distribution; 2) The familial occurrence of vitreous opacities raises the possibility that other familial factors modify the expression of the FAP gene; 3) The mean age of onset for vitreous opacities is lower for homozygous than for heterozygous patients.
Wolman disease: morphological, clinical and genetic studies on the first Scandinavian cases
Authors: Röyttä M. , Fagerlund A. S. , Toikkanen S. , Salmi T. T. , Jorde L. B. , Forsius H. R. , Eriksson A. W.
Published: July 2010

On the Åland Islands, a 1‐month‐old girl was diagnosed as having Wolman disease. The diagnosis was confirmed neurochemically; a decreased activity of acid lipase was noted in the proband and her parents had typical carrier values. This is the first Scandinavian case reported. The skin biopsy revealed cytoplasmic accumulations identical to those noted in two sibs who highly probably had Wolman disease during the 1950s. Both these sibs died at the age of about 3 months and presented a heavy accumulation of lipid material in lymph nodes, spleen, adrenal glands, liver, gut, and also some pathological alterations in other organs. Electron microscopic findings from deparaffinized samples showed cytoplasmic accumulation of lipid material similar to that noted in Wolman disease. Genealogical analyses revealed that the index families had ancestors from the same restricted area and also common ancestors during the 17th century. The parents of the two affected sibs were born on a small island and were related in many different ways. On the basis of genealogical studies and other genetic investigations performed, the importance of founder and drift effect for manifestations of rare hereditary disorder in isolates is stressed.
Amyloidogenic and non‐amyloidogenic transthyretin Asn 90 variants
Authors: Alves I. L. , Almeida M. R. , Skare J. , Skinner M. , Kurose K. , Sakaki Y. , Costa P. P. , Saraiva M. J. M.
Published: July 2010

Recently, a new transthyretin (TTR) variant was described in the normal Portuguese and German populations. The same substitution was found associated with familial amyloidotic polyneuropathy (FAP) in an American family of Italian origin. Comparative isoelectric focusing studies showed a difference in the mobility pattern between the non‐pathogenic and pathogenic variants. However, comparative DNA sequencing between them did not reveal any additional mutation. Comparative isoelectric focusing between the variants and TTR Asn 90 produced by recombinant techniques indicated that the non‐pathogenic variant has the electrophoretic behaviour expected for the mutation. We suggest that an as yet unknown post‐translational modification may have occurred in the FAP‐associated Asn 90 variant, turning it into an amyloidogenic molecule.
Elevated serum levels of creatine kinase BB in autosomal dominant osteopetrosis Type II — a family study
Authors: Yoneyama Tatsuo , Fowler Hilton L. , Pendleton John W. , Sforza Peter P. , Gerard Roy D. , Lui Charles Y. , Eldridge Thomas H. , Iranmanesh All
Published: July 2010

A markedly elevated BB isoenzyme fraction of serum creatine kinase was noted in four male siblings and correlated with typical radiographic findings of autosomal dominant osteopetrosis Type II (ADO Type II). Patients with other sclerosing bone diseases had no elevation of CK‐BB. The precision of the electrophoretic mobility patterns and correlation by I‐125 tagged radioimmunoassay method confirms that this is CK‐BB. We postulate that the dysfunctional and/or immature osteoclasts in ADO are more dependent on CK‐BB than on the usual tricarboxylic acid cycle for the production of energy. The correlation of marked elevation of serum CK‐BB with radiographic evidence of ADO Type II may prove to be of value as a biologic marker in the early diagnosis of the illness and lead to better understanding of the metabolism of bone.
DNA screening of hyperlipidemic Afrikaners for familial hypercholesterolemia
Authors: Kotze M. J. , Langenhoven E. , Kriek J. A. , Oosthuizen C. J. J. , Retief A. E.
Published: July 2010

Three different point mutations of the low‐density lipoprotein receptor (LDLR) gene are responsible for familial hypercholesterolemia (FH) in about 90% of Afrikaner patients. Screening of hyperlipidemic Afrikaner individuals for these founder‐related mutations was performed to determine the distribution of the mutations in individuals with different lipid profiles, and to provide guidelines for screening of the mutations in hyperlipidemics. Rapid DNA methods, based on restriction enzyme analysis or allele‐specific hybridisation of enzymatically‐amplified genomic DNA, have been used to analyse the LDLR gene mutations in four groups of Afrikaner individuals. Group 1 included 84 individuals in whom FH was diagnosed on clinical data. Groups 2–4 included 89 hyperlipidemic individuals who did not fulfil the criteria for inclusion in the FH study group. The founder‐related LDLR gene mutations were present in 36% of the hyperlipidemics whose clinical diagnosis excluded them from the FH study group. This indicates that conventional methods for the diagnosis of FH, based mainly on lipid determinations and a family history of coronary heart disease, do not always allow an accurate diagnosis of the disease. Screening of hyperlipidemic Afrikaner individuals for specific founder‐related LDLR gene mutations can provide a definite diagnosis of FH, which may lead to better counselling and optimal treatment.
Confirmation of true mosaic trisomy 20 in a phenotypically normal liveborn male
Authors: Brothman Arthur R. , Rehberg Kimberly , Storto Patrick D. , Phillips Susan E. , Mosby Robert T.
Published: July 2010

A new case of prenatally detected mosaic trisomy 20 (79% trisomy 20 cells in amniocyte cultures) that was confirmed in newborn tissue is presented. A healthy male infant was delivered at term, with no dysmorphology or apparent malformations; this baby is developing normally. Twenty‐five percent of foreskin and 17% of fetal cord cells also showed trisomy 20, while no trisomic cells were detected in newborn blood. High frequency mosaicism for trisomy 20 in this case was thus due to true embryonic origin. Extensive counseling and prenatal follow‐up in this case led to an unaffected liveborn, and guarded optimism may be warranted for future cases of mosaic trisomy 20 detected prenatally.
Pitted enamel hypoplasia in tuberous sclerosis
Authors: Sampson J. R. , Attwood D. , Mughery A. S. Al , Reid J. S.
Published: July 2010

Thirty patients with tuberous sclerosis (from 29 different families) were examined for evidence of macroscopically visible pitted enamel hypoplasia. Of 23 patients with permanent teeth, 11 (48%) showed multiple enamel pits (mean 4.6 pits, range 3–9), but none were seen in six patients with deciduous teeth. Five of 563 controls (0.88%) had similar pitted enamel hypoplasia. Simple dental examination may be a useful adjunct in the assessment of patients with permanent teeth when a diagnosis of tuberous sclerosis is being considered, but is less likely to be helpful in the pre‐school child.
A novel truncated apolipoprotein B (apo B55) in a patient with familial hypobetalipo‐proteinemia and atypical retinitis pigmentosa
Authors: Talmud Philippa J. , Converse Carelya , Krul Elaine , Huq Luhna , McIlwaine Gawn G. , Series John J. , Boyd Patricia , Schonfeld Gustav , Dunning Alison , Humphries Steve
Published: July 2010

We have identified an apolipoprotein (apo) B mutation in a patient with an atypical form of retinitis pigmentosa (RP). In the family the eye disease is characterised by late age of onset and autosomal dominant inheritance. In addition to RP, the proband has low total cholesterol (4.5 mmol/1) and LDL‐cholesterol (2.0 mmol/1) levels characteristic of the autosomal codominant apolipoprotein (apo) B deficiency disease hypobetalipoproteinemia (HBL). Using a monoclonal antibody directly against apo B and immunoblots of SDS polyacrylamide gel separated plasma, a normal apo B100 and a truncated apo B species with an estimated size of apo B54 was identified in the proband and his RP‐affected sister. The location of the mutation in the apo B gene was identified using chemical cleavage of mismatch and this was confirmed by direct sequencing of an amplified fragment of DNA spanning the estimated site of the mutation. The mutation is a C→T transition at nucleotide 7692 which changes the CGA arginine2495 codon to a STOP codon resulting in the premature termination of apo B100. The truncated apo B protein is 2494 amino acids long with a predicted size of apo B55. Using allele specific oligonucleotides and oligonucleotide melting techniques, the proband, his sister and two other relatives out of a total of 20 family members, screened for the presence of the apo B55 mutation, were heterozygous for the mutation. The segregation of the apo B55 allele was confirmed in the family using the 3′ variable number of tandem repeats of the apo B gene. The RP‐affected brother of the proband did not have the apo B mutation, and thus we conclude that the eye disease in this family is not co‐segregating with the HBL. The possible effect of the lipid abnormality on the development of RP in this family is discussed.
A study of ten small supernumerary (marker) chromosomes identified by fluorescence in situ hybridization (FISH)
Authors: Rauch A. , Pfeiffer R. A. , Trautmann U. , Liehr T. , Rott H. D. , Ulmer R.
Published: July 2010

In seven cases additional minute chromosomes studied by FISH were identified as no. 3, 11, 15, 18, 21 and X. Findings were unexpected except for partial trisomy 21 in an adolescent with minor features of Down's syndrome. Moreover, an i(18p) in a mentally retarded dysmorphic child and an idic(15) in a child with Fallot tetralogy was confirmed. In a child with r(21), a supernumerary marker was shown to be derived from no. 21, while in the mother an additional marker idic(22) was noted.
Prevalence of retinitis pigmentosa in Slovenia
Authors: Peterlin B. , Cankl‐Klain N. , Morela V. , Stirn B. , Rainer S. , Cerar V.
Published: July 2010

Two hundred and twenty‐nine symptomatic patients with retinitis pigmentosa were ascertained in Slovenia between 1986 and 1990. Twenty‐three further patients were identified while data from 63 families (82 patients) were being collected. After correction for underascertainment, a prevalence of 1 in 6023 was estimated in the Slovene population (1999 477 in 1990). The highest prevalence of 1 in 1902 was found in the age group 65 years and older. Of 63 analysed families, 17 (27%) showed autosomal dominant, 13 (21%) autosomal recessive, and one family (1.5%) X‐linked inheritance; in 30 families (47.5%) isolated cases were found; and in two families the mode of inheritance was impossible to determine.
Reassessment of a chromosome 12q + marker by fluorescent in situ hybridization (FISH)
Authors: Jaziorowska A. , Houck G. E. , Yao X.‐L. , Sklower‐Brooks S. L. , Wisniewski K. E. , Jenkins E. C. , Wisniewski H. M.
Published: July 2010

We present a case previously described by Jenkins et al. (1983) as atypical Down syndrome (DS). The initial diagnosis was first made on the basis of phenotypic and cytogenetic data. This analysis was supported by studies of superoxide dismutase (SOD1) activity that maps to band 21q22.1. Results from phenotypic, chromosome banding and SODI studies suggested a karyotype of 46,XX,—12, + t(12pter to 12qter::21q21 to 21q22.?2). Using fluorescent in situ hybridization (FISH) for chromosome painting with DNA libraries derived from sorted human chromosomes to stain selectively the chromosomes No. 21 and No. 12, we demonstrate that the marker chromosome 12q+ has no chromosome 21 content but it is derived from chromosome 12.
The gene for Best's macular dystrophy is located at 11q13 in a Swedish family
Authors: Forsman Kristina , Graff Caroline , Nordström Stefan , Johansson Kent , Westermark Eleonora , Lundgren Erik , Gustavson Karl‐Henrik , Wadelius Claes , Holmgren Gösta
Published: July 2010

A large Swedish family with more than 250 cases of Best's macular dystrophy has been clinically and genetically studied. The gene was traced to a couple born in central Sweden in the 17th century. Highly significant evidence for genetic linkage to DNA markers on chromosome 11q13 was detected. A lod score of 15.12 was obtained at recombination fraction 0.01 with DNA marker INT2 (also called FGF3). The retinally expressed gene ROM1, which maps to the same chromosomal region is a candidate for this genetic disease.
Digito‐reno‐cerebral syndrome: confirmation of Eronen syndrome
Authors: Le Merrer M. , David A. , Goutieres F. , Briard M. L.
Published: July 2010

In 1985, Eronen et al. described a new autosomal recessive syndrome with absence of the distal phalanges of the toes and fingers, renal defect and cerebral anomalies (dilated ventricles or seizures). Two unrelated children affected by this syndrome enable us to accept its autonomy and delineate its nosology. Variability of the expression of the renal and cerebral manifestations is emphasized.
Autosomal inheritance of “senile” retinitis pigmentosa. A report of a family with consanguinity
Authors: Bonneau Dominique , Kaplan Josseline , Girard Georges , Dufier Jean‐Louis
Published: July 2010

We describe two sisters affected with retinitis pigmentosa of late onset. Night blindness and progressive visual field loss occurred after 50 years of age in both cases. The parents of affected individuals were first cousins and there was no known history of other similar cases in previous generations. Autosomal recessive inheritance is suggested for such senile retinitis pigmentosa.
Clinical variability of cardio‐facio‐cutaneous syndrome: report of two additional cases
Authors: Ghezzi Monica , Parenti Giancarlo , de Franchis Raffaella , Farina Vincenzo , de Leva Francesco , Guarino Alfredo , Canani Roberto Berni , Strisciuglio Pietro
Published: July 2010

We describe two new cases of cardio‐facio‐cutaneous (CFC) syndrome, and underline the clinical variability of the CFC phenotype in our two patients presenting with border‐line psychomotor development. The first patient showed some additional clinical manifestations, such as cryptorchidism and scoliosis, and the second one had atypical skin lesions.
A new polymorphism in exon 11 of the LDL receptor gene in healthy people and in familial hypercholesterolemia subjects
Authors: Leren Trond P. , Solberg Kari , Røby Oddveig , Rødningen Olaug K. , Tonstad Serena , Ose Leiv , Berg Kåre
Published: July 2010

We have screened exon 11 of the low density lipoprotein receptor (LDLR) gene from familial hypercholesterolemia (FH) heterozygotes for point mutations by using analysis of single strand conformation polymorphisms (SSCP). A variant pattern was observed in three out of 39 subjects. By DNA sequencing, this variant pattern was found to be due to a C→T transition at nucleotide 1617 that affects the third base of codon 518. A PCR method was developed to screen FH heterozygotes and normal subjects for this mutation. The gene frequencies in FH heterozygotes and normal subjects were 4% and 4.5%, respectively. Thus, the mutation cannot be in linkage disequilibrium with a mutation that causes FH. Rather, the mutation may be a useful genetic marker at the LDLR locus. Haplotype analysis at the LDLR locus in two FH families where the proband possessed the mutation revealed that the mutation was on two different haplotypes. This finding is consistent with the mutation occurring at a mutational hot spot.
De novo interstitial deletion 16(q12. 1q13) of paternal origin in a 10‐year‐old boy
Authors: Schuffenhauer Simone , Callen David F. , Seidel Heide , Shen Yang , Lederer Gabriele , Murken Jan
Published: July 2010

A 10‐year‐old boy with a de novo del(16)(q12.1q13) and many features of the deletion 16q phenotype is described. The deletion occurred in a paternal chromosome as demonstrated by DNA studies with polymorphic (AC)n microsatellite repeat markers. Comparison with published cases suggests that deletion of either of two regions (q13 and q22.1) on the long arm of chromosome 16 is associated with an apparently identical phenotype. No parental imprinting of this region was demonstrated.
Detection of the Pro664‐Leu mutation in the low‐density lipoprotein receptor and its relation to lipoprotein(a) levels in patients with familial hypercholesterolemia of Dutch ancestry from The Netherlands and Canada
Authors: Defesche J. C. , van de Ree M. A. , Kastelein J. J. P. , van Diermen D. E. , Janssans N. W. E. , van Doormaal J. J. , Hayden M. R.
Published: July 2010

From a large cohort of hyperlipidemic patients, who attended the Lipid Research Clinic in Amsterdam, The Netherlands and in Vancouver, Canada, 915 consecutive patients with familial hypercholesterolemia (FH) of Dutch descent, were selected. This group of FH patients was screened for the presence of a cytosine to thymidine nucleotide substitution in exon 14 of the LDL‐receptor gene, in order to determine the frequency of this mutation in patients of Dutch descent and to investigate the relationship between the mutation and the level of lipoprotein(a). The mutation was detected in seven individuals. All patients with this mutation shared the same haplotype, which is suggestive of an ancient mutation. The index patients and a large kindred with this mutation were further analyzed at the biochemical and clinical level. Except for total and LDL‐cholesterol, there was no statistically significant difference in biochemical parameters between family members with and without FH. In contrast to previous reports, there was no difference in plasma levels of lipoprotein(a) between patients with the mutation in exon 14 and unaffected individuals.
The Wolf‐Hirschhorn syndrome in fetuses
Authors: Tachdjian G. , Fondacci G. , Tapla S. , Huten Y. , Blot P. , Nessmann C.
Published: July 2010

Wolf‐Hirschhorn syndrome (WHS) with partial deletion of the short arm of chromosome 4 has been exceptionally diagnosed in fetuses. We report prenatal diagnosis of five cases of monosomy 4p. The fetuses were karyotyped for severe intrauterine growth retardation (IUGR) diagnosed on routine ultrasound (US). In addition, cleft‐lip and palate and diaphragmatic hernia respectively were found in two cases. The quantity of amniotic fluid was normal in all cases. At autopsy, the fetuses showed the typical craniofacial dysmorphy but without microcephaly. Major renal hypoplasia was the only constant visceral anomaly. Midline fusion defects were observed in all the fetuses, ranging from minor abnormalities such as scalp defect, hypertelorism, pulmonary isomerism, common mesentery, hypospadias and sacral dimple, to cleft palate, corpus callosum agenesis, ventricular septal defect, and diaphragmatic hernia. On post‐mortem X‐rays, a delayed bone age was always observed. All the placentae were hypotrophic, and two exhibited vascular lesions, although there was no maternal hypertension. Chromosomal studies showed that the breakpoints were within the 4p16 band in three cases, the 4p15 band in one case, and the 4p14 band in one case. The deletion was de novo in four cases, and resulted from a paternal translocation in one case. This study emphasizes the importance of karyotyping all fetuses with IUGR, especially when the quantity of amniotic fluid is normal, and suggests the possibility of recognizing on US the particular phenotype of WHS in utero.
A 9.6 kilobase deletion in the low density lipoprotein receptor gene in Norwegian familial hypercholesterolemia subjects
Authors: Rødningen Olaug K. , Røshy Oddveig , Tonstad Serena , Ose Leiv , Berg Kåre , Leren Trond P.
Published: July 2010

Haplotype analysis of the low density lipoprotein receptor (LDLR) gene was performed in Norwegian subjects heterozygous for familial hypercholesterolemia (FH). Southern blot analysis of genomic DNA, using an exon 18 specific probe and the restriction enzyme Ncol, showed that two out of 57 unrelated FH subjects had an abnormal 3.6 kb band. Further analyses revealed that this abnormal band was due to a 9.6 kb deletion that included exons 16 and 17. The 5′ deletion breakpoint was after 245 bp of intron 15, and the 3′ deletion breakpoint was in exon 18 after nucleotide 3390 of cDNA. Thus, both the membrane‐spanning and cytoplasmatic domains of the receptor had been deleted. A polymerase chain reaction (PCR) method was developed to identify this deletion among other Norwegian FH subjects. As a result of this screening one additional subject was found out of 124 subjects screened. Thus, three out of 181 (1.7%) unrelated Norwegian FH subject possessed this deletion. The deletion was found on the same haplotype in the three unrelated subjects, suggesting a common mutagenic event. The deletion is identical to a deletion (FH‐Helsinki) that is very common among Finnish FH subjects. However, it is not yet known whether the mutations evolved separately in the two countries.
X‐inactivation in girls with Rett syndrome
Authors: Kormann‐Bortolotto M. H. , Woods C. G. , Green S. H. , Webb T.
Published: July 2010

Cytogenetic studies have been carried out on a series of nine girls with Rett syndrome, six of their mothers and nine normal female controls. No abnormality of the X‐chromosome has been observed in any subject. X‐inactivation studies using various methods of detecting the timing of individual band replication were performed. The overall pattern seen was essentially the same in all subjects, but in the patients with Rett syndrome there may be an alteration in the timing of the X‐inactivation process in the region Xp11.3 or 4→Xp21.
Screening for the apolipoprotein B‐100 arginine3500→ glutamine mutation in patients with type III hyperlipoproteinemia
Authors: Feussner Giso , Schuster Herbert
Published: July 2010

Forty‐three patients with clinically and biochemically unequivocally defined type III hyperlipoproteinemia (HLP) were screened for the presence of the apolipoprotein (apo) B‐100 arginine3500→ glutamine mutation. This receptor‐binding defective apolipoprotein B variant is the cause of familial defective apo B‐100 (FDB), an autosomal dominantly inherited disease, which leads to increased plasma cholesterol levels and premature atherosclerosis. Neither patient expressed FDB. It is concluded that the gene defect responsible for FDB is not involved in the pathogenesis of type III HLP.
Genotyping of spinal muscular atrophy families with linked DNA probes
Authors: Gennarelli Massimo , Melchionda Salvatore , Fattorini Cristina , Novelli Giuseppe , Dallapiccola Bruno
Published: July 2010

We report on linkage analysis and haplotype characterization in 40 Italian families with spinal muscular atrophy (SMA). The investigated loci included D5S6, D5S112, D5S39, and D5S76. No evidence of unlinked families was found. Thirty‐two (80%) of the examined families were fully informative for prenatal diagnosis and carrier detection. The frequencies of individual alleles did not differ between SMA and normal chromosomes.
Reevaluation of the origin of a marker chromosome in a patient with 47,XX,r(13)(p11q34), +mar by molecular cytogenetics
Authors: Cooper L. F. , Coss C. A. , Jabs E. W.
Published: July 2010

A chromosomal fragment in a patient with a ring chromosome 13 and clinical features of monosomy 13q3 syndrome was analyzed by in situ hybridization techniques and was found to be a marker chromosome with a functional centromere originating from chromosome 13.
Cytogenetic and dermatoglyphic findings in a familial case of hypomelanosis of Ito (incontinentia pigmenti achromians)
Authors: Vormittag Walter , Ensinger Christian , Raff Manfred
Published: July 2010

Cytogenetic and dermatoglyphic investigations were performed in a mother (M.B.) and her daughter (D.B.), who were both suffering from hypomelanosis of Ito (incontinentia pigmenti achromians; HI). Whereas quite normal chromosomal results could be obtained after culture of peripheral lymphocytes, a diploid/tetraploid mosaicism (46,XX/92,XXXX) was found in cultured skin‐fibroblasts derived from a hypopigmented skin area of M.B., with a slowly decreasing tetraploidy rate in the course of passaging: #2 23%, #5 11%, #11 and #14 6% and #18 and #21 2%. In cultures of normally pigmented skin, only single tetraploid cells could be detected. Dermatoglyphic examinations in both patients showed single transverse creases, a high number of secondary creases and a longitudinal alignment of the main line A bilaterally, and there was a tricentric fingertip pattern on the right digit III of M.B., i.e. a pattern which occurs very seldom in human beings. The results are discussed in respect to the clinical‐diagnostic overlap of HI and incontinentia pigmenti Bloch‐Sulz‐berger.
Population variation and genetics of plasma homocyst(e)ine level
Authors: Berg Káro , Malinow M. Rans , Kiarulf Pater , Upson Barbara
Published: July 2010

A high level of plasma hoinocyst(e)ine (H(e)) has been reported to be an independent risk factor for coronary heart disease (CHD), at least in some populations. We have determined the H(e) concentration in the plasma of two series of Norwegians in order to establish a baseline for future analysis of people with CHD. The mean sex‐ and age‐adjusted homocyst(e)ine level was 10.6 (range 4.84–29.88) in one series and 10.5 (range 3.76–40.57) in the other. The H(e) level appeared to be independent of other proven or potential risk factors or protective factors with respect to CHD. The intraclass correlation coefficient in monozygotic (MZ) twins is a (possibly inflated) estimate of heritability. We have examined two series of MZ twins. The intraclass correlation coefficient was significant in both series. In one series, the Pearson correlation coefficient was 0.53 and the Kendall correlation coefficient 0.38.

In the other, the values were 0.56 and 0.46, respectively. We conclude that in the population examined, H(e) levels exhibit significant heritability.
Severe pre‐ and postnatal growth retardation, developmental delay with hypotonia and marked hypotrophy of the distal extremities, dental anomalies, and eczematous skin. A new autosomal recessive entity
Authors: Grubben C. , da Cecil P. , Borghgrae M. , van den Berghe H. , Fryns J. P.
Published: July 2010

Grubben C, De Cock P, Borghgraef M, Van den Berghe H, Fryns JP. Severe pre‐ and postnatal growth retardation, developmental delay with hypotonia and marked hypertrophy of the distal extremities, dental anomalies and eczematous skin. A new autosomal recessive entity. Clin Genet 1992:41: 16–21.

We report on three young children, two girls and one boy, with pre‐ and postnatal growth deficiency, hypotonia, psychomotor retardation with notably impaired speech development, hypotrophy of the distal extremities, small hands and feet, small and widely spaced teeth, eczematous skin, and, in two of them, a partial agenesis of the corpus callosum. To our knowledge this specific combination of features has not been reported before. Since the two girls are sisters and the boy is the product of a consanguineous marriage, the inheritance of this new syndrome appears to be autosomal recessive.
Further evidence consistent with Yqh as an indicator of risk of gonadal blastoma in Y‐bearing mosaic Turner syndrome
Authors: de Arce Miguel A. , Costigan Colm , Gosden John R. , Lawler Mark , Humphries Peter
Published: July 2010

De Arce MA, Costigan C, Gosden JR, Lawler M, Humphries P. Further evidence consistent with Yqh as an indicator of risk of gonadal blastoma in Y‐bearing mosaic Turner syndrome. Clin Genet 1992:41:28–32.

An 8‐year‐old girl with some features of Turner syndrome and karyotype 45X/46XY had developed a bilateral gonadoblastoma in her rudimentary ovaries. Her normal Y chromosome showed the characteristic distal fluorescence, as seen in her father's. Another mosaic, this time 45X/46XidicY, and also with some Turner features had rudimentary ovaries, but no gonadoblastoma had developed at age 14.

The nature of her idicY, which showed no fluorescent distal Yq and had one of the centromeres inactivated, was confirmed by in situ hybridisation with a Yp‐specific probe. Using primers from a human Yp‐specific sequence, we amplified DNA extracted from paraffin‐embedded ovarian tissue from both cases, and from a normal testicle and a normal ovary as controls. The finding of the expected Y‐derived PCR product in the rudimentary gonads from these mosaic patients indicates the presence of their Y chromosome in both. We discuss the validity of the findings, and the possible role of sequences in or near the fluorescent part of Yq in the origin of gonadoblastoma in Y‐bearing mosaic Turner syndrome.
Severe Silver‐Russell syndrome and translocation (17;20) (q25;q13)
Authors: Ramírez‐Dueñas M. L. , Medina C. , Ocampo‐Campos R. , Rivera H.
Published: July 2010

Ramírez‐Dueñas ML, Medina C, Ocampo‐Campos R, Rivera H. Severe Silver‐Russell syndrome and translocation (17;20)(q25;q13). Clin Genet 1992:41: 51–53.

An 8‐year‐8‐month‐old girl with Silver‐Russell syndrome (SRS) and a paternally inherited balanced t(17;20)(q25;q13) is described. This observation suggests that an SRS gene(s) maps on chromosome 17 or 20 and that the patient phenotype resulted from either unmasking of heteroz‐ygosity or genomic imprinting via paternal disomy.
Oculocerebral syndrome with hypopigmentation (Cross syndrome): report of a new case
Authors: Lerone M. , Possagno A. , Taccone A. , Poggi G. , Romeo G. , Silengo M. C.
Published: July 2010

Lerone M, Pessagno A, Taccone A, Poggi G, Romeo G, Silengo MC. Oculocerebral syndrome with hypopigmentation (Cross syndrome): report of a new case. Clin Genet 1992: 41: 87–89.

A syndrome of ocular and cutaneous hypopigmentation, severe mental retardation with spastic tetraplegia and athetosis was first observed by Cross in three siblings of an inbred Amish family. Since then, seven other patients, three, sporadic and four with familial recurrence, have been reported in the literature, confirming the autosomal recessive inheritance. The clinical spectrum of the syndrome has been expanded to include true developmental defects of the CNS such as cystic malformation of the posterior fossa of the Dandy‐Walker type. We report a new case of Cross syndrome.
No effect of a Taql polymorphism in DNA at the endothelin I (EDN1) locus on normal blood pressure level or variability
Authors: Berge K. L. , Berg K.
Published: July 2010

Berge KE, Berg K. No effect of a Taql polymorphism in DNA at the endothelin I (EDN1) locus on normal blood pressure level or variability. Clin Genet 1992: 41: 90–95.

Endothelin is a peptide reported to be one of the most potent vasoconstrictors known. Presumably, endothelin could play a role in the physiological regulation of blood pressure in healthy or hypertensive people. We have studied a normal restriction fragment length polymorphism (RFLP) at the endothelin‐I (EDN1) locus detected with the restriction enzyme Taql. In three different series comprising 166, 120 and 207 unrelated individuals, we found no evidence for association between genotype in this polymorphism and level of systolic or diastolic blood pressure. In two series of 156 and 117 monozygotic (MZ) twin pairs, respectively, there was no difference between genotypes in within‐pair variation in systolic or diastolic blood pressure. Thus neither “level gene” nor “variability gene” effects of normal genes at the EDN1 locus could be detected with the polymorphism analyzed, in healthy population samples.
Experiences with risk estimates for carriers of chromosomal reciprocal translocations
Authors: Midro Alina T. , Stengel‐Rutkowski Sabine , Stene Jon
Published: July 2010

Midro AT, Stengel‐Rutkowski S, Stene J. Experiences with risk estimates for carriers of chromosomal reciprocal translocations. Clin Genet 1992:41: 113–122.

The risk estimates for individual carriers of ten different familial reciprocal translocations detected among 500 couples with reproductive failures are presented. These were established by application of the empirical data analysed by Stengel‐Rutkowski et al. (1988) and the guidelines given in Stene & Stengel‐Rutkowski (1988). Different risks were estimated for unbalanced offspring at birth or at second trimester prenatal diagnosis for abortions, or stillbirths/early deaths. These risk estimates varied considerably from translocation to translocation. Carriers of five translocations had risks for offspring with single‐segment imbalances. The birth risk figures ranged from 0.1% to 13.8%. Carriers of five other translocations had risks for double‐segment imbalances with birth risks ranging from 0% to 3.2%. The estimated risk figures were independent of the method of ascertainment. Among the parents of the index cases we found nine maternal carriers and only one paternal carrier. This presentation illustrates the need for individual risk counselling of each carrier with reciprocal translocation regarding further family planning.
The trichorhinophalangeal syndrome with repeated dislocation of the patella
Authors: Puliyel Jacob M. , Puliyel Matthew M. , Varughese Sara
Published: July 2010

Puliyel JM, Puliyel MM, Varughese S. The trichorhinophalangeal syndrome with repeated dislocation of the patella. Clin Genet 1992: 41: 139–142.

The trichorhinophalangeal syndrome associated with laxity of the skin and joints has been mistaken for Ehlers‐Danlos syndrome (Jones 1988). We report a case of the trichorhinophalangeal syndrome which we mistook for the Larsen syndrome. Literature and published photographs of the Larsen syndrome are reviewed to highlight the similarities between these two entities. These observations may be of value in the genetic mapping of the Larsen syndrome, which perhaps is a contiguous gene syndrome.
A new chromosome 9 variant: an extra band within the 9qh region
Authors: Hoo Joe J.
Published: July 2010

Hoo J J. A new chromosome 9 variant: an extra band within the 9qh region. Clin Genet 1992: 41: 157–158.

An extra G‐positive band within the 9qh regions is reported as a new chromosome 9 variant. This variant may have been more prevalent than has hitherto been perceived. Due to its small size, this extra band might not be readily recognizable in routine G‐staining.
Monosomy 6q: report on four new cases
Authors: Valtat C. , Galliano D. , Mettey R. , Toutain A. , Moraine C.
Published: July 2010

Valtat C, Galliano D, Mettey R, Toutain A, Moraine C. Monosomy 6q: report on four new cases. Clin Genet 1992:41: 159–166.

We report on four patients with partial monosomy of the long arm of chromosome 6: two children presenting with an interstitial deletion del(6)(ql4ql6), the two others presenting with a terminal deletion del(6)(q25qter). These patients are compared with previous reports in the literature: 16 cases of terminal deletion and 17 cases of interstitial deletion. The deletions most often occur de novo. Mental retardation is always described. Dysmorphic facial features range between minor and major. There may be associated visceral abnormalities. After comparing the size and the localisation of the deletions with clinical data, we are now able to suggest a clinical localisation on chromosome 6.
Phenotypic discriminants in the Waardenburg syndrome
Authors: Winsbip Ingrid , Brighton Peter
Published: July 2010

Winship I, Beighton P. Phenotypic discriminants in the Waardenburg syndrome. Clin Genet 1992: 41: 181–188.

The gene for Waardenburg syndrome (WS) has been assigned to the locus 2q37 and further molecular investigations of affected families are now urgently required to explore the question of possible genetic heterogeneity. Firm positive or negative diagnosis in family members is crucial for studies of this type, but great variation in phenotypic expression sometimes makes this a difficult matter. Ethnic variation in craniofacial anatomical relationships further complicates the issue. We have attempted to establish diagnostic criteria for WS on the basis of an analysis of the phenotypes in 68 affected children who have been examined in special schools for the deaf in Southern Africa during the past 18 years. We then used these criteria for diagnostic evaluation of all available persons in seven multigeneration WS families in the Cape, as a preliminary to molecular investigations. With very few exceptions this approach permitted firm positive or negative diagnosis in these individuals.
Biochemical investigation of a Brazilian patient with a defect in mitochondrial acetoacetyl‐coenzyme‐A thiolase
Authors: Walner Moacir , Sansavsrlno Maria Tareza , Glugliani Roberto , Sweetman Laurence , Yamaguchl Seljl , Fukao Toshiyukl , Shlh Vivian E.
Published: July 2010

Wajner M, Sanseverino MT, Giugliani R, Sweetman L, Yamaguchi S, Fukao T, Shih VE. Biochemical investigation of a Brazilian patient with a defect in mitochondrial acetoacetylcoenzyme‐A thiolase. Clin Genet 1992: 41: 202–205.

A case report of 3‐ketothiolase deficiency due to a defect of mitochondrial acetoacetyl‐CoA thiolase protein in a Brazilian boy and its biochemical investigation is presented. The child had moderate generalized hypotonia, EEG alterations and crises of metabolic acidosis following infections. Hypotonia and EEG abnormalities disappeared with a low protein diet, and physical and mental development are normal. Urinary organic acid excretion was typical of 3‐ketothiolase deficiency, showing consistently high levels of 2‐methyl‐3‐hydroxybutyric acid and tiglylglycine. Activation of acetoacetyl‐CoA thiolase activity by potassium (K) ion in cultured fibroblasts was not observed, demonstrating the lack of activity of mitochondrial acetoacetyl‐CoA thiolase. In addition, the signal for the mitochondrial acetoacetyl‐CoA thiolase protein was undetectable in the immunoblot analysis. In the pulse‐chase experiments, the signal for mitochondrial acetoacetyl‐CoA thiolase was detected after a 1‐h pulse but not after a 24‐h chase. These results indicate that the deficiency was caused by an unstable mitochondrial acetoacetyl‐CoA thiolase protein.
Transmission of breast cancer ‐ a controversy resolved
Authors: Iselius Lenaart , Littler Mary , Morton Newton
Published: July 2010

Iselius L, Littler M, Morton N. Transmission of breast cancer ‐ a controversy resolved. Clin Genet 1992:41: 211–217.

The Danish breast cancer data collected by Jacobsen (1946) have been reanalysed using morbid risks which incorporate mortality due to breast cancer. A dominant gene is favoured for familial breast cancer, supporting the conclusions of Williams & Anderson (1984) and later authors. Neglect of specific mortality does not greatly alter estimates of gene frequency and displacement, but the evidence for a major gene is inflated. No evidence for heterogeneity was found. Earlier claims of non‐Mendelian transmission are in error since we have discovered that transmission probabilities are not correctly implemented in the computer program POINTER. Cases with bilateral breast cancer and males with breast cancer all belonged to families favouring a major gene. Of the cancer sites frequently reported to be associated with familial breast cancer, only ovarian cancer is significant in this material.
Polymorphisms at the GLUT2 (β‐cell/liver) glucose transporter gene and non‐insulin‐dependent diabetes mellitus (NIDDM): analysis in affected pedigree members
Authors: Baroni Marco G. , Alcolado Juan C. , Pozzilli Paolo , Cavallo Maria G. , Li Shu‐Ri , Galton David J.
Published: July 2010

The precise genetic defects underlying the etiology of non‐insulin‐dependent diabetes mellitus (NIDDM) have yet to be identified. The β‐cell/ liver glucose transporter gene GLUT2 represents a good candidate for the etiology of the disease, being involved in the glucose signalling for β‐cell insulin release. Population association studies of the GLUT2 gene in NIDDM have so far yielded controversial results. In order to determine the possible contribution of this gene to the inheritance of NIDDM, we have employed a new approach, where two polymorphic markers of the GLUT2 locus, detected with the restriction enzyme Taq‐1, were examined for linkage with the disease in a group of 22 Italian pedigrees with affected members (n = 50). Departure from independent segregation between markers and disease was analyzed by the Affected‐Pedigree‐Members (APM) statistical method. Furthermore, association analysis between the Taq‐I RFLPs at the GLUT2 locus and NIDDM was performed in a group of diabetics with a strong family history, comprising the 22 probands and 23 other diabetics with an affected first‐degree relative. The results indicate that there was no segregation distortion between the Taq‐1 markers of the GLUT2 gene and the disease in the pedigrees examined. Also, no significant difference in genotype distribution, haplotype and allele frequencies was found between diabetics and controls for the two Taq‐1 RFLPs. We conclude that genetic variation at the GLUT2 transporter gene is unlikely to contribute in a major way to the inheritance for NIDDM in this Italian population.
Lethal congenital erythroderma: a newly recognised genetic disorder
Authors: Shield J. P. H. , Jndge M. R. , Reardon W. , Baraitsar M. , Nohria V. , Malons M. , Harper J. I.
Published: July 2010

We report 4 patients and their extended families comprising 17 cases, all of whom had congenital exfoliative erythroderma resistant to treatment, associated with failure to thrive and hypoalbuminaemia. All died in the first year of life. This condition appears to be inherited in an autosomal recessive manner and the underlying defect remains unknown.
Neu‐Laxova syndrome: report of a case from Turkey
Authors: Kuseyri F. , Bilge I. , Bilgiç L. , Apak M. Y.
Published: July 2010

Kuseyri F, Bilge I, Bilgiç L, Apak MY. Neu‐Laxova syndrome: report of a case from Turkey.

Clin Genet 1993: 43: 267–269. © Munksgaard, 1993

We describe a case of Neu‐Laxova syndrome in a newborn female who was born at full‐term to consanguineous Turkish parents. The pathological and radiological features are described.
Prenatal diagnosis of congenital sialidosis
Authors: Sasagasako N. , Miyahara S. , Saito N. , Shinnoh N. , Kobayashi T. , Goto I.
Published: July 2010

Sasagasako N, Miyahara S, Saito N, Shinnoh N, Kobayashi T, Goto I. Prenatal diagnosis of congenital sialidosis.

Clin Genet 1993: 44: 8–11. © Munksgaard, 1993

A case of prenatally diagnosed congenital sialidosis is described in a 21‐week‐old male fetus, which was the fifth product of non‐consanguineous parents. The proband, the second product, was diagnosed as having sialidosis by the enzyme assay in peripheral leukocytes after birth. At the 17th week of pregnancy, the fetus at risk was proven to have isolated sialidase deficiency after analyzing a sample of the cultured amniotic fluid cells. There were many cytoplasmic vacuoles and increased amounts of sialyloligosaccharides in the tissue of the aborted fetus, while the amount and the pattern of gangliosides in the central nervous system were normal.
Congenital contractural arachnodactyly in two double second cousins: possible homozygosity
Authors: Bistritzer Tzvy , Fried Kalman , Lahat Eli , Dvir Michaela , Goldberg Michael
Published: July 2010

Bistritzer T, Fried K, Lahat E, Dvir M, Goldberg M. Congenital contractural arachnodactyly in two double second cousins: possible homozygosity.

Clin Genet 1993: 44: 15–19. © Munksgaard, 1993

A Bedouin family with two girls affected by severe congenital contractural arachnodactyly (CCA) is described. The girls were double second cousins. One of the girls also had ambiguous genitalia, an anomaly not generally associated with this disorder. The two children were both the product of first‐cousin Bedouin parents from the same family. It is possible that both sets of parents were heterozygous for CCA; thus the infants may have been homozygous for CCA, which is usually an autosomal dominant condition. No instance of homozygous CCA has previously been reported. This family suggests genetic heterogeneity in CCA and that, in some rare families, the mode of inheritance may be autosomal recessive.
Proposed: an international code of ethics for medical genetics
Authors: Wertz Dorothy C. , Fletcher John C.
Published: July 2010

Wertz DC, Fletcher JC. Proposed: an international code of ethics for medical genetics.

Clin Genet 1993: 44: 37–43. © Munksgaard, 1993
Frontonasal malformation and reciprocal translocation t(15;22)(q22;q13)
Authors: Fryns J. P. , Kleczkowska A. , van den Berghe H.
Published: July 2010

Clin Genet 1993: 44: 46–47. © Munksgaard, 1993
Parental origin of the supernumerary chromosome in trisomy 18
Authors: Ya‐gang Xie , Robinson Wendy P. , Spiegel Roland , Binkert Franz , Ruefenacht Urszula , Schinzel Albert A.
Published: July 2010

Ya‐gang X, Robinson WP, Spiegel R, Binkert F, Ruefenacht U, Schinzel AA. Parental origin of the supernumerary chromosome in trisomy 18. Clin Genet 1993: 44: 57–61. Munksgaard, 1993

The parental origin of an extra chromosome in Edwards syndrome has been investigated in 23 families by the combination of the VNTR probe pERT25, two microsatellite polymorphisms for D18S34 and D18S40, and several two‐allele polymorphisms. Of the 23 cases, 22 were informative, with 17 (77%) being maternal and 5 (23%) paternal in origin. These results support the previous investigations, suggesting that trisomy 18 is predominantly of maternal origin, although a higher rate of paternally derived cases was observed than previously reported. A significant increase in maternal age was found to be associated with meiotic nondisjunction. Parental age was increased in both the maternally and paternally derived cases, but the size of the latter class was small and did not reach statistical significance.
Infertility in carriers of two bisatellited marker chromosomes
Authors: Gentile M. , Susca F. , Resta N. , Stella A. , Cascone A. , Guanti G.
Published: July 2010

Gentile M, Susca F, Resta N, Stella A, Cascone A, Guanti G. Infertility in carriers of two bisatellited marker chromosomes.

Clin Genet 1993: 44: 71–75. © Munksgaard, 1993

Two unrelated sterile patients, a male and a female, with karyotypes characterized by the presence of two supernumerary bisatellited marker chromosomes, were studied with the aid of fluorescence in situ hybridization (FISH). Using alphoid centromeric specific probes, the markers were identified as an idic (15) (pter‐q 11) and a mar (14). In both cases a single accessory bisatellited marker was present in the karyotype of one of the parents. A possible correlation between the excess of constitutive heterochromatin and meiotic disturbances in the two patients is discussed.