bluuebunny/crossref_metadata_2025 huggingface dataset:
Apparent Fryns' syndrome and aneuploidy: evidence for a disturbance of the midline developmental field
Authors: Dean J. C. S. , Couzin D. A. , Gray E. S. , Lloyd D. J. , Stephen G. S.
Published: July 2010

A premature male infant is described in whom the presence of coarse facies, diaphragmatic hernia, genital anomalies and Dandy‐Walker malformation suggested a diagnosis of Fryns' syndrome. Lymphocyte karyotype revealed a partial trisomy 22, and his mother carried an apparently balanced 11/22 translocation. Three infants have been described recently with features of Fryns' syndrome and various aneuploidies. It is suggested that amplified developmental instability of the midline developmental field may account for some of the phenotypic resemblances between these cases.
De novo 13q partial duplication identified by cytogenetic, biochemical and molecular approaches
Authors: Schwartz S. , Harris M. , Ehrenpreis R. , Zaslav A. , Raffel L. J. , Schwartz M. F. , Lieber E. , Cohen M. M.
Published: July 2010

A 3.5‐month‐old female infant manifesting dysmorphic facies, developmental delay and failure to thrive was referred for cytogenetic evaluation. Peripheral lymphocytes revealed three chromosomally distinct cell lines: 46,XX/46,XX,10p+/47,XX,10p +, + mar. Dermal fibroblasts revealed only the 46,XX,10p+cell line. High resolution G‐, R‐, and Q‐banding suggested that the extra chromosomal material (10p+) represented a duplication of the segment 13q14→13qter. Parental karyotypes were normal. As absolute identification of de novo chromosomal abnormalities, based solely on cytogenetic studies, is sometimes difficult, both biochemical and molecular approaches were undertaken to elucidate this abnormality in more detail. Dosage effects were examined using esterase D (localized to 13q14.1) and the DNA probes p1E8 and p9A7 (localized to 13q22 and 13q31/32, respectively). These studies suggested the presence of only 2 copies of esterase D, but 3 copies of both DNA probes, allowing identification of the breakpoint at 13q14.2.
Genetic mapping of loci for X‐linked retinitis pigmentosa
Authors: Dahl N. , Sundvall M. , Pettersson U. , Andréasson S. , Anvret M. , Kugelberg U. , Hagbyhn‐Gericke A. , Goonewardena P.
Published: July 2010

Linkage analysis was performed in three Swedish families segregating for X‐linked retinitis pigmentosa (XLRP), using five polymorphic DNA markers assigned to Xp. Individual recombination events were analyzed and two‐ and five‐point linkage analysis was undertaken. In one family, a XLRP locus was mapped to the same position as OTC corresponding to RP3. In two families, a disease locus linked to OTC was excluded. In one family, recombination events indicate a locus for XLRP outside the interval (DXS84‐OTC‐DXS255‐DXS14), most likely on the centromeric side of DXS14.
Cohen syndrome: fertility in a female patient
Authors: Fryns J. P. , Lemmens F. , van den Berghe H.
Published: July 2010

In this report we describe fertility in an adult female with Cohen syndrome. She gave birth to a son, now 1.5 years old, with discrete facial stigmata and slight psychomotor retardation.
Diagnostic reliability of the cytogenetic centromere heteromorphism in the human X chromosome
Authors: Friedrich U. , Larsen T. B. , Nielsen J.
Published: July 2010

The reliability of the centromere marker was tested in 22 parents and their daughters with Turner's syndrome. The segregation of the centromere marker was compared to the results found by RFLP analysis, and there was complete agreement in all 19 informative cases.
Y‐derived sequence detected in minute chromosomes by polymerase chain reaction and in situ hybridization
Authors: Tsukahara Masato , Matsuura Shinya , Kishi Fumio , Fisher Lynda K. , Stock A. Dean , Izumikawa Yoshinori , Naritomi Kenji , Kajii Tadashi
Published: July 2010

A 10‐year‐old girl and a 10‐month‐old girl, both with ambiguous genitalia, were found to have 45,X/46,X,mar and 45,X/46,X,r(?) mosaicism. The marker chromosomes in both girls were very small. Polymerase chain reaction, with synthetic oligonucleotide primers from Y‐specific DNA sequences pY‐80 and pY53.3 containing the sex‐determining region Y(SRY), proved the marker chromosomes to contain the Y short arm material. In situ hybridization with probe pY‐80 confirmed that the marker chromosomes included the Y short arms. These findings, together with ambiguous genitalia in the girls, indicate that the marker chromosomes include the testis‐determining factor gene.
Occipital scalp defect associated with valvular pulmonary stenosis. A new entity?
Authors: Fryns J. P. , de Cock P. , van den Berghe H.
Published: July 2010

We present a 6‐month‐old, developmentally retarded male with a congenital scalp defect and associated valvular pulmonary stenosis. Review of the literature revealed one other report on a newborn with the same apparently unique association.
Cleft palate and complex chromosome rearrangements
Authors: Kousseff Boris G. , Papenhausen Peter , Neu Richard L. , Essig Yau‐Ping , Saraceno Carmelo A.
Published: July 2010

Two of three unrelated children with de novo congenital complex chromosome rearrangements (CCR) with more than four chromosome breaks had cleft lip and palate as one of several congenital anomalies. In patient 1, unilateral complete cleft of the primary and secondary palates accompanied severe ectrodactyly, bilateral posterior choanal atresia and several minor congenital anomalies. Karyotypes of peripheral lymphocytes and skin fibroblasts showed five derivative chromosomes with six break points. There were two translocations, t(2;5), t(3;11) and an interstitial deletion, del(13)(q12q14). Patient 2 had a bilateral complete cleft of the lip and palate, in addition to slow pre‐ and postnatal growth and minor congenital anomalies. Peripheral lymphocytes and palatal mucosa fibroblasts karyotypes showed five derivative chromosomes with six break points. A partial deletion of 10p, two translocations, t(2;3), t(7;18) and an inversion of the derivative chromosome 2 were present. In both patients, a “major catastrophe” of unknown etiology in one of the parental gametes appeared to be the event leading to the stable CCR without evidence of persistent chromsome instability. All four parents had normal karyotypes. The presence of palatal clefts in these patients indicates that dysmorphologists and pediatricians have to consider CCR whenever taking care of a patient with cleft palate, particularly if additional anomalies, no matter how subtle, are present. The detection and interpretation of the latter anomalies are essential for the diagnosis and management of these patients. Accurate cytogenetic diagnosis determines the short‐ and long‐term prognosis and facilitates genetic counseling in regard to life‐span, quality of life and reproductive plans of patients and parents.
Leber hereditary optic neuropathy: estimation of number of embryonic precursor cells and disease threshold in heterozygous affected females at the X‐linked locus
Authors: Bu Xiangdong , Rotter Jerome I.
Published: July 2010

LHON has been suggested to involve both mitochondrial and X‐chromosome‐linked loci. By extending two‐locus mitochondrial and nuclear gene analytic methods, we recently proposed that a proportion of affected females are likely heterozygous at the X‐linked locus and affected due to unfortunate X‐chromosome inactivation. Assuming that the optic tissue is the primary site of action of the mutant gene(s), we further propose here that there should be no fewer than six embryonic precursor cells for the involved optic tissue at the stage in early development when X‐chromosome inactivation occurs. We also estimate that the disease threshold (i.e. proportion of cells with abnormal X‐chromosome active in the responsible tissue at the time of X‐chromosome inactivation) for a heterozygous female is in the range of 0.60 to 0.83.
Autosomal recessive microcephaly with early onset seizures and spasticity
Authors: Silengo M. , Lerone M. , Martinelli M. , Martucciello G. , Caffarena P. E. , Jasonni V. , Romeo G.
Published: July 2010

We describe two siblings, a male and a female pair, born of consanguineous parents, affected with a rare genetic form of congenital microcephaly. The clinical syndrome is characterized by early onset myoclonic seizures, spasticity, and profound psychomotor retardation without detectable brain malformations. To date, only two kindreds and one sporadic case with a similar clinical picture have been observed and reported (Tolmie et al. 1987, Bundey & Griffiths 1977). The severity of the neurological features and their perinatal onset differentiate the syndrome from the more common autosomal recessive microcephaly with spasticity/seizures.
The Charcot‐Marie‐Tooth syndrome: perceptions of disability and projected use of DNA diagnostic tests
Authors: MacMillan John C. , Harper Peter S.
Published: July 2010

The Charcot‐Marie‐Tooth group of disorders cause significant morbidity in a proportion of the individuals affected. We have shown that there is a significant correlation between the objective neurological assessment of their dysfunction and the individual's subjective perception of their disability. We have also documented the observation that individuals expressing an intention to use prenatal DNA diagnostic services and terminate an “affected” fetus are more severely affected by their disorder than those who would not, or who were unsure about their use of molecular genetic testing.
Partial trisomy 8q. Two case reports with maternal translocation and inverted insertion: phenotype analyses and reflections on the risk
Authors: Stengel‐Rutkowski S. , Lohse K. , Herzog C. , Apacik C. , Couturier J. , Albert A. , Belohradsky B.
Published: July 2010

Partial trisomy 8qter→q23 or q24.1 has been reported in 15 literature cases. We add two further case reports here. Patient 1 inherited the derivative (2) of a balanced maternal reciprocal translocation t(2;8)(qter;q2300) after 2:2 disjunction and adjacent‐1 segregation, and is trisomic for the segment 8qter→q2300. Patient 2 inherited a recombinant (8) of a balanced maternal inverted insertion inv ins(8)(q1300;q2300q24.2) and is trisomic for the segment 8q24.2→q2300. The phenotype of both patients is described and compared to the spectrum of symptoms established from the 15 literature cases. This spectrum contains all features observed with a frequency of > = 50%. Patient 1 had 35% of the features of this spectrum; Patient 2 had 47%. The intrauterine survival probability of unbalanced offspring is assumed to be the same in both cases, as nearly the same segments are trisomic. The pedigrees indicate that the inversion carrier may have a reduced production probability of unbalanced gametes and therefore a reduced risk compared to the translocation carrier.
Clinical, cytogenetic and molecular investigations in three patients with Wolf‐Hirschhorn syndrome
Authors: Thies Ulrike , Back Elke , Wolff Gerhard , Schroeder‐Kurth Traute , Hager Hans‐Dieter , Schröder Kirsten
Published: July 2010

Clinical, cytogenetic and molecular studies were performed in three patients with Wolf‐Hirschhorn syndrome (WHS). In all cases the altered chromosome 4 appeared to be the result of a de novo deletion. Cytogenetic investigations located the breakpoint at 4p15.3 and 4p13. With cytogenetic methods it was not possible to decide whether these deletions were terminal or interstitial. DNA methods also failed to define a distal breakpoint within the 4p16.3 region which might have indicated an interstitial deletion. According to the literature, the paternal chromosome 4 is preferentially deleted in most patients with WHS. DNA analysis with polymorphic markers out of the 4p16.3 region revealed that in two of the cases reported here the deleted segment was of paternal and in one case of maternal origin.
A case of human chimerism detected by unbalanced chromosomal translocation
Authors: Nyberg R. H. , Haapala A. K. , Simola K. O. J.
Published: July 2010

Chimerism in humans is usually found only because of discrepancies in unique blood group typing or sex chromosome complements. We describe a case found because of an inherited chromosomal translocation. A female carrier of the balanced reciprocal translocation t(14;20)(q31; q13.3) had a twin pregnancy. After birth the B‐twin, a girl, was found to have the balanced translocation. The A‐twin, a severely malformed and stillborn boy, had two different karyotypes; a normal 46,XY and an unbalanced translocation derivative 46,XY, – 14, + der(14)t(14;20)(q31;q13.3). He was a dispermic chimera, formed by two fertilized oocytes.
Posterior scalp defects in Opitz syndrome. Another symptom related to a defect in midline development
Authors: Fryns J. P. , Delooz J. , van den Berghe H.
Published: July 2010

In this report we describe the presence of a large, posterior scalp defect as another, hitherto nonreported symptom related to a defect in midline development in a 1‐year‐old boy with Opitz syndrome.
Identical twins with an autosomal recessive form of spondylocostal dysostosis
Authors: Satar M. , Kozanoḡlu M. N. , Atilla L.
Published: July 2010

A form of spondylocostal dysostosis, marked by multiple vertebral clefts, costal bifurcation, and fusion was observed in identical male twins whose parents were first cousins. The lack of previous anomalies in the family, the high degree of parental inbreeding and the absence of deformities in a 3‐year‐old brother indicated an autosomal recessive mode of inheritance.
Gaudier patients with oculomotor abnormalities do not have a unique genotype
Authors: Sidransky Ellen , Tsujl Shoji , Stubblefield Barbara K. , Gurrie Jon , FitzGibbon Edfflond J. , Glnns Edward I.
Published: July 2010

Sidransky E, Tsuji S, Stubblefield BK, Currie J, FitzGibbon E, Ginns EI. Gaudier patients with oculomotor abnormalities do not have a unique genotype. Clin Genet 1992: 41: 1–5.

Sixteen non‐Ashkenazic American children with Gaucher disease who demonstrate slowing of the horizontal saccades are described. Attempts to correlate this specific clinical phenotype with a unique genotype were unsuccessful. Focusing on the three most common mutations, at least five different genotypes were present in these patients. Children with this isolated oculomotor abnormality generally had a diffusely slowed background on EEG, but an otherwise normal neurologic examination, and exhibited earlier and more severe systemic manifestations and mortality. This study emphasizes the need for careful sequential neuro‐ophthalmo‐logic examinations in Gaucher patients and the need for caution in attempting to make clinical predictions regarding the course of Gaucher disease on the basis of current DNA mutational analysis.
An HLA study in 74 Danish haemochromatosis patients and in 21 of their families
Authors: Milman Nils , Graudal Niels , Nielsen Lillian Staub , Fenger Kirsten
Published: July 2010

Milman N, Graudal N, Nielsen LS, Fenger K. An HLA study in 74 Danish haemochromatosis patients and in 21 of their families. Clin Genet 1992: 41: 6–11

HLA‐A and ‐B alleles in 74 Danish patients and 21 homozygous relatives with idiopathic haemochromatosis (IH) were compared with those in a sample of 1719 chromosomes from healthy Danish control subjects. The following alleles occurred with higher frequencies in IH compared to controls: A3: 53.6% vs. 15.1% (Pc <0.001); B7: 33.1% vs. 15.6% (Pc <0.001): B14: 6.9% vs. 3.0% (Pc >0.05); B38: 5% vs. 0.9% (Pc >0.05); B47: 4.0% vs. 0.4% (Pc >0.05). Pedigree analyses disclosed 19 different haplotypes in IH subjects, compared to 286 haplotypes in controls. The following haplotypes occurred with higher frequency in IH compared to controls: A3,B5: 10.3% vs. 0.3% (Pc <0.001); A3,B7: 25.6% vs. 6.6% (Pc= 0.001); A3,BI4: 3.4% vs. 0.6% (Pc >0.05); A3,B47: 6.9% vs. 0.2% (Pc >0.05). The major IH marker HLA‐A3 was found in 56% of the haplotypes. The patterns of HLA‐alleles associated with IH in Denmark show similarities to those in Central Europe, Australia, USA and Canada, being A3,B7 dominated and those in Central Sweden, England and Ireland, being A3, B14 dominated.
Birth prevalence studies of the Crouzon syndrome: comparison of direct and indirect methods
Authors: Cohen M. Michael , Krelborg Sven
Published: July 2010

Cohen Jr MM, Kreiborg S. Birth prevalence studies of the Crouzon syndrome: comparison of direct and indirect methods. Clin Genet 1992: 41: 12–15.

An indirect method for estimating the birth prevalence of the Crouzon syndrome is presented. The fraction of Crouzon syndrome patients in large clinical surveys of all cases of craniosynostosis is calculated and the fractional component obtained is multiplied by the known birth prevalence of craniosynostosis in general. Crouzon syndrome makes up approximately 4.8% of all cases of craniosynostosis. Using a weighted average estimate, birth prevalence was calculated to be 16.5/1 000 000. The results of the indirect method compare favorably with those obtained by the direct method. Nevertheless, because the indirect method is based on a number of assumptions that are easily violated, we cannot recommend its general use except under special circumstances.
A unique de novo interstitial deletion del(17) (q21.3q23) in a phenotypically abnormal infant
Authors: Park Jonathan P. , Moeschler John B. , Berg Susan Z. , Bauer Ranee M. , Wurster‐Hill Doris H.
Published: July 2010

Park JP, Moeschler JB, Berg SZ, Bauer RM, Wurster‐Hill DH. A unique de novo interstitial deletion del(17)(q21.3q23) in a phenotypically abnormal infant. Clin Genet 1992:41: 54–56.

We report on an infant with multiple congenital anomalies possessing a de novo, interstitially deleted no. 17 chromosome. The phenotype includes brachycephaly, club feet, delay of growth and development, and hyperte‐lorism with upslanted palpebral fissures. We are unaware of other reported cases involving such interstitial deletion of 17, or of translocations involving the breakpoint regions observed in our case.
The thymic findings in stillborns with neural tube defects
Authors: Seniz Fatma Nur
Published: July 2010

Seniz FN. The thymic findings in stillborns with neural tube defects. Clin Genet 1992: 41: 62–64.

Neural tube defects are among the most common congenital anomalies causing perinatal deaths. Other organ system anomalies may be associated with neural tube defects: for instance, various types of thymus pathology have been reported in these patients. In this study thymic changes were investigated in 30 stillborns with neural tube defects seen between January 1988 and June 1989. Thymic weights were significantly reduced in 14 cases and increased in 7. One patient had a double thymus, and in two cases no thymus tissue could be found. These findings suggest a primary developmental defect of the neural crest, affecting the orderly development of the thymus gland.
Autosomal dominant congenital cataract; linkage relations; clinical and genetic heterogeneity
Authors: Lund Allan M. , Eiberg Hans , Rosenberg Thomas , Warburg Mette
Published: July 2010

Lund AM, Eiberg H, Rosenberg T, Warburg M. Autosomal dominant cataract; linkage relations; clinical and genetic heterogeneity. Clin Genet 1992:41:65–69.

Congenital cataract is a heterogeneous disorder. Approximately one third of the cases are hereditary. A large family with autosomal dominant congenital cataract is described here. Clinical examinations showed variable expressivity, but all affected persons were eventually operated, most of them in the first or second decade of life. Linkage relations with a number of polymorphic marker systems were studied, all of them being negative. Among the 21 systems studied were Fy, HP, DI6S4 and CRYG. The present autosomal dominant congenital cataract is termed the Volkman cataract, after the ancestor in the pedigree, and is genotypically different from the Marner cataract found in another large Danish pedigree.
A new form of X‐linked, high‐frequency, sensorineural deafness
Authors: Wellesley Diana , Goldblatt Jack
Published: July 2010

Wellesley D, Goldblatt J. A new form of X‐linked, high‐frequency, sensorineural deafness. Clin Genet 1992:41:79–81.

A kindred is described in which five male members over three generations manifested a high‐frequency deafness. Their isolated sensorineural hearing loss was non‐progressive and only in the 1500–8000 Hz range. The pattern of inheritance and nature of the auditory deficit would suggest it is a previously undescribed X‐linked form of deafness.
A boy with Poland anomaly and facio‐auriculo‐vertebral dysplasia
Authors: Cobben J. M. , van Essen A. J. , McParland P. G. , Polman H. A. , ten Kate L. P.
Published: July 2010

Cobben JM, Van Essen AJ, McParland PC, Polman HA, ten Kate LP. A boy with Poland anomaly and facio‐auriculo‐vertebral dysplasia. Clin Genet 1992: 41: 105–107.

Poland anomaly and facio‐auriculo‐vertebral dysplasia are considered to be separate entities. We describe a 3‐year‐old boy with features of both Poland anomaly and facio‐auriculo‐vertebral dysplasia. This is the first report, to our knowledge, of this combination of birth defects. Possible pathogenetic implications are discussed.
Hereditary motor and sensory neuropathy type I, associated with aplasia cutis congenital possible X‐linked inheritance
Authors: Castle David , Isaacs Hyam , Ramsay Michale , Bernstein Renee
Published: July 2010

Castle D, Isaacs H, Ramsay M, Bernstein R. Hereditary motor and sensory neuropathy type I, associated with aplasia cutis congenita: possible X‐linked inheritance. Clin Genet 1992:41: 108–110.

We report a family with possible X‐linked recessive HMSN I with minor signs of the disease and abnormal sensory conduction studies evident in female carriers. There is a previously undescribed association with aplasia cutis congenita in both affected males, and a history of a severe skull defect in a third male child, who died at birth. The latter defect usually shows an autosomal dominant pattern of inheritance.
Influence of apolipoprotein B signal peptide insertion/deletion polymorphism on serum lipids and apolipoproteins in a Chinese population
Authors: Saha N. , Tay J. S. H. , Chew L. S.
Published: July 2010

Saha N, Tay JSH, Chew LS. Influence of apolipoprotein B signal peptide insertion/deletion polymorphism on serum lipids and apolipoproteins in a Chinese population. Clin Genet 1992:41: 152–156.

Insertion/deletion polymorphism of the apo B gene encoding signal peptide and its influence on serum lipids and apolipoproteins was studied in 269 Chinese of both sexes in Singapore. The frequency of the Del allele was found to be 0.20, which is significantly lower than that in Caucasians (France) (0.34). The distribution of genotypes of ins/del polymorphism was at Hardy‐Weinberg equilibrium in this population. There was an excess of individuals with the deletion allele in hypercholesterolemic subjects compared to those with normal cholesterol levels (P<0.05). All the lipid and apolipoprotein values were regressed for age, sex and BMI by multiple regression analysis. Individuals with one or two del alleles had significantly higher levels of serum total cholesterol (248.8± 13.0 and 255.4±20.4 mg/dl, respectively) compared to those in individuals with only the Ins allele (218.4 ± 7.8 mg/dl) (P<0.05). Serum LDL cholesterol level was also significantly higher in individuals with del allele (173.4 ± 11.7 mg/dl) compared to that in those without the del allele (141.1 +7.4 mg/dl) (P=0.02). The percentages of sample variance of different lipid traits explained by apo B signal peptide polymorphism were estimated by analysis of variance (ANOVA) with sex, age and BMI as covariates. 2.3% of variability of serum total cholesterol (F = 3.27, P=0.040) and 2.8% of LDL cholesterol (F = 3.87, P=0.023) could be explained by the ins/del polymorphism of the apo B signal peptide gene.
Detection of subtle reciprocal translocations by fluorescence in situ hybridization
Authors: Speleman Frank , van Roy Nadine , Wlegant Joop , Verschraegen‐Spae Marie Rose , Benoit Yves , Govaert Paul , Goossens Linde , Leroy Jules G.
Published: July 2010

Speleman F, Van Roy N, Wiegant J, Verschraegen‐Spae MR, Benoit Y, Govaert P, Goossens L, Leroy JG. Detection of subtle reciprocal translocations by fluorescence in situ hybridization. Clin Genet 1992:41: 169–174.

Three different subtle reciprocal translocations were detected on long, well‐banded chromosomes. The same translocations were examined using fluorescence in situ hybridization (FISH) with chromosome‐specific libraries and unique DNA sequences. Our findings show that FISH allows rapid and unequivocal detection and characterization of this type of chromosome rearrangement. This approach is especially useful for prenatal diagnosis when one of the parents is a balanced carrier of such small fragment translocations.
Familial occurrence of ring chromosome 15
Authors: Horigome Y. , Kondo I. , Kuwajima K. , Suzuki T.
Published: July 2010

Horigome Y, Kondo I, Kuwajima K, Suzuki T. Familial occurrence of ring chromosome 15. Clin Genet 1992: 41: 178–180.

We present a family with the ring 15 chromosome (r(15)) syndrome in a 2‐year‐old infant and his mother. Both had the common clinical manifestations reported in previous cases with r(15), including severe short stature, microcephaly, triangular face, and mild mental retardation. The family also had a normal son. Although males with r(15) syndrome usually seem to be infertile, female r(15) patients are likely to be fertile and their reproductivity may be influenced by severe growth retardation.
Concomitant occurrence of mucopolysaccharidosis IIIB and Glanzmann's thrombasthenia. Further evidence of a hyperactive α‐N‐acetylglucosaminidase‐producing allele
Authors: Pande Helens , Chester Alan , Lia Halldis , Tharsby Erik , Stormorken Helge
Published: July 2010

A daughter of first cousins had two extremely rare, recessive disorders: thrombasthenia (Glanzmann's disease, glycoprotein IIb/IIIa deficiency) and mucopolysaccharidosis IIIB, (Sanfilippo B syndrome, α‐N‐acetylglu‐cosaminidase (NAG) deficiency). Normal α‐N‐acetylglucosaminidase activity was observed in two obligate heterozygotes (the proband's father and her maternal grandmother), suggesting that in addition to the normal and defective alleles, a third, hyperactive allele is also present in this family. Such a hyperactive allele seems to be quite prevalent in our area, and makes the biochemical identification of heterozygotes impossible if no extensive family surveys provide additional clues. There was no linkage between the two diseases, nor between any of them and several blood‐groups and HLA‐antigens tested for.
Dominantly inherited microcephaly, short stature and normal intelligence
Authors: Hannekam Raoul C. M. , van Rhijn Aat , Hannekam F. A. M.
Published: July 2010

A large family is reported in which microcephaly and short stature is segregating as a probably autosomal dominantly inherited trait. Some affected members also show a delayed onset of puberty. No other clinical or radiological symptoms are present, and psychomotor development is normal. This short report confirms an earlier description of a similar family by Burton in 1981.
Deletions, duplications and novel restriction fragment length polymorphism in Duchenne and Becker muscular dystrophies
Authors: Lau Y. L. , Srlvastava G. , Wong V. , Liu Y. T. , He F. C. S. , Yeung C. Y.
Published: July 2010

To determine the mutations of Southern Chinese with Duchenne and Becker muscular dystrophies (DMD, BMD), we analysed 28 DMD and BMD patients in 24 unrelated families for intragenic deletions and duplications by using cDNA probes covering the entire 14 kb of the dystro‐phin gene. Deletions were detected in nine unrelated patients (seven patients by probe 8 and two by probe 2b‐3). Gene duplications were detected by probe l‐2a in two patients with the duplication bands confirmed in both Hind III and Bgl II digests and by densitometry. A third patient was found to have a junction fragment with Bgl II and a duplication band with Hind III by probe 5b‐7. Therefore 50% of the 24 unrelated families were found to have either deletions or duplications. A previously undescri‐bed restriction fragment length polymorphism (RFLP) was found in one family with probe 5b‐7 in Bgl II digests which was found to segregate with the disease phenotype. This new RFLP was not detected in over 70 unrelated X chromosomes we have examined so far, and appeared to be “private” for this family. The presence of this new restriction site may or may not be the mutation responsible for the disease phenotype.
On planting alfalfa and growing orchids: the cloning of the gene causing Huntington disease
Authors: Hayden Michael R.
Published: July 2010

Hayden MR. On planting alfalfa and growing orchids: the cloning of the gene causing Huntington disease.

Clin Genet 1993: 43: 217–222. © Munksgaard, 1993
The hand‐foot‐genital syndrome: on the variable expression in affected males
Authors: Fryns J. P. , Vogels A. , Decock P. , van den Berghe H.
Published: July 2010

Fryns JP, Vogels A, Decock P, Van den Berghe H. The hand‐foot‐genital syndrome: on the variable expression in affected males.

Clin Genet 1993: 43: 232–234. © Munksgaard, 1993

In this report we document male‐to‐male transmission in the hand‐foot‐genital syndrome. An affected father transmitted the syndrome to his three sons. A grade IV hypospadias, which was the most severe genital anomaly in affected males, was present in the youngest, moderately mentally retarded microcephalic male sibling.
Chromosome painting using FISH (fluorescence in situ hybridization) with chromosome‐6‐specific library demonstrates the origin of a de novo 6q+ marker chromosome
Authors: Brendum‐Nielsen Karen , Bajalica Svetlana , Wulff Karl , Wikkelsen Margareta
Published: July 2010

Brøndum‐Nielsen K, Bajalica S, Wulff K, Mikkelsen M. Chromosome painting using FISH (fluorescence in situ hybridization) with chromosome‐6‐specific library demonstrates the origin of a de novo 6q+ marker chromosome.

Clin Genet 1993: 43: 235–239. © Munksgaard, 1993

We report the application of chromosome painting using FISH (fluorescence in situ hybridization) to demonstrate the origin of a de novo 6q + marker chromosome. A girl with a mental retardation/multiple malformation syndrome was shown to have the karyotype 46,XX, 6q+. Banding analysis could not determine the origin of the extra chromosomal material. Using FISH with a chromosome‐6‐specific library we showed that the marker chromosome was completely painted, indicating an origin from chromosome 6. The child's phenotype was compared with previously reported cases with partial chromosome 6 trisomy. A clinically recognized syndrome emerged, although she apparently also demonstrated novel features.
Germinal mosaicism in a Duchenne muscular dystrophy family: implications for genetic counselling
Authors: Melis Maria Antonietta , Cau Milena , Congiu Rita , Puddu Rosalha , Muntoni Francesco , Cao Antonio
Published: July 2010

Melis MA, Cau M. Congiu R, Puddu R, Muntoni F, Cao A. Germinal mosaicism in a Duchenne muscular dystrophy family: implications for genetic counselling.

Clin Genet 1993: 43: 247–249. © Munksgaard, 1993

In this study we describe a three‐generation family in which two siblings were affected by Duchenne muscular dystrophy (DMD). Immunohisto‐chemical analysis of muscle dystrophin and haplotype analysis of the DMD locus revealed that the X chromosome carrying the DMD gene was transmitted from the healthy maternal grandfather to his three daughters. including the proband's mother. These findings indicate that the grandfather was a germinal mosaic for the DMD gene. The definition of the carrier status in two possible carriers led us to give accurate genetic counselling and to prevent the birth of an affected boy. The results of this study demonstrate the usefulness of haplotype analysis and immuno‐histochemical muscle dystrophin studies to detect hidden germinal mosaicism and to improve genetic counselling.
Linkage analysis‐in a family with complete type congenital stationary night blindness with and without myopia
Authors: Dry K. L. , van Dorp D. B. , Aldred M. A. , Brown J. , Hardwick L. J. , Wright A. F.
Published: July 2010

Dry KL, Van Dorp DB, Aldred MA, Brown J, Hardwick LJ, Wright AF. Linkage analysis in a family with complete type congenital stationary night blindness with and without myopia.

Clin Genet 1993: 43: 250–254. © Munksgaard, 1993

A family is described with X‐linked congenital stationary night blindness of the complete type (CSNB1) in which clinical variation between affected males resulted in diagnostic difficulties. In two affected male cousins, one had congenital nystagmus and myopia, while the other was initially thought to have retinitis pigmentosa with optic atrophy and was hyperopic The diagnosis of X‐linked congenital stationary night blindness was established by clinical, psychophysical and electrophysiological criteria, and DNA markers flanking the CSNB1 locus were analysed in the family. The results show that both affected males have inherited the same haplotype from their carrier mothers, excluding the possibility that a myopia gene in linkage disequilibrium with CSNB1 has recombined with this locus.
Satellite polymorphism or Y/autosome translocation?
Authors: Coll M. D. , Clusellas N. , Grao P. , Gean E. , Egozcue J.
Published: July 2010

Clin Genet 1993: 43: 271–272. © Munksgaard, 1993
Familial bilateral antecubital pterygia with severe renal involvement in nail‐patella syndrome
Authors: Rizzo R. , Pavone L. , Micali G. , Hall J. G.
Published: July 2010

Rizzo R, Pavone L, Micali G, Hall JG. Familial bilateral antecubital pterygia with severe renal involvement in nail‐patella syndrome.

Clin Genet 1993: 44: 1–7. © Munksgaard, 1993

A family in whom several members are affected with nail‐patella dysplasia is reported because of severe renal involvement and bilateral antecubital pterygia. The family presented as arthrogryposis because of the elbow contractures.
Frequency of the ΔF508 and exon 11 mutations in Norwegian cystic fibrosis patients
Authors: Eiklid Kristin , Tranebjærg Lisbeth , Eiken Hans G. , Pedersen Jan C. , Michalsen Helge , Fluge Gjermund , Schwartz Marianne , Nilsen Bjørn R. , Bolle Roald , Skyberg Dag , Boman Helge , Berg Kare
Published: July 2010

Eiklid K, Tranebjærg L, Eiken HG, Pedersen JC, Michalsen H, Fluge G, Schwartz M, Nilsen BR, Bolle R, Skyberg D, Boman H, Berg K. Frequency of the ΔF508 and exon 11 mutations in Norwegian cystic fibrosis patients.

Clin Genet 1993: 44: 12–14. © Munksgaard, 1993

We have searched for the ΔF508 mutation in 77 Norwegian cystic fibrosis patients. Of the 154 chromosomes tested, 93 (60%) carried the ΔF508 mutation. Haplotypes at the D7S23 locus (KM19 and XV2C markers) were determined. Of 81 chromosomes with the F508 mutation, the B haplotype was found on 77. We found three patients with the G551D and one patient with the R553X mutation in exon 11 of the CFTR locus.
Phenotypic intrafamilial heterogeneity in cystic fibrosis
Authors: Borgo G. , Cabrini G. , Mastella G. , Ronchetto P. , Devoto M. , Romeo G.
Published: July 2010

Clin Genet 1993: 44: 48–49. © Munksgaard, 1993
The breakpoints of the EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) confirmed to 7q11.21 and 9p12 by fluorescence in situ hybridization
Authors: Fukushima Yoshimitsu , Ohashi Hirofumi , Hasegawa Tomonobu
Published: July 2010

Clin Genet 1993: 44: 50. © Munksgaard, 1993
Association of Shokeir syndrome (congenital universal alopecia, epilepsy, mental subnormality and pyorrhea) and giant pigmented nevus
Authors: Timár László , Czeizel Andrew E. , Koszó Péter
Published: July 2010

Timár L, Czeizel AE, Koszó P. Association of Shokeir syndrome (congenital universal alopecia, epilepsy, mental subnormality and pyorrhea) and giant pigmented nevus.

Clin Genet 1993: 44: 76–78. © Munksgaard, 1993

The second case of Shokeir syndrome (congenital total permanent alopecia, psychomotor epilepsy, mental retardation and pyorrhea) is described in a Hungarian boy. This syndrome was associated with a giant pigmented nevus in this case.
Effect of the fragile X anomaly on body proportions estimated by pedigree analysis
Authors: Loesch Danuta Z. , Sampson Mark L.
Published: July 2010

Loesch DZ, Sampson ML. Effect of the fragile X anomaly on body proportions estimated by pedigree analysis.

Clin Genet 1993: 44: 82–88. © Munksgaard, 1993

The purpose of this study was to determine the effect of the fragile X syndrome on limb (upper limb length) and facial (ear length) measurements in relation to body height, which was considered as a covariate. The analysis was performed in 52 fragile X Caucasian families, including affected individuals as well as their normal relatives. The maximum likelihood analysis of complex pedigrees, under the assumption of multivariate normality, was used to select the best genetic model and to estimate model parameters. This method allowed us to test various assumptions concerning the effect of normal hereditary variation, as well as of genetic anomaly and other relevant factors, in the mean and variance of a quantitative trait, and to obtain the maximum likelihood parameters for these effects. The results demonstrated that, if the family factor is accounted for in a model, the fragile X condition affects growth of both upper limb length and ear length, disproportionately to body height.
Application of molecular and cytogenetic techniques to the detection of a de novo unbalanced t(11q;21q) in a patient previously diagnosed as having monosomy 21
Authors: Hertz Birgitte , Brandt Carsten A. , Petersen Michael B. , Pedersen Søren , König Ulrich , Strømkjær Helle , Jensen Peter K. A.
Published: July 2010

Hertz B, Brandt CA, Petersen MB, Pedersen S, König U, Strømkjær H, Jensen PKA. Application of molecular and cytogenetic techniques to the detection of a de novo unbalanced t(11q;21q) in a patient previously diagnosed as having monosomy 21.

Clin Genet 1993: 44: 89–94. © Munksgaard, 1993

The occurrence of complete autosomal monosomy in man is extremely rare and generally considered to be incompatible with life. Since the introduction of banding techniques in human cytogenetics, several cases of presumptive monosomy for chromosome 21 have nevertheless been reported. However, it has been suggested that most, if not all, of these cases may represent unbalanced translocations or other structural aberrations resulting in only partial monosomy 21. Here we describe a patient in whom full monosomy 21 was initially diagnosed by routine karyotyping. Re‐examination with a combination of high resolution banding technique, chromosome painting and DNA polymorphism analysis demonstrated the presence of an unbalanced translocation between the long arms of chromosome 11 and 21, respectively. Consequently, the case was re‐classified as a partial monosomy for the proximal long arm of chromosome 21.
Prenatal screening for cystic fibrosis: attitudes and responses of participants
Authors: Mennie Moira , Compton Mary , Gilfillan Annette , Axton R. A. , Liston W. A. , Pullen I. , Whyte Dorothy , Brock D. J. H.
Published: July 2010

Mennie M, Compton M, Gilfillan A, Axton RA, Liston WA, Pullen I, Whyte D, Brock DJH. Prenatal screening for cystic fibrosis: attitudes and responses of participants.

Clin Genet 1993: 44: 102–106. © Munksgaard, 1993

A screening programme to detect cystic fibrosis heterozygotes has been running in the antenatal climes of a major Edinburgh maternity hospital for more than 2 years. A questionnaire was used to assess participants' knowledge of the genetics of the disorder and their attitudes to being screened. The respondents were 64 female heterozygotes and 63 of their non‐heterozygous male partners, 101 female controls and 100 male controls. Although the two groups of controls received far less direct information than the carriers and their partners, all four groups were well informed about the genetics of cystic fibrosis and the significance of being a gene carrier. A majority of each group felt that adequate information had been given in the information leaflet, that they understood the purpose of screening and that they were glad to have participated. There was a consensus that CF carrier testing should be routinely offered to pregnant women, and also that it should be available in family planning clinics and GP health centres, but not in schools.
Bilateral vocal cord paralysis in Williams syndrome
Authors: Stewart F. J. , Dalzell M. , McReid M. , Cinnamond M. J.
Published: July 2010

Stewart FJ, Dalzell M, McReid M, Cinnamond MJ. Bilateral vocal cord paralysis in Williams syndrome.

Clin Genet 1993: 44: 164–165. © Munksgaard, 1993

Williams syndrome was first described in 1961 (Williams et al. 1961) and is a well‐recognised clinical syndrome characterised by growth deficiency, learning difficulties and a typical facies. We describe a 9‐year‐old girl with classical features of Williams syndrome who presented with acute vocal cord paralysis for which no other cause was found.
Prenatal diagnosis of fragile X syndrome by direct detection of the dynamic mutation due to an unstable DNA sequence
Authors: Yamauchi Masatake , Nagata Shin , Seki Naohiko , Toyama Yoshiro , Harada Naoki , Niikawa Norio , Masuno Ichiro , Kajii Tadashi , Hori Tada‐aki
Published: July 2010

Yamauchi M, Nagata S, Seki N, Toyama Y, Harada N, Niikawa N, Masuno I, Kajii T, Hori T. Prenatal diagnosis of fragile X syndrome by direct detection of the dynamic mutation due to an unstable DNA sequence.

Clin Genet 1993: 44: 169–172. © Munksgaard, 1993

The fragile X syndrome is the most common familial form of mental retardation. The mutation causing the syndrome is dynamic mutation due to an unstable DNA (CCG)n repeat localized at Xq27.3. We have previously reported a PCR procedure to prepare a diagnostic probe, pPCRfx1, which can be used to determine the genotype of fragile X mutation individuals by Southern blot analysis. In the present study, pPCRfx1 was applied to the prenatal diagnosis, using chorionic villus cells, of a fetus which was at risk of having fragile X syndrome. In the PstI assay, the Southern blot showed the typical pattern of a female carrier with the full mutation. Analysis of the DNA methylation patterns by EcoRI + EagI assay showed that the EagI restriction site was not methylated on the mutated X chromosome of chorionic villi, but the sites were totally methylated in the brain and other tissues of the fetus. Thus the fetus was diagnosed to be a heterozygous female carrier of the dynamic mutation involved in the fragile X syndrome.
Haplotype analysis at the low density lipoprotein receptor locus in normal and familial hypercholesterolemia Norwegian subjects
Authors: Rødningen Olaug K. , Leren Trond P. , Røsby Oddveig , Tonstad Serena , Ose Leiv , Berg Kare
Published: July 2010

Rødningen OK, Leren TP, Røsby O, Tonstad S, Ose L, Berg K. Haplotype analysis at the low density lipoprotein receptor locus in normal and familial hypercholesterolemia Norwegian subjects.

Clin Genet 1993: 44: 214–220. © Munksgaard, 1993

We have performed haplotype analysis at the low density lipoprotein receptor (LDLR) locus in order to investigate the molecular genetics of familial hypercholesterolemia (FH) in Norway. Haplotypes were constructed using 7 restriction fragment length polymorphisms (RFLPs) in 194 subjects from 48 unrelated Norwegian FH families. Hypercholesterolemia co‐segregated with haplotypes at the LDLR locus in all 48 families. Unambiguous haplotypes could be established for 190 independent chromosomes from 51 FH heterozygotes and 44 healthy normal subjects. A total of 20 different haplotypes was found. The most frequent haplotype was haplotype 3, which accounted for 32.4% or 43.1% of the normal and defective haplotypes, respectively. Haplotype 2 was significantly more frequent among the defective alleles than among the normal alleles (33.3% and 5.8%, respectively, p<0.0001). Thus, haplotypes 2 and 3 accounted for 76.4% of the defective haplotypes. More data are needed to determine the possible existence of founder genes in the Norwegian population. Haplotypes 1, 2, 3, 5 and 8 accounted for 88.2% of the normal haplotypes. Based upon the cumulative heterozygosity index, the SphI, NcoI and 3′ ApaLI RFLPs are the most informative markers in the Norwegian population.
Suggestion of linkage between manic‐depressive illness and the enzyme phosphoglycolate phosphatase (PGP) on chromosome 16p
Authors: Eiberg H. , Ewald H. , Mors O.
Published: July 2010

Eiberg H, Ewald H, Mors O. Suggestion of linkage between manic‐depressive illness and the enzyme phosphoglycolate phosphatase (PGP) on chromosome 16p. Clin Genet 1993: 44: 254–257. © Munksgaard, 1993

Two large Danish pedigrees with manic‐depressive illness (MDI) were ascertained through bipolar probands. The pedigrees include bipolar as well as unipolar cases. An autosomal dominant mode of inheritance with incomplete penetrance was assumed. Linkage relationships between MDI and 37 autosomal serum, enzyme and blood group markers were investigated. For phosphoglycolate phosphatase, a maximum lod score of 2.20 at 0% recombination was found for the largest family. The other family was not informative. This may suggest assignment of a major gene for MDI to chromosome 16p13.
Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin expression
Authors: Dean John C. S. , Gray E. S. , Stewart K. N. , Brown T. , Lloyd D. J. , Smith N. C. , Pope F. M.
Published: July 2010

Dean JCS, Gray ES, Stewart KN, Brown T, Lloyd DJ, Smith NC, Pope FM. Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin expression.

Clin Genet 1993: 44: 287–291. © Munksgaard, 1993

Clinical features and histological findings in two sibs who died from restrictive dermopathy in the neonatal period are described. Fibroblasts cultured from a skin biopsy from the second sib and fibroblasts from normal neonatal skin were studied using monoclonal antibodies to visualise integrin subunits by immunocytochemistry. Restrictive dermopathy fibroblasts displayed increased expression of the alpha‐1 and alpha‐2 subunits of integrin, those responsible for collagen binding. The increase was not matrix dependent. Integrins may play an important role in tissue differentiation, and our findings support the hypothesis that restrictive dermopathy is a disorder of skin differentiation.
A mild form of mucolipidosis type III in four Baluch siblings
Authors: Ward Chandra , Singh Rashmi , Slade Christina , Fensom A. H. , Fahmy A. , Semrin A. , Sjövall A. , Talat A. , Hasilik A. , Klein I. , Benson P. F.
Published: July 2010

Ward C, Singh R, Slade C, Fensom AH, Fahmy A, Semrin A, Sjövall A, Talat A, Hasilik A, Klein I, Benson PF. A mild form of mucolipidosis type III in four Baluch siblings.

Four Baluch siblings with mucolipidosis type III (pseudo‐Hurler polydystrophy) are described. The patients had features commonly found in mucolipidosis III, including claw hands, joint stiffness, aortic valve involvement and radiological dysostosis multiplex. However, intelligence was normal, there were no eye abnormalities on slit‐lamp examination and skin elasticity was normal. Many lysosomal enzymes were elevated in serum and diminished in cultured fibroblasts, although the findings for β‐galac‐tosidase were atypical. Assays for the two enzymes involved in formation of the phosphomannose recognition marker revealed normal activity of the phosphotransferase with α‐methylmannoside as an acceptor, and normal activity of the phosphodiester glycosidase. Metabolic labelling of fibroblasts with 32P followed by immunoprecipitation of cathepsin D, electrophoresis and fluorography showed that this enzyme was not labelled in the patients' cells, although some label was detected in the secreted precursor polypeptide. The data are consistent with the assumption that activity of the phosphotransferase is low towards lysosomal enzymes as substrates, and that the patients belong to complementation group C.