bluuebunny/crossref_metadata_2025 huggingface dataset:
Fragile sites and chromosome breakpoints in constitutional rearrangements II. Spontaneous abortions, stillbirths and newborns
Authors: Hecht Frederick , Hecht Barbara K.
Published: July 2010

Certain fragile sites may possibly predispose to chromosome breakage and rearrangements in meiosis. To test this hypothesis, we examined 894 breakpoints found in spontaneous abortions, stillbirths and livebirths of which 165 (18.5%) were in bands with fragile sites. Compared to an expectation of 98 (11%), there was a significant excess of breakpoints in fragile site bands (P<0,001). Together with data from amniocenteses, there is now evidence suggesting that certain fragile sites may be prone to fragility in meiosis.
Ankylosing spondylitis is part of a multifactorial syndrome: hereditary multifocal relapsing inflammation (HEMRI)
Authors: Møllerand Pål , Berg Kare
Published: July 2010

Complex associations between the different subgroups of seronegative arthritis, acute anterior uveitis, psoriasis and inflammatory bowel disease were found in a series of patients and relatives. Different HLA‐B antigens were associated with different clinical signs. The results indicated the existence of a multigenic syndrome whose main clinical manifestations are relapsing innflammations at various sites. The genetic factors appeared to be 1) HLA‐B27 associated disease susceptibility, 2) predisposition to psoriatic arthropathy, 3) predisposition to early onset familial psoriasis and, 4) a probable predisposition to inflammatory bowel disease and its associated arthropathy. The results indicated that the different genetic factors may interact and influence each other's penetrance and expression.
Cholesterol ester storage disease in an adult presenting with sea‐blue histiocytosis
Authors: Besley G. T. N. , Broadhead D. M. , Lawlor Emer , McCann S. R. , Dempsey J. D. , Drury M. I. , Crowe J.
Published: July 2010

An adult patient is described with hepatomegaly and sea‐blue histiocytes in the bone marrow. A diagnosis of cholesterol ester storage disease was established following enzyme and lipid analyses on liver biopsy and cultured skin fibroblasts. Acid esterase activity was deficient (approx. 5% of controls) in liver and fibroblasts using [14C]‐triolein or 4‐methylumbelliferyl palmitate as substrates. Cholesterol ester levels were raised about 70‐fold in liver, whereas triglyceride levels were only marginally raised. Marked accumulation of cholesterol esters was also demonstrated in cultured fibroblasts. Clinically, the patient responded favourably to phenobarbitone treatment. However, this was not reflected in liver acid esterase or lipid levels.
Familial partial monosomy 5p and trisomy 5q; three cases due to paternal pericentric inversion 5 (p151q333)
Authors: Beemer F. A. , France H. F. de , Rosina‐Angelista I. J. M. , Gerards L. J. , Cats B. P. , Guyt R.
Published: July 2010

A family is described in which the mother's 9 pregnancies ended in the birth of 2 healthy girls, 4 spontaneous abortions and 3 infants with multiple congenital malformations as bird‐headed appearance, pre‐ and postnatal growth deficiency, microcephaly, micrognathia with small mouth and cat‐like cry. Two of the three affected sibs had complex cardiac malformations incompatible with life; the third had a bicuspid aortic valve. Chromosomal investigation revealed an abnormal karyotype: 46,XX, rec(S),dupq, inv(5)(p151q333)pat, leading to a partial monosomy 5p and partial trisomy 5q. A large pericentric inversion of chromosome 5 was found in the father: 46,XY, inv(5)(p151q333) as well as in the firstborn healthy female sib. The clinical features partly fit the partial monosomy 5p as well as the partial trisomy 5q syndrome.
Biochemical studies in Niemann‐Pick disease. III: In vitro and in vivo assays of sphingomyelin degradation in cultured skin fibroblasts and amniotic fluid cells for the diagnosis of the various forms of the disease
Authors: Vanier Marie T. , Rousson Robert , Garcia Isabelle , Bailloud Geneviève , Juge Marie‐Christine , Revol A. , Louisot P.
Published: July 2010

Sphingomyelinase activities were assayed in vitro in cultured skin fibroblasts of 61 patients with Niemann‐Pick disease (NPD). Residual activities found in type A and B were 1% and 4%, respectively, of the mean control values, i.e. significantly higher in type B. In 27 cases with NPD type C, the mean activity was 42% of that in controls, with residual activities ranging from 15% up to normal. Fifteen pregnancies at risk for NPD type A and B were monitored; 4 affected foetuses were found.

The uptake of exogeneously added radiolabeled sphingomyelin by cultured cells and metabolism of the choline moiety of this lipid were studied in 35 patients with NPD and 14 controls. No difference of uptake between normal and mutant cells was observed. Normally, 77 ± 5% of the radioactivity taken up was converted to phosphatidylcholine after 18 h incubation, compared to 5±2% (n = 7) in NPD type A. A substantially greater hydrolysis (31 ±12%; n = 8) occurred in NPD type B, and the test allowed complete discrimination between these two types. In NPD type C, 16 patients showed an abnormally low rate of intracellular sphingomyelin degradation (48 ± 5%) while 4 others were not distinguishable from controls. There was a correlation (r = 0.76) between the results of the in vitro and in vivo assays, but also between the severity of the clinical symptoms and the impairment in sphingomyelin degradation. For the diagnosis of NPD type C, the in vivo test gave more reproducible and more clearcut results than the in vitro assay.
Late onset GM2 gangliosidosis: an α‐locus genetic compound with near normal hexosaminidase activity
Authors: Charrow Joel , Inui Koji , Wenger David A.
Published: July 2010

A non‐Jewish child with late onset GM2 gangliosidosis is described. Tissues from the patient had near normal hexosaminidase A (hex A) activity using 4‐methylumbelliferyl‐2‐acetamido‐2‐deoxy‐β‐D‐glucopyranoside (MU‐glcNAc) as substrate, and deficient activity when assayed with the 6‐sulfate derivative of MU‐glcNAc (MU‐glcNAcS) or GM2 in the presence of activator. We present evidence that this patient is a genetic compound for different oc‐subunit mutations. The father's tissues have hex A activity in the heterozygote range when assayed with MU‐glcNAcS, but normal activity using MU‐glcNAc; the mother's tissues have activities toward both substrates in the heterozygote range. These results emphasize the pitfalls of using only MU‐glcNAc for the diagnosis of unusual variants of GM2 gangliosidosis.
Trisomy 10 mosaicism in a newborn boy; delineation of the syndrome
Authors: France H. F. de , Beemer F. A. , Senders R. Ch. , Schaminee‐Main S. C. E.
Published: July 2010

The fifth case of trisomy 10 mosaicism is presented. Only in cultured fibroblasts this mosaicism was found, while peripheral lymphocytes revealed a normal karyotype. In comparison with the literature, trisomy 10 mosaicism syndrome is further delineated compromising of failure to thrive, high forehead, hypertelorism, mongoloid eye slant, blepharophimosis, dysplastic, large ears, retrognathia, long slender trunk, marked plantar and palmar furrows, cardiopathy and early death.
Dermatoglyphic findings in patients with fragile X‐chromosome
Authors: Hirth L. , Singh S. , Schilling S. , Müller E. , Goedde H. W.
Published: July 2010

Finger‐ and palmar prints of hemi‐ and heterozygote fragile X‐patients with mental retardation (10 males and 5 females) were compared to dermatoglyphic findings in 20 mentally retarded patients (10 males and 10 females) without fragile X and to 200 healthy unrelated persons (100 males and 100 females).

Characteristic whorls and double‐loops with high ridge‐counts on finger‐tips and a pronounced transversal course of palmar ridges were restricted to males with fragile X. Female carriers of fragile X showed, corresponding to male patients, some abnormalities of the digital‐and palmar ridge‐pattern. Contrary to males, in carriers as well as in mentally retarded females without fragile X, fingerprints with low ridge‐counts were found.

Common to all mentally retarded patients, but more pronounced in males with fragile X, abnormal palmar creases and hand‐measurements were observed. These findings probably are related to prenatal retarded growth of the length of the palma and of the middle‐finger.
Oral and dental development in X chromosome aneuploidy
Authors: Farge P. , Dallaire L. , Albert G. , Melanĉon S. B. , Potter M. , Leboeuf G.
Published: July 2010

Though frequently noted, orofacial anomalies in poly X syndromes have been seldom reviewed. In a study of patients with an X chromosome aneuploidy (XXXXX, XXXX, XXXXY, XXX Y) the following facial and dental defects were found to be characteristic features of these syndromes: mainly bifid uvula and macroglossia, enamel defects, dental taurodontism and abnormal roots. These observations are discussed in the light of the possible role of X‐linked genes.
Decreased scattering coefficient of blue sclerae
Authors: Lanting Peter J. H. , Borsboom Peter C. F. , Meerman Gerard J. te , Kate Leo P. ten
Published: July 2010

The optical scattering properties of blue and normal sclerae were studied with a fiber optic scattering monitor. The scattering was clearly reduced in two osteogenesis imperfecta patients with blue sclerae, and low normal in one osteogenesis imperfecta patient without blue sclerae.
Supraumbilical midabdominal raphe and facial cavernous hemangiomas
Authors: Igarashi M. , Uchida H. , Kajii T.
Published: July 2010

A 7‐week‐old Japanese female infant with supraumbilical midabdominal raphe and cavernous hemangiomas of the face is described. The combination of malformations in the infant, together with that in two infants previously reported from Germany, constitutes a clinical entity.
The incidence of Down syndrome in northern Finland with special reference to maternal age
Authors: Leisti J. , Vahtola L. , Linna S.‐L. , Herva R. , Koskela S.‐L. , Vitali M.
Published: July 2010

The incidence of live‐born children with Down syndrome was found to be 1.73/1000 (1:578) in northern Finland over the years 1965 to 1979. Despite a marked reduction in the proportion of older mothers, no significant change in the incidence was observed. Instead, an age‐specific rise in the incidence for mothers aged 25 to 29 years could be shown during the last five‐year period in years 1975 to 1979.
Inherited tandem duplication dup(X) (q131‐q212) in a male proband
Authors: Vejerslev Lars O. , Rix Mariane , Jespersen Birthe
Published: July 2010

A tandem duplication dup(X) (q131–q212) has been diagnosed neonatally because of the peculiar appearance. Family investigation demonstrated that the duplication has segregated through phenotypically normal female carriers for at least three generations. Inactivation studies showed that the aberrant X was preferentially late replicating. The difficulties related to prenatal diagnosis of minor X chromosome aberrations in males are discussed.
X‐linked Ehlers‐Danlos syndrome type V; the next generation
Authors: Beighton Peter , Curtis Diana
Published: July 2010

Two English families with the X‐linked form (Type V) of the Ehlers‐Danlos syndrome (EDS) who were investigated almost 20 years ago have been re‐studied. In one family, the potentially heterozygous sister of 3 affected brothers had born two sons, of whom one has EDS. The 3 brothers had all procreated, producing a total of 2 sons and 3 daughters, all of whom are clinically normal. These pedigree data provide further evidence to support the syndromic identity and X‐linked mode of inheritance of this form of the EDS.

In the second family, two affected brothers had both procreated; one had produced three normal offspring, while the other had a son with soft extensible skin and a daughter with articular hypermobility. The syndromic status of this kindred is uncertain.

Serum copper and ceruloplasmin concentrations in affected males and obligate carrier females in both families were normal. Cytogenetic investigations, including high resolution banding, yielded normal results.
Unbalanced karyotype with normal phenotype in a family with translocation (8;13) (p21;q22)
Authors: Bröcker‐Vriends A. H. J. T. , Kamp J. J. P. van de , Geraedts J. P. M. , Bos S. E. , Nijenhuis Th. A.
Published: July 2010

We describe a family with translocation (8; 13) (p21;q22), in which both unbalanced products of adjacent‐1 segregation occurred. Two members of the family have partial trisomy 8p with partial monosomy 13q; two others have partial monosomy 8p with partial trisomy 13q. The latter are both phenotypically normal, which is a highly unusual observation. One of these is, in addition, a carrier of a de novo balanced translocation between chromosomes 2 and 19. The risk for unbalanced progeny is discussed.
Autosomal dominant transmission of ankylosed teeth, abnormalities of the jaws, and clinodactyly
Authors: Pelias M. Z. , Kinnebrew M. C.
Published: July 2010

Twelve persons in four generations of a rural family of mixed racial ancestry exhibited ankylosed teeth, bilateral clinodactyly of the fifth fingers, and abnormalities of the jaws. This previously undescribed association of dental, digital, and skeletal anomalies appears to be transmitted in an autosomal dominant manner in this family. Clinical manifestations in the examined persons and an extended family history are described in detail. Previous studies of apparently hereditary dental ankylosis are similarly discussed.
Heterogeneity of Kallmann's syndrome
Authors: Hermanussen M. , Sippell W. G.
Published: July 2010

Kallmann's syndrome is a rare condition defined as a combination of hypogonadotropic hypogonadism and anosmia. The present study shows two genealogical tables. In the first family six male members in four generations had Kallmann's syndrome. All carrier females seemed to have normal fertility and normal olfactorial function. X‐linked recessive or — less probable — dominant sex linked inheritance was considered to be most probable. Renal malformation was discovered in one and was excluded in two affected members. In the second family only one affected female was discovered. She had a monozygotic twin sister with normal pubertal development, but also total anosmia. Four individuals with anosmia alone were found in this family, but no further cases of hypogonadism. The possibility of an acquired hypothalamic insufficiency on the basis of hereditary anosmia is discussed.
Expression of X‐linked hypohidrotic ectodermal dysplasia in six males and in their mothers
Authors: Söderholm Anna‐Lisa , Kaitila Ilkka
Published: July 2010

Six male patients with confirmed X‐linked hypohidrotic ectodermal dysplasia and their mothers were studied to determine the variation of expressivity in patients and heterozygotes, major problems of the patients, and to find a clue to pathogenesis.

The number of teeth, conic in shape, in patients varied from none to 14. In addition to hypohidrosis and hypotrichosis, dry skin, reduced salivation, hoarseness and hypoplasia of the nipples were common signs. Five patients had frequent respiratory infections.

The mothers lacked more than four permanent teeth, one mother had hypodontia in the deciduous dentition.

The sweat pore counts were low in patients, and lower than normal in the mothers.

All patients carried β‐hemolytic streptococci, four of them group A either in nose or pharynx, without symptoms. Immunoglobulin values, including IgA were normal in serum and saliva.

Unexpectedly, serum parathyreoid hormone concentrations both in patients and mothers were low.

The major problem of the families was the risk of hyperpyrexia due to hypohidrosis, but the patients' concern was mostly because of their facial appearance.
Heritable fragility at 11q13 and 12q13
Authors: Smeets D. F. C. M. , Scheres J. M. J. C. , Hustinx T. W. J.
Published: July 2010

The chromosomes of two mentally retarded probands were investigated because they were suspected of having the fragile X syndrome. However two other fragilities were detected. In one patient a fra(11)(q13) was found and in the other a fra(12)(q13). Family studies revealed that both fragile sites were real heritable ones.

Besides these two heritable fragile sites, the common fragile site at 3p14 was frequently observed. The effects of BUdR, FUdR and methotrexate on the frequency of the three fragilities were studied.

The two heritable fragile sites differed from the common fragile site at 3p14 with respect to their inducibility by FUdR and methotrexate.
A complex structural rearrangement of chromosome 4 in a woman without phenotypic features of Wolf‐Hirschhorn syndrome
Authors: Romain D. R. , Columbano‐Green L. M. , Parfitt R. G. , Chapman C. J. , Smythe R. H. , Gebbie O. B.
Published: July 2010

A 32‐year‐old mentally retarded woman was found to have a complex rearrangement of one chromosome 4. Her karyotype is interpreted as 46, XX, inv(4) (pter→p14::q12→p14::q12→qter) del (4) (pter→15.33::p15.2→qter). Clinically she does not show the features of the Wolf‐Hirschhorn syndrome. Her phenotype and cytogenetic findings are compared with 2 other reported cases of 4p‐ without Wolf‐Hirschhorn syndrome.
I‐cell disease: clinical studies of 21 Japanese cases
Authors: Okada Shintaro , Owada Misao , Sakiyama Takeshi , Yutaka Tohru , Ogawa Minoru
Published: July 2010

Clinical pictures of 21 cases with I‐cell disease patients, 12 males and 9 females, were analyzed. Characteristic coarse facial features and shortness of stature were observed in all cases. In general, the motor development was found to be more severely retarded than the mental development of the patients. Rather little involvement of the nervous system seemed to cause somewhat acceptable mental development in some cases, and also cause the absence of epileptic seizures in all cases. Involvement of the cardiovascular system, especially progressive hypertrophic cardiomyopathy, could be highly responsible for frequent sudden death of I‐cell disease patients.
Steroid sulphatase deficiency disease
Authors: Lykkesfeldt Gert , Høyer Henrik , Ibsen Hans Henning , Brandrup Flemming
Published: July 2010

Seventy‐six ichthyotic male patients with a biochemically confirmed diagnosis of steroid sulphatase deficiency are reported. Ascertainment was based on either a previous diagnosis of placental steroid sulphatase deficiency (21 probands and 15 secondary cases), or ichthyosis with steroid sulphatase deficiency (29 probands and 11 secondary cases). The ichthyotic phenotype of the first group was indistinguishable from that of the other group, and completely fitting the classic description of recessive X‐linked ichthyosis. A prominent skin peeling in early infancy was found to be a characteristic feature of this syndrome. Maldescent of the testis was registered in 9 patients; and testis cancer had been diagnosed in 2 males with normally descended gonads. This high proportion of patients with gonadal abnormalities strongly indicates a relation with the steroid sulphatase deficiency. Corneal opacities, not affecting visual acuity, were seen in 14 out of 28 males by slit‐lamp examination.
Sotos syndrome — autosomal dominant inheritance substantiated
Authors: Winship Ingrid M.
Published: July 2010

Sotos syndrome, or Cerebral Gigantism is recognised as the syndromic association of mental retardation, macrocephaly and prenatal onset of accelerated growth.

A kindred has been investigated in which the father and 4 affected offspring all have the Sotos syndrome. Autosomal dominant inheritance has been postulated in the past, and the family conform to this genetic pattern.
Cortical blindness, growth and psychomotor retardation and postaxial Polydactyly: A probably distinct autosomal recessive syndrome
Authors: Hernández Alejandro , García‐Esquivel Lidia , Reynoso Martha Celina , Fragoso Rubén , Enríquez‐Guerra Miguel Angel , Nazará Zamira , Anzar Miguel Bracamontes , Cantú José María
Published: July 2010

A 14‐month‐old female infant with a syndrome mainly consisting of cortical blindness, psychomotor retardation and postaxial Polydactyly (type B in hands and type A in feet) was studied. Two deceased sibs were similarly affected. Differential diagnosis and the review of medical literature permit the individualization of a distinct syndrome with a probable autosomal recessive pattern of inheritance.
Dandy‐Walker malformation: etiologic heterogeneity and empiric recurrence risks
Authors: Murray Jeffrey C. , Johnson Jennifer A. , Bird Thomas D.
Published: July 2010

The Dandy‐Walker malformation (DWM) includes hydrocephalus, incomplete cerebellar vermis and a posterior fossa cyst. Genetic influences and recurrence risks for DWM have not been well characterized. We report a retrospective study of 21 autopsy‐proven cases of DWM and review the literature regarding an additional 92 subjects. DWM represents marked genetic and etiologic heterogeneity. Recurrence risk for siblings may be high when DWM is associated with a single gene disorder such as the autosomal recessive Warburg and Meckel‐Gruber syndromes. DWM may also result from chromosomal anomalies or environmental factors. When the evidence suggests that DWM has not occurred as part of a Mendelian or chromosomal disorder then the recurrence risk is relatively low (on the order of 1 to 5%). There appears to be an increased frequency of the association of DWM with congenital heart disease, cleft lip/palate and neural tube defects. Based on our study we provide guidelines for the genetic counseling of families having a child with DWM.
Association of parental consanguinity with decreased birth weight and increased rate of early death and congenital malformations
Authors: Magnus P. , Berg K. , Bjerkedal T.
Published: July 2010

Data on parental consanguinity have been recorded for all births in Norway since 1967. Pregnancy outcome for offspring of 848 women mated to their first cousins were compared with offspring of 1,696 control women. The stillbirth rate was 23.6 per thousand for cases and 13.4 for controls. The neonatal death rate was 34.9 per thousand for cases and 14.3 for controls. The recurrence risk for sibs for early death was 9.4% for cases and 4.2% for controls. The mean offspring birth weight was significantly lower (3377 g vs. 3491 g), and the variance in birth weight was slightly larger for cases than controls. The percentage of children with malformations detected shortly after birth was 4.6% for cases and 2.2% for controls. The differences may be attributed to the increased homozygosity in offspring of first cousins. The results have relevance for genetic counselling to consanguineous couples, as well as for the understanding of the etiology of adverse pregnancy outcome and for elucidating the causes of variation in birth weight.
Niemann‐Pick disease type B: first‐trimester prenatal diagnosis on chorionic villi and biochemical study of a foetus at 12 weeks of development
Authors: Vanier Marie T. , Boue Joëlle , Dumez Yves
Published: July 2010

First‐trimester prenatal diagnosis of Niemann‐Pick disease type B was successfully achieved by sphingomyelinase assay on chorionic villi, performed directly and after 3 weeks' culture. Cultured chorionic cells were normally found to exhibit sphingomyelinase activities 3 times higher than seen in the solid biopsy, and showed a lower residual activity in the affected foetus. Their study may thus prove helpful in dubious cases. Enzyme activities and lipid patterns were studied in several organs of the aborted foetus. Lysosomal sphingomyelinase was deficient in all tissues. The lipid pattern of the brain was normal for the age, but a 4‐fold sphingomyelin storage had already taken place in the liver (2.5‐fold in the spleen) of this 12‐gestational week foetus.
Mosaic tetrasomy 12p
Authors: Gilgenkrantz S. , Droulle P. , Schweitzer M. , Foliguet B. , Chadefaux B. , Lombard M. , Chery M. , Prieur M.
Published: July 2010

Mosaic tetrasomy 12p is a dysmorphic syndrome which has been described under the name of Pallister mosaic syndrome and Teschler‐Nicola/Killian syndrome and has sometimes been incorrectly interpreted as tetrasomy 21. Here we report the first case to be diagnosed prenatally and confirmed by enzyme assays, and we summarize the clinical and biological characteristics of all the cases reported so far under various names.
Ectodermal manifestations in Menkes disease
Authors: Moore Charleen M. , Howell R. Rodney
Published: July 2010

Hair and skin pigmentation changes are described in males with Menkes disease from birth to 12 years of age and in 28 obligate carrier or at‐risk females. Pili torti were observed in all affected males and in 43% of the females studied. The presence of pili torti may be considered a reliable diagnostic feature of the carrier state. Suggestions are given for evaluation of the hair in individuals in Menkes pedigrees.
Genetic counseling and genetic heterogeneity in the thalassemias
Authors: Paglietti E. , Galanello R. , Addis M. , Cao A.
Published: July 2010

In this study, we have compared the hemoglobin A2 levels (Hb A2) of α‐thalassemia carriers (‐α/‐α and ‐α/αα genotypes) with those of double heterozygotes for δ+ and β° thalassemia genes, who were identified by family studies and polymorphic restriction site analysis within the β‐globin gene cluster. We found that double heterozygotes for the δ+ and β° thalassemia have significantly (p<0.001) higher Hb A2 levels as compared with carriers of α‐thalassemia. This finding has practical implications in the genetic counseling of subjects with a thalassemia‐like phenotype associated with normal or borderline Hb A2 levels.
Possible teratogenic effects of artificial insemination by donor
Authors: Forse R. A. , Ackman C. F. D. , Fraser F. C.
Published: July 2010

Three trisomic offspring conceived by artificial insemination by donor (AID) were observed in a population in which a total of about 400 babies were so conceived. To test whether this excess represented a random fluctuation or a real effect of the AID procedure we surveyed, by questionnaire, a group of women who had born children conceived by AID. A significantly higher number of trisomic offspring were found than expected in a population with the observed age distribution. Further data are needed to test the validity of this observation.
The characteristic physiognomy and tissue specific karyotype distribution in the Pallister‐Killian syndrome
Authors: Hunter Alasdair G. W. , Clifford Brian , Cox David M.
Published: July 2010

We report a child with clinical features remarkably similar to those of our patient reported as tetrasomy 21 in 1982. Improved banding in this, and the previous case, together with gene dosage studies, and subsequent reports in the literature lead us to conclude that these patients are in fact tetrasomic for 12p. The clinical features of these children are most distinctive and the importance of their recognition lies in the fact that the abnormal cell line is virtually confined to fibroblast studies.
Monosomy 16q: a distinct syndrome Apropos of a de novo del(16) (q2100q2300)
Authors: Rivera Horacio , Vargas‐Moyeda Elvira , Möller Melba , Torres‐Lamas Armando , Cantú José María
Published: July 2010

A 2‐month‐old boy with delayed growth and development, brachycephaly, large anterior fontanelle, low‐set folded ears, micrognathia, aortic coarctation, floppy abdominal muscles, and pes varus, was found to have a 46, XY, del(16)(q2100q2300) de novo karyotype. This observation corroborates both the distinctness of the 16q monosomy syndrome and the pathogenetic role of the band 16q21.
Co‐cultivation studies in the expression of fragile(X) (q27) in lymphocytes
Authors: Webb T. P.
Published: July 2010

Co‐cultivation studies in different combinations have been carried out between cells which have been found to be positive for the fragile(X) (q27) and control cells. As no increase or decrease was discernible in the level of Fra(X) detected in ‘positive’ cells, and no fragility was introduced into the ‘negative’ cells, it was concluded that there had been no intercellular co‐operation, and a diffusible expression or suppression factor was not involved.
Autoimmune polyendocrinopathy – candidosis – ectodermal dystrophy (APECED): autosomal recessive inheritance
Authors: Ahonen Pekka
Published: July 2010

A genetic analysis was made of 58 patients and their 42 families with APECED (autoimmune polyendocrinopathy – candidosis – ectodermal dystrophy). APECED is characterized by hypoparathyroidism, primary adrenocortical failure and chronic mucocutaneous candidosis, but none of its components is constant. Other endocrine deficiencies can occur as well and also dystrophy of dental enamel and nails. The proportion of affected siblings was 0.147 ± 0.034 (S.D.) when corrected for truncate single ascertainment, 0.246 ± 0.019 when corrected for a priori truncate complete ascertainment and 0.240 ± 0.047 when corrected for a posteriori truncate complete ascertainment. The male/female ratio was 1.04. The results are compatible with autosomal recessive transmission. No heterozygous manifestations of the gene were found. The gene is enriched in isolated subpopulations in central and eastern Finland. APECED is part of the “Finnish heritage of disease”.
Maximal low density lipoprotein receptor activity and the effect of lipid lowering diet on total serum cholesterol
Authors: Leren Trond P. , Hjermann Ingvar , Børresen Anne‐Lise , Berg Kåre , Leren Paul
Published: July 2010

This study was undertaken to test if the effect of lipid lowering diet on total serum cholesterol, is influenced by maximal low density lipoprotein (LDL) receptor activity.

LDL receptor activity was determined in cultured skin fibroblasts from hypercholesterolemic, male subjects after lipid lowering diet intervention. The LDL receptor values from 15 subjects (responders) who had responded well to a lipid lowering diet and from 14 subjects (non‐responders) who had responded poorly, were compared. The responders had a reduction in total serum cholesterol of 29.4%, and the non‐responders had a reduction of 8.2% (p < 0.0001). The higher values for LDL receptor activity among the responders did not reach statistical significance. For all 29 subjects there were non‐significant positive correlations between reductions in total serum cholesterol and values for association or degradation of 125I‐LDL at 37°C (r = 0.16, p = 0.40 and r = 0.17, p = 0.38, respectively).

Thus, it seems that maximal LDL receptor activity is not a major predictor for the response of lipid lowering diet on total serum cholesterol levels in hypercholesterolemic subjects without autosomal dominant familial hypercholesterolemia.
Deficiency of fumarylacetoacetase without hereditary tyrosinemia
Authors: Kvittingen E. A. , Børresen A. L. , Stokke O. , Hagen C. B. van der , Lie S. O.
Published: July 2010

A variant of the enzyme fumarylacetoacetase (FAH) (E.C.3.7.1.2) in healthy individuals, determined by the enzyme activity, is reported. Analysis of family members of probands with low FAH activity suggests that the enzyme variant causing low activity could be the product of a pseudodeficiency gene. Assumed homozygotes for this gene have only slightly higher enzyme activity than patients with the metabolic disorder hereditary tyrosinemia I (hepatorenal type). No clinical abnormalities have been found in association with the postulated gene.
Two different clinical and genetic forms of hereditary palmoplantar keratoderma in the northernmost county of Sweden
Authors: NIELSEN POVL GAMBORG
Published: July 2010

A follow‐up study of clinical and genetic observations, made on patients with hereditary palmoplantar keratoderma living in the northernmost county of Sweden (Norrbotten) in 1967, was performed. Two clinical types could be distinguished, a common form with an autosomal dominant mode of inheritance, corresponding to the description of the Unna Thost variety and a severe form with evidently an autosomal recessive inheritance. One of the patients with the severe form had a multilating palmoplantar keratoderma. Neither employment nor dermatophytosis influenced the severity of the hyperkeratosis in any of these two types. Occurrence of hereditary palmoplantar keratoderma together with other genodermatoses or dermatoses with a polygenic mode of inheritance was also found in this study.
C4 allotypes and HLA‐DR antigens in the family of a patient with C4 deficiency
Authors: Sjöholm A.G. , Kjellman N.‐I.M. , Low B.
Published: July 2010

Major histocompatibility complex (MHC) haplotypes, including HLA‐A, ‐B, ‐C and ‐DR and complotypes (BF, C2, C4A and C4B) were determined in a large family with inherited C4 deficiency. The propositus, a 12‐year‐old girl with complete C4 deficiency and SLE, had the MHC haplotypes HLA‐A2,‐Cw3,‐B40,‐DR6, BFS, C2C, C4AQO, C4BQO inherited from her father and HLA‐A30, ‐B8, ‐DR3, BFF1, C2C, C4AQO, C4BQO from her mother. These haplotypes were identified in several of the healthy relatives, who were thus shown to be carriers of C4 deficiency. Most of the other haplotypes found in the family were not considered to be unusual in the general population. The complete absence of C4 in the patient was confirmed by studies of Chido and Rodgers antigens in the plasma and on the erythrocytes, the absence of plasma C4d fragments and by studies of C4 chain antigens by immunoblotting technique. The results of the genetic analysis, together with the findings in other cases of C4 deficiency, supports the possibility that complete C4 deficiency in itself predisposes to development of SLE without contribution of other MHC gene products.
Carrier detection in Duchenne muscular dystrophy using computed tomography
Authors: Stern L. M. , Caudrey D. J. , Clark M. S. , Perrett L. V. , Boldt D. W.
Published: July 2010

In Duchenne dystrophy computed tomography of muscles shows total or partial replacement of normal muscle by low density tissue, presumably representing fat. It was hypothesised that female carriers would have increased fat deposition, and hence lower density readings in certain muscle groups when compared with controls. Three C. T. scans, two through the thigh and one through the calf, were obtained on 9 obligate carriers, 12 “possible” carriers, and 10 controls. A total of 15 density readings in different muscle groups were obtained for each subject. The results, analysing the mean densities in Hounsfield units, show that the obligate carriers have statistically significant lower density readings than controls. The 9 obligate carriers and 10 controls were correctly allocated using discriminant function analysis of muscle density readings. An attempt to assign the “possible” carriers was made. The use of C.T. scanning in addition to creatine kinase (C. K.) estimations will significantly improve accuracy of genetic counselling and has the advantage of being non‐invasive.
Recurrent de novo interstitial deletion of 16q in two mentally retarded sisters
Authors: Hoo J. J. , Lowry R. B. , Lin C. C. , Haslam R. H. A.
Published: July 2010

Two sisters with similar clinical features are described. Their clinical manifestations include mental retardation, delayed speech development, low percentiles for height, weight and head circumference, dysmorphic ears, cubitus valgus, pseudoclubbing of fingers, flexion deformity of toes, small kidneys, elevated serum creatinine and blood urea nitrogen (BUN).

High resolution chromosome analysis revealed a complete deletion of 16qh with a concurrent small deletion of the adjacent euchromatic segment 16q12.1 in one of the no. 16 chromosomes of both sisters, whereas the parents had normal no. 16 chromosomes. Length polymorphism of the 16qh regions appeared to indicate a maternal origin of the deleted no. 16 chromosome in both sisters. The clinical features of both sisters were attributed to the 16q12.1 deletion. Since both parents were cytogenetically normal, the two sisters were considered as a recurrence of a similar de novo interstitial deletion. Possible mechanisms which could lead to recurrence of a seemingly de novo event are discussed.
Genetic screening for artificial insemination by donor (AID)
Authors: Selva J. , Leonard C. , Albert M. , Auger J. , David G.
Published: July 2010

We report the results of our ten‐year experience in the Centre for Study and Conservation of Human Semen (CECOS) in Paris‐Bicetre. A total of 676 potential semen donors were interviewed by a geneticist and karyotyped; 6.0% were excluded, i.e. 2.6% for a cytogenetic reason and 3.4% for a genie reason. Our experience stresses the subjectivity and difficulty of the exclusion decision. It also shows how useful it is to take into account the recipient's familial pathology when choosing the donor. Finally, it reveals the importance of the geneticist's participation in the functioning of a centre.
Fetal mortality in sibships of cases with neural tube defects
Authors: Sadovnick A. D. , Keena B. , Baird P. A. , Hall J. G.
Published: July 2010

Rates of fetal mortality in sibships of probands with neural tube defects (NTDs) may reflect liability to NTDs. Expectations from the multifactorial model predict that fetal loss should be higher in sibships of male probands; in multiplex sibships; and in sibships where the proband had no additional malformations. This was analysed for 715 pregnancies from 398 sibships. In general, the results did not support the expectations of the multifactorial model.
Use of Y chromosome specific probes to detect low level sex chromosome mosaicism
Authors: Tantravahi Umadevi , Bianchi Diana W. , Haley Christine , Destrempes Margaret M. , Ricker Alyne T. , Korf Bruce R. , Latt Samuel A.
Published: July 2010

An individual, found to be a true hermaphrodite at laparotomy, is presented. Cytogenetic studies which initially disclosed a 46,XX karyotype, conflicted with the anatomic presence of a testis. More extensive analysis of peripheral lymphocytes and skin fibroblasts revealed low level 46,XX/69,XXY mosaicism. DNA hybridization studies, using highly repeated Y chromosome specific probes, confirmed the rare presence of Y chromosome bearing cells. Such combined clinical and molecular studies can have an important impact on diagnosis and management of cases in which sex chromosome mosaicism is suspected.
Xp21/autosome translocations
Authors: Holden Jeanette J. A. , Smith Anne , MacLeod Patrick M. , Masotti Ron , Duncan Alessandra M. V.
Published: July 2010

An isolated case of Duchenne muscular dystrophy in a 15‐year‐old retarded girl with a de novo t(X;2) (p21.2;q37) translocation is described. Her clinical history is presented, with particular emphasis on CK level determinations made at several different times during her development. The similarities between this patient and previously reported females with Duchenne muscular dystrophy are discussed with reference to de novo translocations with a breakpoint at Xp21 and the risk of DMD in such females.
Number of “high genes” involved in determining the activity of paraoxonase
Authors: Nielsen Arne , Eiberg Hans , Fenger Kirsten , Mohr Jan
Published: July 2010

The genetics of paraoxonase activity is further analysed on the basis of a Danish family material (Eiberg & Mohr 1981), namely a random sample of the investigated two mating types. The starting point is the earlier assumption that the segregation into high and low activity is due to alleles on a single locus with the frequency 0.726 of low genes (Eiberg & Mohr 1981, Nielsen et al. 1986). It is shown that a hypothesis of two “high genes”, hi and h2 on the same locus, with allele frequencies 0.117 and 0.157, both high genes being dominant over low genes and h2 dominant over hi, may explain the observed pattern of segregation. The hypothesis would imply average activities of genotype 1 hi of 960 μM PNP/1, of lh2 1385 μM PNP/1, of h1h2 1202 μM PNP/1, and of h1, h2 and h2h2 2048 μM. PNP/1. It cannot be excluded that there are more than two “high genes”. It is further shown that more than one “low gene” must be involved.
Structure, origin and effects of a supernumerary marker chromosome 15
Authors: Schmid M. , Schindler D. , HAAF T.
Published: July 2010

A de novo supernumerary small marker chromosome 15 was observed in a female infant with mental and statomotoric retardation as well as minor facial dysmorphia. The marker chromosome was analysed by ten different staining techniques and 5‐azacytidine treatment of lymphocyte cultures. It is shown that the supernumerary chromosome was derived by a non‐sister chromatid exchange between the two homologous maternal chromosomes 15. The cytogenetical properties of the marker chromosome, the different activity of its two nucleolus organizer regions and the somatic pairing configurations revealed by 5‐azacyidine are reported.
Partial deletion of the short arm of chromosome 3: further delineation of the 3p25 ‐ 3pter syndrome
Authors: Reifen R. M. , Gale R. , Kerem E. , Armon Y. , Brand A. , Dagan J. , Kohn G.
Published: July 2010

A male newborn with partial deletion of the short arm of chromosome 3 is described. The patient shares most of the features with the previously reported cases. In addition, cardiac, skeletal and gastrointestinal anomalies not previously reported are described. These characteristics may help in further delineation of the syndrome.
Cerebroside‐β‐glucosidase activity in Gaucher brain
Authors: Svennerholm Lars , Månsson Jan‐Eric , Rosengren Birgitta
Published: July 2010

Cerebroside‐β glucosidase (acid β ‐glucosidase) activity was determined in the forebrain from three patients with the infantile type of Gaucher disease, six patients with the Norrbottnian type and one patient with a mixed infantile/Norrbottnian type. The forebrain from ten subjects, aged 3 months to 20 years, served as controls. The activity was assayed with the natural substrate, (glucose‐β3H) nervonoylglucosylsphingosine and the artificial fluorogenic 4‐methyl‐umbelliferyl‐β ‐glucoside. The average residual activities of β ‐glucosidase were 12% in the Norrbottnian type and 5% in the infantile type when determined with natural or artificial substrate. Optimum discrimination of the two types of Gaucher disease was obtained with the natural substrate.
Unusual pedigree patterns in seven families with spinal muscular atrophy; further evidence for the allelic model hypothesis
Authors: Bouwsma G. , Leschot N. J.
Published: July 2010

Clinical and genetic findings are presented in 18 patients, from 7 pedigrees with different types of spinal muscular atrophy (SMA). The SMA diagnosis was based on EMG and muscle biopsy findings. All 7 pedigrees show an unusual genetic pattern, not consistent with simple autosomal recessive inheritance. Furthermore, in 6 of the 7 pedigrees different types of SMA were present within each pedigree. Our findings can be explained by an extension of a multiple alleles hypothesis originally described by Becker in 1964.
Growth curves for height in Noonan syndrome
Authors: Witt David R. , Keena Beth A. , Hall Judith G. , Allanson Judith E.
Published: July 2010

Growth retardation is a relatively consistent feature of Noonan syndrome but a standardized growth curve for height has never been calculated. Analysis of retrospective growth data on 112 patients with Noonan syndrome has permitted the establishment of preliminary reference growth standards for height for males and females. The results confirm the clinical impression that short stature among this group of patients occurs uniformly and is independent of chronological age. Various factors which may modify this are considered.
Genetic modelling in schizophrenia according to HLA typing
Authors: Smeraldi E. , Macciardi F. , Gasperini M. , Orsini A. , Bellodi L. , Fabio G. , Morabito A.
Published: July 2010

Studying families of schizophrenic patients, we observed that the risk of developing the overt form of the illness could be enhanced by some factors. Among these various factors we focused our attention on a biological variable, namely the presence or the absence of particular HLA antigens: partitioning our schizophrenic patients according to their HLA structure (i.e. those with HLA‐A1 or CRAG‐A1 antigens and those with HLA‐non‐CRAG‐Al antigens, respectively), revealed different illness distribution in the two groups. From a genetic point of view, this finding suggests the presence of heterogeneity in the hypothetical liability system related to schizophrenia and we evaluated the heterogeneity hypothesis by applying alternative genetic models to our data, trying to detect more biologically homogeneous subgroups of the disease.
Discoid lupus erythematosus‐like skin lesions in a patient with autosomal recessive chronic granulomatous disease
Authors: Strate M. , Brandrup F. , Wang P.
Published: July 2010

A case of chronic granulomatous disease (CGD) in a 32‐year‐old female with two episodes of opportunistic infections is described. At the age of 29 the patient was suspected to be a carrier of X‐linked CGD on the basis of discoid lupus erythematosus‐like skin lesions. No respiratory burst activity, as measured by phorbol myristate acetate stimulated superoxide production, was observed in isolated neutrophils of the patient. Membrane‐rich fractions elicited no superoxide production in the presence of NADPH. The neutrophil content of cytochrome b_245 was within normal range. Family investigations revealed neither cellular abnormalities nor any history of skin diseases or opportunistic infections in first degree relatives. The parents of the patient were first cousins. On the basis of family history and the in‐vitro assessment of neutrophil function, the patient is believed to have autosomal recessive CGD. The presented case illustrates that lupus erythematosus‐like skin lesions are not restricted to female carriers of X‐linked CGD, but may also be found in the autosomal recessive type of the disease.
Skeletal maturation in the XY female syndrome
Authors: GELDEREN H. H. VAN
Published: July 2010

The assessment of bone age in eleven prepuberal patients with XY‐female syndrome shows that skeletal maturation in these patients follow a male pattern. This supports the concept of a factor on the Y chromosome regulating skeletal maturation in the first ten years of life. Tall stature does not seem to be a feature of this syndrome in childhood.
The fetal pathology of the XXXXY‐syndrome
Authors: Rehder Helga , Fraccaro M. , Cuoco Cristina , Gimelli G. , Porro E.
Published: July 2010

A second case of fetal XXXXY‐syndrome detected by prenatal chromosome analysis is presented. The pathological findings include a facial aspect featuring fetal Down's syndrome, hypogenitalism and hypogonadism with excessive reduction of germ cells and also skeletal abnormalities that may be interpreted as early changes, preceding phalangeal shortening V and radioulnar synostosis.
Chromosomal mosaicism and maternal cell contamination in chorionic villi cultures
Authors: Schulze Bernt , Miller Konstantin
Published: July 2010

In a series of 110 chromosome analyses, after chorionic villus sampling, mosaics were found in 3 out of 106 long term cultures. In all 3 cases, subsequent amniotic fluid cell cultures showed normal karyotypes. Maternal cell contamination was encountered in one long term culture derived from carefully dissected chorionic villi.
Distal 11q monosomy. The typical 11q monosomy syndrome is due to deletion of subband 11q24.1
Authors: Fryns J. P. , Kleczkowska A. , Buttiens M. , Marien P. , Berghe H. VAN DEN
Published: July 2010

In this paper we describe two new patients with distal 11q monosomy and precisely localize breakpoints using high resolution banding techniques. The findings in these two patients further contribute to the precise localization of the crucial band for 11q monosomy syndrome as being at 11 q24.1. A very distal 11 q24.2 deletion in the second patient resulted in a completely different phenotype.
Klinefelter's syndrome in Sardinia
Authors: Filippi G.
Published: July 2010

265 hypogonadic Sardinian males, ascertained through military records of 600,000 conscripts approximately over the last thirty‐seven years, were screened for their sex chromatin phenotype by buccal mucosa smears and for their karyotypes from peripheral blood lymphocyte cultures. 158 (59.4%) showed a XXY karyotype without mosaicismo, 5 XX and 1 XXYY karyotypes. Seven sex chromatin negative males had Kallmann's syndrome. This report summarizes the genetic and clinical data recorded in this population sample as opposed to those reported from fertility clinics.