bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult‐onset hereditary cerebellar ataxia and neurosensory deafness
Authors: Schimke R. Neil
Published: July 2010

A family has been studied in which four sibs were affected with an adult‐onset form of cerebellar ataxia and deafness. The ataxia and hearing loss have been slowly progressive over a 10 year follow‐up period, and no other neurological signs have developed in the interim. This variety of hereditary ataxia, which appears to be a distinct autosomal recessive entity, is compared and contrasted with other genetic types, compiled in tabular form. It is emphasized that closer attention to other symptoms, either in the central nervous system or elsewhere, might have considerable use in the differential diagnosis of these conditions and thus provide for more effective genetic counselling.
Familial D/D translocation t(13q;14q) Eight members in four generations
Authors: Centerwall Willard R. , Merrell Preston R.
Published: July 2010

Eight family members spanning four generations were found to have 45 chromosome count D/D translocation identified by Giemsa‐trypsin banding as t(13q;14q). The only mature male is believed to be infertile on the basis of a very low sperm count with reduced motility. This is believed to be related to the chromosome aberration and not to be coincidental. Aside from this, all were clinically normal except the index case, a young girl with unusual facies and moderate to severe retardation of growth and development. It is believed that her abnormalities were coincidental to the chromosome translocation and fortuitous in locating this family and initiating the pedigree. This example of essentially benign (some males are fertile) Robertsonian centric fusion in humans lends itself to interesting speculations about the results from chance matings between such translocation carriers.
Genetics of acheiropodia (“the handless and footless families of Brazil”)
Authors: Freire‐Maia Ademar
Published: July 2010

The acheiropodia data are shown to be consistent with the hypothesis of a fully penetrant gene in the homozygous state. The expressivity is shown to be generally constant, with some minor variation between individuals as well as between the two sides of the same affected person.
A familial F/G translocation [t(20p‐; 22q+)] observed in three generations
Authors: Cohen Maimon M. , Davidson Ronald G. , Brown Judith A.
Published: July 2010

A family is described in which a translocation between chromosomes 20 and 22 has been observed in three generations. Two first cousins with remarkably similar malformations and mental retardation have identical karyotypes which, after chromosome banding, were interpreted as partially trisomic for the short arm of chromosome No. 20.
Cystic fibrosis heterozygote detection: A study on a normal population
Authors: Danes B. Shannon
Published: July 2010

Detection of the cystic fibrosis (CF) heterozygote by testing for cystic fibrosis factor activity (CFFA) in serum samples using bioassays has been reported to give unreliable results. The present study was undertaken to find whether the use of medium from short term white blood cell or skin fibroblast cultures, rather than serum, as the test sample would eliminate such inconsistencies. Short term white blood cell cultures were established from 107 normal, healthy individuals. Cultures from 97 had no CFFA, six (No. 1–6) showed variable results and four (No. 7–10) had activity in all four tests done on a single sample. When the assays were repeated 3 months later on new cultures from these four positive CFFA individuals, two showed activity (Nos. 7 & 9) and two did not (Nos. 8 & 10). All 10 individuals whose cultures showed CFFA had histories of allergies. The association of CFFA in the culture medium derived from individuals having allergies with the intermittent presence of this activity suggested that environmental factors induced a CFF‐like activity in such white blood cell cultures. The oyster ciliary assay, using medium from white blood cell cultures, cannot be used for screening for the CF heterozygote since the substitution of culture medium for serum did not eliminate inconsistent results and CFFA was not specific by this assay for the CF gene.

Of the fibroblast lines established from the four persons whose initial white blood cell cultures consistently showed CFFA, only one (No. 7) showed the CF culture phenotype (CFFA positive and metachromasia).
A new case of the trisomy 9p syndrome: Report of a patient with unusual chromosome findings (46,XX/47,XX, + i (9p)) and a peculiar congenital heart defect
Authors: Orye E. , Verhaaren H. , Egmond H. Van , Devloo‐Blancquaert A.
Published: July 2010

A girl is described for whom an unusual chromosome constitution was found and who had a peculiar congenital heart defect. The girl showed the main clinical features of the trisomy 9p syndrome, such as psychomotor retardation, microcephaly and brachycephaly, enophthalmos, antimongoloid eye slant, hypertelorism, abnormal ears, a globulous nose, downward slanting mouth, hypoplasia of phalanges and abnormal palmar creases. In addition, the girl had an incomplete harelip, a cleft palate and a peculiar congenital heart defect, a ventricular septal defect with pulmonary valve stenosis and a marked hypoplasia of the pulmonary trunk, including the bifurcation. Chromosome analysis revealed a mosaicism with normal and abnormal mitoses (47 chromosomes). The extra chromosome was a metacentric E16–like chromosome, which on the basis of the G, R, Q and Giemsa‐11–banding could be identified as an isochromosome of the short arm of chromosome 9 (46,XX/47,XX,+ i (9) (pter?cen?pter)). The patient consequently had a partial tetrasomy of the short arm of chromosome 9.
Familial primary vesicoureteral reflux
Authors: Fried K. , Yuval E. , Eidelman A. , Beer S.
Published: July 2010

Two families with all children affected by primary vesicoureteral reflux are reported. Both sets of parents were examined and onIy in one family the mother was also affected by unilateral reflux. This congenital lesion has only recently been recognized as a common disease, but because diagnosis depends on voiding cystography, it is not made until the child or adult becomes symptomatic or presents with end‐stage renal disease. As most cases are sporadic, a multiple factorial mode of inheritance is most probable, but an autosomal dominant or recessive gene cannot be excluded as the cause of the disease in some families. It is recommended that all first degree relatives of the patients should be investigated, in order to detect asymptomatic cases of this condition, which is likely to cause progressive renal damage and may have fatal termination due to renal failure.
An XX male: Cytogenetic and endocrine studies
Authors: Rios Maria E. , Kaufman Robert L. , Sekhon Gurbax S. , Bucy James G. , Bauman Joan E. , Jacobs Lawrence S.
Published: July 2010

A 3 year old black male with ambiguous genitalia had a 46, XY karyotype in a bone marrow culture and an intermediate buccal smear result, suggestive of a mosaic of chromatin positive and chromatin negative cells. Upon re‐evaluation at age 15 years, he had a 30% positive buccal smear and a 46, XX karyotype in cultures of peripheral blood lymphocytes, skin fibroblasts, bone marrow, and testis. No Y‐body fluorescence was detectable in interphase cells from the testicular biopsy or the various cultures.

The testicular biopsy appeared similar to that of XXY males, and primary hypogonadism was documented by elevated LH (107 mIU/ml) and FSH (57 mIU/ml) levels in conjunction with low testosterone (142 ng/100 ml). Administration of hCG produced qualitatively normal acute responses of testosterone and estrogens.

The cytogenetic data provide support for the theory that at least some XX males once had a Y‐containing cell line which was subsequently lost.
Amniotic fluid alphafetoprotein measurements in the early prenatal diagnosis of central nervous system disorders
Authors: Brock D. J. H. , Scrimgeour I. B. , Nelson M. M.
Published: July 2010

Amniotic fluid alphafetoprotein (AFP) has been measured in 520 pregnancies between 8 and 24 weeks of gestation. The normal range of values has been defined for fortnightly periods between these limits. Grossly elevated AFP concentrations were found in four pregnancies leading to spina bifida and nine pregnancies leading to anencephaly. Slightly elevated AFP concentrations were found in one twin pregnancy and two pregnancies affected by rhesus isoimmunisation. Normal AFP values were observed in 36 amniotic fluids from pregnancies where the outcome was rhesus isoimmunisation, an inborn error of metabolism, a cytogenetic disorder or a birth defect unrelated to the central nervous system. The reliability of amniotic fluid AFP in the early prenatal diagnosis of spina bifida and anencephaly and the possibility of performing assays on samples sent by post from any part of the world are emphasized.
Alpha fetoprotein levels in maternal serum and in amniotic fluid from early normal pregnancies
Authors: Nørgaard‐Pedersen B. , Lindsten J. , Philip J.
Published: July 2010

Alpha fetoprotein (AFP) was determined in serum from 241 women in the 8th to 43rd week of gestation by quantitative radioimmunoelectrophoresis, and in 103 amniotic fluid samples from the first half of pregnancy by rocket immunoelectrophoresis. Both serum and amniotic fluid samples were obtained from a larger material, but samples were included only from pregnant women whose infants were normal at birth. The 90% normal AFP range was calculated both for maternal serum and for amniotic fluid.
X‐linked hypoxanthine‐guanine phosphoribosyltransferase deficiency without neurological disorders. A report of a family
Authors: Toyo‐Oka Teruhiko , Hanaoka Fumo , Akaoka Ieo , Yamada Masa‐Atsu
Published: July 2010

A patient is reported with X‐linked hypoxanthine‐guanine phosphoribosyltransferase (HGPRT) deficiency. He had gout but no neurological symptoms. The patient had negligible HGPRT activity as determined by thin layer chromatography and liquid scintillation counting. Autoradiography of fibroblast cultures revealed no uptake of 3H‐hypoxanthine. His mother and two sisters were shown to be heterozygotes.
Familial amyotrophic lateral sclerosis with dementia: A second Canadian family
Authors: Pinsky Leonard , Finlayson M. H. , Libman I. , Scott B. H.
Published: July 2010

A family with adult‐onset amyotrophic lateral sclerosis (ALS) and dementia is described. The father presented with lower motor neurone disease affecting the legs. A son presented with bulbar paralysis. Neither developed dementia. A daughter presented with spastic right lower limb weakness. Two years later, she developed a rapidly progressive mental disorder. Her cortical pathology had a distinctive fronto‐temporal distribution. The rarity of published reports on ALS with dementia in families outside the Western Pacific and the factor of parental consangcinity conspired to make genetic counselling for this family difficult.
Mental retardation and congenital malformations associated with a ring chromosome 6
Authors: Fried K. , Rosenblatt M. , Mundel G. , Krikler R.
Published: July 2010

A boy, in whom a ring chromosome 6 was found, presented with mental retardation and odd facies. He had a small head, bilateral epicanthus, broad nasal bridge, low set prominent ears, short neck and clasped thumbs. The ring chromosome was identified by the ASG banding technique.
Evidence for recessive inheritance of myopia
Authors: Karlsson Jon L.
Published: July 2010

Data are presented on the family distribution of nearsightedness, including the frequency of the disorder in the children of two myopes. The previous literature is reviewed, embracing several quantitative family or population studies in addithn to extensive pedigree material. It is concluded that there is substantial evidence that recessive inheritance is the principal mechanism of transmission, and that most instances of myopia probably fall into that category.
Ring chromosome 13 syndrome
Authors: Fried K. , Rosenblatt M. , Mundel G. , Krikler R.
Published: July 2010

A girl in whom a ring chromosome 13 was found, presented with microcephaly, mental retardation and multiple minor malformations. She was born after a full term pregnancy, small for date and with a small head circumference. She underwent craniotomy at the age of 18 months because of premature closure of the metopic sutures. At age 41/2 years, she presented with mental retardation, microcephaly, asymmetrical mongoloid slanting of narrow palpebral fissures, bilateral epicanthic folds, broad and prominent nasal bridge, normal sized ears and open mouth. She had somewhat short second and fifth fingers, with a single crease on the right fifth finger and normal thumbs. This case supports previous reports that a clinically recognizable ring chromosome 13 syndrome can be defined.
The significance of “unspecific neuropathy” in hereditary ataxias and related disorders
Authors: Skre Håvard
Published: July 2010

Neurological findings such as polyneuropathy, hyporeflexia, deformities, ataxic signs, and inverted plantar responses were found more frequently in unaffected sibs and other close relatives of people with hereditary ataxias or allied disorders (HA) than in a normal population sample. Introduction of a scoring system for neurological signs allowed the degree of neurological impairment to be estimated. The number of people with scores exceeding the limit of normality (sum score higher than 3.4) was counted among the members of HA families. This number was found to be greater in families where HA segregated as a recessive trait than in those where it segregated as an autosomal dominant trait.

The frequency of cases with high scores (“unspecific neuropathy” (Un)) observed in 1st and 2nd degree relatives of patients with dominant HA, suggested a hereditary basis for Un. The ratios were not compatible with simple Mendelism, but the observations fitted well with a hypothesis of polygenic inheritance. Un clustering in families with autosomal dominant HA could be due to a selection phenomenon through a negative assortative mating.

Un cases observed in families with recessive HA may, in several instances, reflect disease manifestations in heterozygotes.
A computer‐oriented linkage analysis scheme
Authors: Freidhoff Linda B. , Chase Gary
Published: July 2010

A comprehensive, computer‐oriented scheme for genetic linkage analysis is described. It computes the likelihood of a complex pedigree allowing for many non‐standard features including multiple alleles (up to four per locus), multiple mates, more than one mating in the eldest generation, consanguinity, missing or partially tested persons, and different recombination fractions between males and females.

The program works by computing weighted likelihoods in a vertical, descending fashion. First, the set of possible genotypes for the members of the eldest generation is determined and prior probabilities assigned to these states of nature (based on gene frequency calculations). Phenotypic information is used to modify these probabilities in the standard manner. Then, for a particular set of genotypes, the conditional likelihood of the remainder of the pedigree is computed. This calculation may itself be many‐branched and therefore a computer is necessary to keep track of the stages of the process. When the youngest generation has been taken into account, a final likelihood is determined, reflecting all information in the pedigree.

The current version of the program successfully calculates the exact likelihood of a complex pedigree which was designed to exploit the non‐standard features of the program. It has also computed likelihoods for a published pedigree, and the results are essentially equal to those obtained by the other authors using a previously available computer scheme for linkage analysis.
Polycythemia Vera treated with 32P and Myleran: Development of chronic granulocytic leukemia with chromosomal abnormalities in one patient
Authors: Stavem Per , Hagen Carl B. van der , Vogt Else , Sandnes Kjell
Published: July 2010

Chronic granulocytic leukemia developed in a 59–year‐old woman who had previously received a total of 21 mCi 32P for polycythemia Vera. She was treated with Myleran (busulphan) for her chronic granulocytic leukemia. Cytogenetic studies revealed deletion of chromosomes No. 8 and 12, and translocation between 1 and 8. The patient also developed a severe autoimmune hemolytic anemia, for which she received prednisone treatment. She died with a perforated stomach ulcer.
A case of trisomy 8 mosaicism 47, XX, + 8/46, XX
Authors: Aller V. , Abrisqueta J. A. , Perez A. , Martin M. A. , Goday C. , Mazo J. Del
Published: July 2010

The cytogenetic study is reported of a female infant affected with several malformations and presenting a mosaicism of the type 47,XX, + 8/46,XX in her karyotype. G‐band analysis and the distribution curves of these bands were studied in order to obtain a more objective identification of trisomy 8. Results of Q‐banding, X‐chromatin and der‐matoglyphic studies are given and compared with previous reports.
Familial occurrence of the G syndrome
Authors: Biervliet J. P. G. M. Van , Hemel J. O. van
Published: July 2010

We report the familial occurrence of the G syndrome of multiple congenital anomalies affecting a mother and her three sons. All showed the characteristic syndromal facies, a low total ridge count, pronounced hypertelorism, mild mental retardation, and severe dysphagia in infancy which improved with age but persisted in the boys (it has disappeared in the mother). One of the boys had a left cleft lip and cleft palate, another had a unilateral cleft lip. All boys had hypospadias: penile in two (with descended testes) and perineal in another (with cryptorchidism). Familial occurrence in this family is compatible with autosomal dominant inheritance.
Genetics of the GPT system. Family, mother/child and association studies
Authors: Olaisen Blørner
Published: July 2010

GPT types are presented for 150 Norwegian matings, with 454 children, and 1703 Norwegian mother/child combinations. There were five exceptions to a simple codominant inheritance pattern, all believed to be due to a segregating Gpl0‐allele. Rare phenotypes were encountered in two of the families and in 11 of the motherlchild combinations. Compiled family material and mother/child material are presented.

No indication of association was found between GPT types and phenotypes within the ABO, Rh, MN, Hp, Gc, C3, PGM1, and ACP1 systems. There is a marked association between EBS‐Ogna (epidermolysis bullosa simplex, type Ogna) affection and GPT phenotypes. This reflects the Gpt‐EBS1 linkage phase. No evidence was found of association between GPT phenotypes and either nephrological diseases or PKU (phenylketonuria).
Asymmetric septal hypertrophy in a large Amish kindred
Authors: Glenn  , Bingle J. , Dillon James , Hurwitz Roger
Published: July 2010

We report a large Amish kindred in which asymmetric septal hypertrophy (ASH) appeared to segregate as an autosomal dominant gene. This kindred was ascertained through a 3–month‐old infant and her father. The striking differences between father and daughter regarding clinical presentation and course exemplify the variable expressivity of this condition. The importance of genetic factors in diagnosis and counseling are discussed. Previous reports of ASH in infants and children are reviewed.
Physical and mental defect of chromosomal origin in four individuals of the same family. Trisomy for the short arm of 9
Authors: Blank C. E. , Colver Doreen C. B. , Potter A. M. , McHugh J. , Lorber J.
Published: July 2010

A family with the reciprocal translocation t(9;22)(q13;qll) segregating in genetically balanced and unbalanced form is identified. The clinical features of four members with trisomy for the short arm of 9, and the proximal part of the long arm of 9, are described in detail. Features in common are summarized and compared with developmental abnormality observed in other examples of trisomy for the short arm of 9. An attempt is made to delineate further the clinical features commonly seen in trisomy for the short arm of 9.
Dominant mesomelic dwarfism of the hypoplastic tibia, radius type
Authors: Leroy J. G. , Vos J. De , Timmermans J.
Published: July 2010

A new type of mesomelic dwarfism in two male siblings and their father is presented. The responsible mutant gene manifests itself phenotypically as a severe dysostosis of the tibia with shortening, bowing and pseud arthrosis and as a mild dysostosis of the radius. The fibulae and ulnae are secondarily affected, but the rest of the skeleton is normal. The disorder has an autosomal dominant mode of inheritance. It can be differentiated rather easily from the already known forms of mesomelic dwarfism.
Friedreich's ataxia in Western Norway
Authors: Skre Håvard
Published: July 2010

Friedreich's ataxia (FA) was investigated in Western Norway, an area comprising several isolated communities and with a population of 725,000 as at 1 January 1968. The prevalence of FA was estimated to be 1/100,000 in this population. An autosomal recessive mode of transmission appeared likely in all instances.

The gene frequency was only 7.9.10‐‐5, but the consanguinity rate was high in the families observed. The mutation rate was relatively high at 1.6.10‐‐5.

The clinical features displayed by the 10 examined patients agreed well with those observed by other investigators. Spinal and cerebellar ataxia dominated the clinical picture. In most cases signs of peripheral neuropathy were also observed. Epilepsy was seen in some cases, and also dementia.

Unspecific neuropathy, defined according to a scoring system may represent disease manifestation in FA heterozygotes.
Familial balanced (7;11;21)translocation and Down's syndrome in two siblings
Authors: Schwinger E. , Mikkelen Margareta , Niesen Mathilda
Published: July 2010

Cytogenetic studies of a family with two children with Down's syndrome have revealed a balanced reciprocal translocation between chromosomes No. 7, 11 and 21 in the mother. One of three daughters has inherited this translocation; two mongoloid daughters have a supernumerary chromosome No. 21 in addition to the translocation.
Materno‐fetal ABO incompatibility as a cause of spontaneous abortion
Authors: Lauritsen J. Glenn , Grunnet N. , Jensen O. Myhre
Published: July 2010

In a series of 288 spontaneous abortions occurring during the first 16 weeks of gestation, simultaneous karyotyping and ABO blood grouping of 555 of the parents were carried out. In 74 of the 288 chromosome‐analyzed abortuses, the ABO blood group of the fetus was determined by the immuno‐fluorescence technique and the mixed cell agglutinating reaction in fetal tissue. The results of the blood grouping were compared with the ABO blood group frequencies of 8818 blood donors from the same area.

Among abortuses with normal karyotype, a significantly higher frequency of ABO incompatibility was found between mother and fetus (P < 0.005) and also between mother and father (P < 0.01) in comparison with abortuses with abnormal karyotype. Furthermore, the ABO blood group frequencies of the karyotypically normal fetuses deviated significantly from those of fetuses with abnormal karyotypes (P < 0.001). No significant difference was found when the total ABO frequencies of the abortuses and of their parents were compared with the frequencies in the control group.

It is concluded that the ABO incompatibility between mother and fetus is likely to be a cause of early spontaneous abortions, but almost exclusively in chromosomally normal abortuses. In the present series of cases, the maximum fraction of abortions caused by materno‐fetal ABO incompatibility is estimated to be 18 %.
Trisomy 9p in a patient with a de novo 9/15 translocation
Authors: Jacobsen Petrea , Hobolth Niels , Mikkelsen Margareta
Published: July 2010

Mental retardation, facial dysmorphism, hypertelorism, antimongoloid eye slants, epicanthus, globular nose, malformed ears, bone abnormalities, one flexion crease on 5th finger, simian crease, and speech difficulties with delayed expressivity were found in a girl with trisomy of the short arm of chromosome 9. The 9p+ syndrome was due to a sporadic translocation of the short arm of chromosome 9 onto the short arm of chromosome 15.
Focal dermal hypoplasia syndrome in a male
Authors: Toro‐Sola Maria A. , Kistenmacher Mildred L. , Punnett Hope H. , DiGeorge Angelo M.
Published: July 2010

Focal dermal hypoplasia (Goltz syndrome) is characterized by a pathognomonic abnormality of the skin in association with other congenital defects. There are only seven males among the 52 reported cases. We report the eighth case in a male and evaluate the possible genetic origin of the syndrome. A critical review of the literature provides no evidence for the previously accepted single gene mode of inheritance.
Two cases of 8p trisomy in one sibship
Authors: Chiyo Hide‐Aki , Nakagome Yasuo , Matsui Ichiro , Kuroki Yoshikazu , Kobayash Hideo , Ono Kazuo
Published: July 2010

Two cases of 8p trisomy in one sibship are presented. The father was a balanced carrier of a translocation rep (8;13) (p11; q34). Case 1 was a 2‐year‐old boy with multiple minor anomalies and severe mental retardation. Giemsa banding studies revealed that he was trisomic for the greater part of 8p (8p11 → pter). When his mother became pregnant again, amniocentesis was carried out in the 17th week of gestation. The fetus (Case 2) was shown to have the same 8p trisomy as Case 1. The pregnancy was terminated in the 22nd week. An autopsy revealed no major anomalies. Clinical features of cases with 8 and 8p trisomy are reviewed briefly.
Lp(a) lipoprotein/pre‐ß1‐lipoprotein in Swedish middle‐aged males and in patients with coronary heart disease
Authors: Dahlén G. , Berg K. , Gillnäs T. , Ericson C.
Published: July 2010

A strong, positive association (P < 0.0001) was found between the presence in serum of pre‐β1‐lipoprotein upon electrophoresis in 0.5% agarose and the Lp(a+) phenotype in a series of 103 males aged 50–52 years participating in a health control study and in a series of 58 patients with sustained myocardial infarction. Both lipoprotein phenomena were more prevalent in the 58 patients than in the 103 presumably healthy males.

The lack of any significant difference between total cholesterol values in the patients and the controls, despite the higher frequency of phenotype Lp(a+) in the former group, argues against the suggestion by Walton et al. (1974) that the increased Lp(a+) frequency in patients with coronary artery disease may be caused by a general increase in the concentration of low density lipoproteins (LDL).
Linkage investigation of a large family with Reifenstein's syndrome
Authors: Ott Jurg , Goldstein Joseph L. , Harrod Mary I.
Published: July 2010

Linkage analysis of a 116‐member family with 11 males affected by Reifenstein's syndrome is reported. One X‐chromosomal and eight autosomal markers were used. Close linkage can be excluded for P, K, MNS and Xga. A possibility of close linkage to ABO is discussed.
Investigations on Huntington's disease in the Canadian Prairies
Authors: Shokeir M. H. K.
Published: July 2010

One hundred and sixty‐two confirmed cases of Huntington's disease have been ascertained in the provinces of Saskatchewan and Manitoba in the Canadian Prairies. They were encountered in 97 sibships which were derived from 58 kindreds. The prevalence of the disorder was estimated to be 8.4 per 100,000 individuals. Taking into account the mean age of onset of the disorder, 23.3 per 100,000 individuals are expected to be heterozygous for the Huntington's disease allele, the frequency of which is thus computed to be 0.0001168.
Investigation on Huntington's disease in the Canadian Prairies
Authors: Shokeir M. H. K.
Published: July 2010

The reproductive performance of 157 patients with Huntington's disease, their 170 normal siblings and 150 matched unrelated controls is presented. Comparison with the general Canadian Prairie population in the appropriate age group is undertaken. Patients with Huntington's disease are not only more fecund than their unaffected sibs but also out‐reproduce unrelated normal controls and members of the general population of corresponding age. Their fitness is thus estimated to be 1.14. Should the present reproductive pattern continue, the allele for Huntington's disease will double its frequency with consequent doubling of the prevalence of the disorder in six generations or approximately 150 years' time.
A simple combinatorial method for calculating genetic risks
Authors: Maag U. R. , Gold R. J. M.
Published: July 2010

A method is presented whereby genetic counsellors can calculate genetic risks in a wide variety of circumstances using only arithmetics. The method is general in that it can handle such information as gene frequency, mutation rate, mode of inheritance, penetrance, pedigree to which the consultand belongs, phenotype of the consultand and his relatives, biochemical findings, etc. Each of the possible combinations of genotypes which may be present in the pedigree is listed and considered in turn. The method consists of a series of simple steps leading mechanically to the right answer.
Familial Kallmann syndrome with unilateral renal aplasia
Authors: Wegenke J. D. , Uehling D. T. , Wear J. B. , Gordon E. S. , Bargman J. G. , Deacon J. S. R. , Herrma J. P. R. , Opitz J. M.
Published: July 2010

On the basis of studies in two brothers and their double first cousin, the Kallman syndrome (KS) is discussed as an X‐linked syndrome of anosmic hypogonadotropic hypo‐gonadism. The anosmia is thought to represent agenesis or hypoplasia of the olfactory lobes, the mildest form of the alobar holoprosencephaly developmental field defect; this is supported by the finding of hypotelorism in two of the patients and their mother. The endocrine defect is thought to represent a hypothalamic abnormality of the luteinizing hormone releasing hormone; borderline normal intelligence may represent another pleio‐tropic CNS manifestation of the KS gene. All three affected males had unilateral renal aplasia, associated in one with ipsilateral abyence of the testis. The presence of at least two developmental field defects (involving the CNS and urogenital system) makes it likely that the KS is a true multiple congenital anomaly syndrome; this is supported by the finding of additional, mostly minor, anomalies reported by other investigators. Heterozygous females may also show manifestations of anosmia, hypogonadism, possibly even internal genital malformation; however, genetic heterogeneity of anosmic hypogonadism is pos?ible, and for the time being it is probably better to designate sporadic female cases of anosmic hypogonadism as examples of the olfacto‐genital syndrome of DeMorsier. Linkage studies are urgently needed to clear up the question of genetic heterogeneity and to help develop empiric recurrence risk figures in anosmic hypogonadism.
Neonatal neurofibromatosis: unusual manifestations with malignant clinical course
Authors: Apter Naomi , Chemke Juan , Hurwitz Nina , Levin Stanley
Published: July 2010

A family with neurofibromatosis is reported in which the proband was an infant in whom the diagnosis was established at birth. In this case, the presenting symptom was a large tumor of the tongue and macrocephaly. Cafe‐aula it spots appeared early, as did additional subcutaneous tumors, with skeletal involvement and severe psychomotor retardation. The rapid growth of the tumor, its spread within the mediastinum, neck and oral cavity, led to a strangulating death at one year of age. The disease originates from early embryonic involvement of the neural crest and from tissues derived from its caudal end. It is probably caused by a single pleiotropic gene transmitted as an autosomal dominant trait, with varying expression of the disease in different members of the same family.
XX males: two new cases
Authors: Yunis Emilio , Cruz Emilia de De La , Nossa Marco A. , Gutierrez Guillermo
Published: July 2010

Two new cases of phenotypic males with 46, XX karyotype are presented. Fluorescence, autoradiographic and centromeric heterochromatin studies in several lines, including testi‐cular cells, failed to demonstrate the existence of the Y Chromosome or the existence of distal Yq material translocated to another chromosome in the two patients. The Xg study in one of the patients and his family provided direct evidence of transmission of an X chromosome from father to son. We present indirect evidence favoring the mutation theory to explain the XX male phenotype.
Chromosomal mosaicism in amniotic fluid cell cultures
Authors: Sutherland Grant R. , Bowser‐Riley Susan M. , Bain A. Douglas
Published: July 2010

Six cases of chromosomal mosaicism detected in amniotic fluid cultures are described. In five of these there was no evidence of fetal mosaicism. In one case fetal mosaicism was demonstrated but only by the study of fibroblasts since blood cultures showed only normal cells. The implications of amniotic fluid mosaicism are discussed and it is concluded that this usually does not indicate fetal mosaicism. The value of repeated amnio‐centesis in the diagnosis of fetal mosaicism was demonstrated by findings in three of the cases. It is recommended that amniotic fluid cultures be harvested in situ for chromosome studies and that cytogenetic results be expressed as number of colonies karyotyped rather than as number of cells analyzed.
Serum esterases of Icelanders 1. A “silent” pseudocholinesterase gene in an icelandic family
Authors: Arnason Alfred , Jensson Olafur , Gudmundsson Sigurdur
Published: July 2010

During an investigation of cousin marriages in Iceland, five brothers and sisters were found to be hornozygous for the “silent” allele of plasma cholinesterase. Clinical information on two family members is presented and discussed, and the possibility of the presence of a “nearly silent” plasma esterase allele, in one of the family units investigated, is suggested.
The evaluation of infants with the Zellweger (cerebro‐hepato‐renal) syndrome*
Authors: Gilchrist Kennedy W. , Gilbert Enid F. , Shahidi Nasrollah T. , Opitz John M.
Published: July 2010

A brief overview of the clinicopathologic findings in the cerebro‐hepato‐renal syndrome of Zellweger (ZS) is presented. In order to understand more clearly the many diverse features of the ZS condition, a guideline is suggested for evaluation of a ZS infant in terms of physical features, family history, clinical pathophysiologic parameters, biopsy specimens, and postmortem procedures. The references provide rationale pertinent to the subject of discussion and/or furnish comments upon technical aspects for performance of analytical procedures.
Thin ribs in neonatal myotonic dystrophy
Authors: Fried K. , Pajewski M. , Mundel G. , Caspi E. , Spira R.
Published: July 2010

The recently described thin ribs seen in a neonate suffering from myotonic dystrophy represents a valuable sign for early detection of this condition. Thin ribs were found on chest radiographs of two siblings a short time after birth. This led in retrospect to the diagnosis of neonatal myotonic dystrophy. The diagnosis was confirmed by clinical and electromyographic data of myotonic dystrophy in the mother who was not previously known to have the disease. Both children died at the age of 2 days from respiratory distress. All children of affected mothers should have a chest radiograph soon after birth in order to help in diagnosis and to establish the frequency of this sign.
Free amino acids in extracts of cultured skin fibroblasts from patients with various amino acid metabolic disorders
Authors: Shih Vivian E. , Mandell Roseann , Levy Harvey L. , Littlefield John W.
Published: July 2010

In the search for a simple screening test for prenatal diagnosis of amino acid metabolic disorders, we compared the free amino acid contents in the extract of cultured skin fibroblasts from normal individuals with that from patients with 10 metabolic disorders: maple‐syrup urine disease; homocystinuria due to cystathionine synthase deficiency; homo‐cystinuria due to N5,10‐‐methylene‐tetrahydrofolate reductase deficiency; citrullinemia; argininosuccinic acidemia; propionic acidemia; hyperprolinemia Type II; non‐ketotic hyper‐glycinemia; hydroxyprolinemia; and hyperornithinemia. An accumulation of abnormal metabolites was not found in any of the disorders except argininosuccinic aciduria. Argininosuccinic acid anhydrides were detected in cell extracts from all four patients only after the extract was boiled at acid pH for 21/2 h. Thus, it is concluded that the measurement of free amino acids in extracts from cultured fibroblasts is not a useful screening technique in the diagnosis of inborn errors of amino acid metabolism.
Autosomal recessive syndrome of cerebellar ataxia and hypogonadotropic hypogonadism*
Authors: Neuhäuser Gerhard , Opitz John M.
Published: July 2010

An ataxia‐hypogonadism syndrome is reported in at least four of 15 family members (two brothers and two sisters). Consanguinity could be proven by genealogical studies; parents were second cousins. The onset of cerebellar ataxia in three sibs was at about 12–20 years, in the proposita at 33–38 years; progression was very slow. Hypogonadotropic hypogonadism was reflected in failure of maturation of secondary sexual characteristics, eunu‐choidism, absence of libido and infertility.

The concurrence of hereditary ataxia and hypogonadotropic hypogonadism is discussed and explained as pleiotropic effects caused by the homozygous state of a rare autosomal recessive gene. A review of the literature suggests that this is a previously undescribed disorder.
Absence of differences in platelet dihydroxyphenyIaIanine (DOPA) oxidase polymorphism in health and Duchenne's muscular dystrophy
Authors: Pacold Ivan , Morgan Julie , Cohen Louis
Published: July 2010

Extracts of platelets were subjected to vertical starch gel electrophoresis followed by enzyme staining to further investigate earlier reports of a unique dihydroxyphenylalanine (DOPA) oxidase polymorphism among boys with Duchenne's muscular dystrophy (DMD) and their mothers. This was said to be distinct from those found in healthy controls. Platelets were separated from citrated venous blood by differential centrifugation and checked for purity by phase contrast microscopy. The isolated platelets were disrupted by freeze‐thawing in Tris‐HC1 buffer (0.02M, pH 8.2), and the resulting platelet extracts were electrophoresed for 15 hours at 130V at 4°C. The starch gels were then sliced and stained with 0.2 % DOPA and 0.1 % MnCI2. Three electrophoretic patterns of DOPA oxidase activity were found in normal men and women: a single rapidly moving band; a single slowly moving band; and a broad band. These three patterns were also seen in boys with DMD, their mothers, and their fathers. Thus, a unique polymorphism was not found in boys with Duchenne's muscular dystrophy or their carrier mothers.
49, XXXXY patient with hemifacial microsomia
Authors: Kushnick Theodore , Colondrlllo Michael
Published: July 2010

An infant with the phenotype of hemifacial microsomia is presented. He was also found to have the karyotype of a sex chromosome abnormality.
A familial syndrome of central nervous system and ocular malformations
Authors: Chemke Juan , Czernobilsky Bernard , Mundel George , Barishak Y. Robert
Published: July 2010

A family is reported in which three of seven siblings were affected with an association of severe cerebral, cerebellar and ocular malformations. Brain malformations consisted of lissencephaly and the Dandy‐Walker anomaly; congenital cataracts, retinal dysgenesis and coloboma of the choroid were found in the eyes. The pathogenesis of these developmental anomalies is probably related to abnormal neuron migration and abnormal closure of fetal fissures, occurring at an early stage of embryonic development. The association of these malformations is unique, and may point to a new malformation syndrome, inherited as an autosomal recessive trait.
Early childhood development of four boys with 47, XXY karyotype
Authors: Puck Mary , Mnnes Katherine , Frankenburg William , Bryant Kathleen , Robinson Arthur
Published: July 2010

In an epidemiological study, infants identified at birth as having sex chromosome anomalies are enrolled in a voluntary, long term evaluation program. Case histories are presented of the first four boys in the series to have a 47, XXY karyotype. They have been followed from birth for 6 to 9 years, with physical and psychological evaluations. Parents were informed in general terms of the child's genetic defect, and were offered continuing support and encouragement throughout the study. Close cooperation with the families was maintained. So far, the development of all these children has fallen clearly within the normal range and a reasonable healthy developmental pattern has been secured. Minor deviations in motor, speech and emotional development suggest a common underlying pattern, but four cases are too few on which to establish a relationship between karyotype and phenotype. The data suggest that the symptomatology reported in selected children with a 47, XXY karyotype may be strongly dependent on factors other than the chromosomal constitution, and that an appropriate familial and environmental situation may minimize elevated risks due to the marked genetic defect.
Cultivated cells from diagnostic amniocentesis in second trimester pregnancies
Authors: Hoehn Holger , Bryant Eileen M. , Karp Lawrence E. , Martin George M.
Published: July 2010

From a total of 418 primary amniotic fluid colonies, 5.5 % were fibroblast‐like (F), 33.7 % epithelioid (E) and 60.8 % had characteristics of what was previously shown to be the principal class of clonable amniotic fluid cells (AF). Polyploidy occurred in all three categories, although both pure tetraploidy and mixoploidy were more frequent in E colonies. The incidence of non‐constitutional chromosomal changes was identical in AF and E type colonies if primary spreads were analyzed in situ without prior trypsinization. Spreads from pooled cell suspensions showed higher base‐line levels of both aneuploidy and structural changes. Analysis of individual colonies employing an in situ preparative technique is clearly the method of choice for a reliable cytogenetic prenatal diagnosis within the shortest possible period of time.
Associated congenital malformations in retinoblastoma
Authors: Bonaïti‐Pellié C. , Briard‐Guillemot M. L. , Feingold J. , Frézal J.
Published: July 2010

A complete family investigation was made for 598 cases of retinoblastoma and details of any associated congenital malformations were recorded. Associated malformations were found in seven cases, four of which were cleft palate. There was a highly significant difference between the frequency of cleft palate in our cases with retinoblastorna and the frequency in the general population.

This result supports the hypothesis that cases of retinoblastoma with associated congenital malformations are caused by germinal mutations.
Frequency of phenylketonuria in Norway
Authors: Saugstad Letten Fegersten
Published: July 2010

By January 1973, a total of 146 homozygotes (born between 1875 and 1972) for phenylketonuria (PKU) had been identified in Norway. This is an incomplete total, particularly in respect of PKU cases born before 1950, because of the PKU mortality rate.

Between 1951 and 1972, the observed incidence of PKU was unchanged at 0.07 ± 0.01 per 1000 live births. Haematological screening of about one‐third of all births in Norway between 1966 and 1972 indicated an incidence of 0.07 ± 0.02 per 1000 liveborn screened. As expected, this was well below the observed incidence of 0.11 ± 0.01 per 1090 from screening data from Denmark, and considerably higher than the observed value of 0.03 ± 0.01 per 1000 screened in Sweden.

In comparison, indirect estimates, using the inbreeding coefficient of parents of PKUs and that of the general population in Norway in the corresponding years (1874–1972), suggested a fall in incidence of PKU in Norway from 0.14 ± 0.15 per 1000 live births in 1918, to 0.08 ± 0.08 per 1000 in 1941, and to 0.06 ± 0.06 per 1000 live births in 1972.

The present level of inbreeding in Norway (obtained from the Medical Registration of Birth) is discussed and compared with information in the 1891 census, with the parish registers between 1889 and 1902, and with the parochial lists for the years 1903–1941.
AnthropologicaI significance of phenylketonuria
Authors: Saugstad Letten Fegersten
Published: July 2010

The highest incidence rates of phenylketonuria (PKU) have been observed in Ireland and Scotland. Parents heterozygous for PKU in Norway differ significantly from the general population in the Rhesus, Kell and PGM systems. The parents investigated showed an excess of Rh negative, Kell + and PGM type 1 individuals, which makes them similar to the present populations in Ireland and Scotland. It is postulated that the heterozygotes for PKU in Norway are descended from a completely assimilated sub‐population of Celtic origin, who came or were brought here, 1000 years ago. Bronze objects of Western European (Scottish, Irish) origin, found in Viking graves widely distributed in Norway, have been taken as evidence of Vikings returning with loot (including a number of Celts) from Western Viking settlements. The continuity of residence since the Viking age in most habitable parts of Norway, and what seems to be a nearly complete regional relationship between the sites where Viking graves contain Western imported objects and the birthplaces of grandparents of PKUs identified in Norway, lend further support to the hypothesis that the heterozygotes for PKU in Norway are descended from a completely assimilated subpopulation.

The remarkable resemblance between Iceland and Ireland, in respect of several genetic markers (including the Rhesus, PGM and Kell systems), is considered to be an expression of a similar proportion of people of Celtic origin in each of the two countries. Their identical, high incidence rates of PKU are regarded as further evidence of this. The significant decline in the incidence of PKU when one passes from Ireland, Scotland and Iceland, to Denmark and on to Norway and Sweden, is therefore explained as being related to a reduction in the proportion of inhabitants of Celtic extraction in the respective populations.
Vitiligo and dysgammaglobulinemia. A case report and family study
Authors: Bader Patricia I. , Biegel Angenieta , Epinette Warren W. , Nance Walter E.
Published: July 2010

This report concerns an 8 year old female with vitiligo and a dysgammaglobulinemia characterized by absent IgA, very low IgG, and normal TgM. The t‐cell immune system was intact but other family members had low levels or absence of IgA. The possible relationship of dysgammaglobulinemia and vitiligo is discussed along with the classification and inheritance of the immune cell defects.
Serum alkaline phosphatase in patients with multiple sclerosis
Authors: Papiha S. S. , Roberts D. F.
Published: July 2010

Sera from multiple sclerosis patients show a deficit of intestinal alkaline phosphatase (serum type Pp2) by comparison with normal sera. This is not due to variation in ABO frequency, since the specimens from patients and normals are matched for ABO frequency, and it is not due to differences in secretor frequency, but represents a real dificit for Pp2 in patients with multiple sclerosis, particularly noticeable in group 0 individuals.
The effect of structural aberrations of the chromosomes on reproductive fitness in man
Authors: Morton Newton E. , Jacobs Patricia A. , Frackiewicz Anna , Law Pamela , Hilditch C. Judith
Published: July 2010

Methods are presented to estimate relative fitness of carriers as a function of fertility, survival, and generation time in pedigrees under incomplete ascertainment. A large sample of diverse chromosomal aberrations reveals significant effects on all three parameters, giving a relative fitness of .769 ± .039. There is no significant shift in segregation frequency. Implications of these results for population dynamics of structural rearrangements are discussed. The following paper applies these methods to specific classes of aberrations.