bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudomosaicism in prenatal diagnosis: Two simultaneous, independent reciprocal translocations
Authors: Cohen Maimon M. , Balkin Nancy E.
Published: June 2005

Cytogenetic evaluation of cultured amniotic fluid cells showed mosaicism of three karyotypes: 46, XY; 46, XY [t(13;17)(q13;q25)]; and 46, XY [t(11;12)(p11;q13)]. Reanalysis of cells from the four original culture flasks harvested individually revealed that both translocations derived from the same flask. Repeat amniocentesis, as well as peripheral blood obtained postnatally from a phenotypically normal male infant, demonstrated only normal chromosomes (46,XY). This observation represents a case of pseudomosaicism containing two different reciprocal translocations.
GENTIC: A computerized medical genetic case record system
Authors: Aymé Ségolène , Aurran Yvette , Gouvernet J. , Mattei J.‐F. , Giraud F. , Opitz John M.
Published: June 2005

GENTIC is a computerized system for the storage, recall, and analysis of data collected by the Medical Genetics Center in Marseille, France. It is based on a standard case report file that includes a full clinical description of all patients, results of cytogenetic investigations, and details of the genetic counseling provided. GENTIC has been used since 1975, and data on more than 5,000 families are accessible for study. This system has improved the quality of consultations, follow‐up, and research. It provides data for epidemiological studies and for syndrome identification. This system is maintained at an annual cost of $3,000, salary costs not included, after an initial investment of $40,000.
Autosomal mosaicism in amniotic fluid cells from a twin pregnancy
Authors: Greenberg Frank , Elsas Nancy T. , Reidy John A. , Chen Andrew T. L. , Stone Lawrence B. , Opitz John M. , Daniel Art , Hecht Frederick
Published: June 2005

Amniocentesis was performed on a 39‐year‐old gravida 4 woman because of maternal age. Ultrasonography demonstrated a twin pregnancy, and two amniotic fluid specimens were obtained under direct ultrasound guidance. All cells analyzed from the first specimen were 46,XX. In the second specimen, one colony in each of two flasks had trisomy 9; the remaining 3 colonies analyzed were 46, XX. The total cell count in the second specimen was 14 (24%) of 58 cells which were trisomic for chromosome 9. The parents elected to continue the pregnancy, which resulted in two live‐born infants, a male and a female, both chromosomally normal. The most likely explanation for the amniotic fluid finding is that fluid from one sac was sampled twice and that trisomic cells from the amnion were obtained during the second tap.
Monozygotic twins discordant for trisomy 21
Authors: Rogers John G. , Voullaire Lucille , Gold Hugo , Opitz John M.
Published: June 2005

Monochorionic twins were phenotypically discordant for Down syndrome. Chromosome analysis of lymphocytes showed both to be mosaics. Fibroblast chromosome analysis showed that one twin was 46,XY and the other 47,XY, +21. Blood mosaicism appears to have resulted from placental anastomoses. The twins are presumed to be monozygotic on the basis of placentation, identical blood groups, HLA haplotypes, and serum proteins. We offer some speculation on the manner of occurrence of this rare event.
Aplasia cutis congenita in two sibs discordant for pylori atresia
Authors: Carmi R. , Sofer S. , Karplus M. , Ben‐Yakar Y. , Mahler D. , Zirkin H. , Bar‐Ziv J. , Opitz John M.
Published: June 2005

We report two sibs who were the products of a consanguineous mating, and who had an extensive form of aplasia cutis congenita (ACC). In one of them the generalized skin disorder was manifested by slipping off of the epidermis and mucous membranes with the slightest trauma. This sib also had pyloric atresia and other congenital malformations. Two hypotheses are presented to explain the discordance between the siblings for the abnormalities other than the ACC. One hypothesis assumes varying degrees of severity of the same autosomal recessive disease. The second suggests linkage between the gene for ACC and the gene for an epidermolysis bullosa (EB)‐like disorder and pyloric atresia. A recombination event involving the EB‐pyloric atresia gene in one carrier parent would then lead to an offspring with only ACC. Prenatal diagnosis is suggested by monitoring α‐fetoprotein levels in amniotic fluid.
The HLAB* 18,BF* F1 in haplotype in type 1 diabetes
Authors: Walsh Linda J. , Cox Diane Wilson , Ehrlich Robert M. , Opitz John M.
Published: June 2005

We have investigated the properdin factor B (BF) locus as a possible marker for Type 1 diabetes. The frequencies of the four BF alleles were determined among 70 Type 1 diabetics with onset before age 18 years. The frequency of BF F1 among the diabetics was increased compared with 206 controls (15.7 vs 3.4%). The relative risk (RR) associated with BF F1 was 5.30. The suggestion that BF F1 is most strongly associated with onset of diabetes under 10 years of age was not supported. HLAB 18 was increased (RR = 4.91) and B 7 was decreased in frequency (RR = 0.41) among the 62 diabetics tested compared with 238 controls. An association was observed between HLAB 18 and BF F1 among the diabetics. A study of 12 families in which BF*F1 was segregating suggested that BF*F1 and HLAB*18 are components of a haplotype associated with Type 1 diabetes in this population and that both haplotypes of an affected parent may contribute to the development of Type 1 diabetes.
The conditions manifesting taurodontism
Authors: Jorgenson Ronald J.
Published: June 2005

Taurodontism is a trait that has captured the interests of evolutionists and clinical geneticists. This paper reviews the reported cases of taurodontism as an isolated trait and as a component of malformation syndromes. Because of the nature of the syndromes with which it is associated and its frequency in the general population, it is concluded that taurodontism is the result of an ectodermal defect and may be useful as an indicator of development instability.
Duplication (5p13→pter): Prenatal diagnosis and review of the literature
Authors: Khodr Gabriel S. , Cadena Gary , Le Kim Loan , Kagan‐Hallet Kathleen S.
Published: June 2005

We describe a patient with a reciprocal translocation t(5,13) and her three offspring. The chromosome anomaly was ascertained after the birth of her first child, who had the cri‐du‐chat syndrome. Amniocentesis demonstrated the presence of a dup(5p). The anomalies affecting that fetus are described and compared with the reported phenotypes of dup(5p). The extent of clinical findings in the reported cases depends on the length of the duplicated portion. The larger the duplication (p11→pter), the more pronounced are the clinical signs. Physical signs are nearly absent when 5p14→ter is involved. Also, translocations affecting chromosome 5 have an increased abnormal outcome when compared to D/D Robertsonian translocations. This is the first instance of antenatal diagnosis of trisomy 5p.
A maximum likelihood test of the two locus model for coeliac disease
Authors: Greenberg David A. , Lange Kenneth L. , Opitz John M.
Published: June 2005

A segregation analysis of two‐locus inheritance based on a maximum likelihood test is developed and applied to coeliac disease. The results clearly reject a dominant‐recessive mode of inheritance, but do not reject a double recessive model. In addition, analysis of the available affected sib pair HLA data are shown to be inconsistent with simple (single‐locus) dominant or recessive models with environ‐mentally‐caused reduced penetrance.
3:1 Meiotic disjunction in a mother with a balanced translocation, 46,XX,t(5,14)(p15;q13) resulting in tertiary trisomy and tertiary monosomy offspring
Authors: Abeliovich Dvorah , Yagupsky Pablo , Bashan Nava , Opitz John M.
Published: June 2005

We describe the family of a balanced translocation carrier mother with the karyotype 46,XX,t(5,14)(p15,q13). In two of her five children 1:3 segregation occurred, resulting in del (14q) and dup (14q). The propositus with the dup (14q) has some of the typical manifestations of this syndrome and coloboma of the iris O.U.
Brief cytogenetic case report: A 4.5‐year‐old girl with deletion 4q syndrome — de novo, 46,XX, del(4) (pter→q31:)
Authors: Young Robert S. , Palmer Catherine G. , Bender Harvey A. , Weaver David D. , Hodes M. E. , Opitz John M.
Published: June 2005

A 3.5‐year‐old white girl had growth and mental retardation of prenatal origin, unusual facial appearance, cleft palate, abnormal sternum, absence or hypoplasia of some digits, diaphragmatic hernia, ventricular septal defect, and rib and vertebral anomalies. Her karyotype was 46,XX,del(4)(pter→q31:).
Peyronie's disease: A newly recognized autosomal‐dominant trait
Authors: Bias Wilma B. , Nyberg Leroy M. , Hochberg Marc C. , Walsh Patrick C. , Opitz John M.
Published: June 2005

Peyronie's disease, a connective tissue disorder of unknown cause, is characterized by the formation of thickened fibrous plaques on the dorsum of the penis. It often occurs simultaneously with other fibrotic changes, most notably Dupuytren's contracture of the hands or feet. There are no previous reports suggesting inheritance of this syndrome; however, Willscher et al reported an association between Peyronie's disease and antigens of the HLA‐B7 cross‐reacting group.

Family studies were undertaken when three patients reported similarly affected first‐degree relatives. One kindred showed father‐to‐son transmission of Peyronie's disease with Dupuytren's contracture in three generations. Pedigree analysis of the three families suggests that Peyronie's syndrome is a male‐limited, automosal‐dominant trait. Antigens of the HLA‐B7 cross‐reacting group occurred in all three kindreds; however, the data ruled out close linkage of the disease and HLA.
Lymphocyte capping in limb‐girdle muscular dystrophy: Patients and carriers in an amish isolate
Authors: Bader Patricia I. , Bender Cynthia J. , Creason Marilyn T. , Conn Patricia S. , Townsend Douglas W.
Published: June 2005

We observed a decreased proportion of capped lymphocytes using polyvalent immunoglobulin and concanavalin‐A as ligands in limb‐girdle muscular dystrophy patients, obligate carriers, and individuals who are at‐risk for being limb‐girdle muscular dystrophy carriers. Using the proportion of capped cells as a parameter, we found there was overlap between the carrier and control range. However, we were able to estimate the risk of being a carrier in the Amish who have an increased prevalence of the limb‐girdle muscular dystrophy gene.
An anthropometric study of girls with the Ullrich‐Turner syndrome
Authors: Ikeda Yukie , Higurashi Makoto , Egi Shinzo , Ohzeki Norihiko , Hoshina Hiroki
Published: June 2005

Anthropometric measurements were made on 11 Japanese girls with Ullrich‐Turner syndrome (UTS) from 8 months to 14 years. Height, lower limb length, and upper limb length of the UTS patients was less than that of normal control girls. Conversely, chest circumference, transverse chest diameter, and chest depth of UTS girls was well developed and equal to that of the control girls. Measurement results of head (head circumference, head length, and head breadth) and face (bi‐zygomatic breadth, internal bi‐ocular breadth and morphological face height) of the UTS patients were similar to those of normal girls. Bi‐acromial breadth and bi‐iliac diameter in the UTS were normal.
Familial occurrence of hemifacial microsomia with radial limb defects
Authors: Moeschler John , Clarren Sterling K. , Opitz John M.
Published: June 2005

Usually hemifacial microsomia is an isolated malformation complex; however, it may be associated with other malformations as in Goldenhar syndrome. This report describes three patients with hemifacial microsomia and radial limb deficiency. This may represent a specific autosomal‐dominant condition.
Genetic study of a family with two members with weber christian disease (panniculitis) and alpha 1 antitrypsin deficiency
Authors: Clark Peggy , Breit S. N. , Dawkins R. L. , Penny R. , Opitz John M.
Published: June 2005

Alpha 1 antitrypsin phenotypes and serum levels are presented for a family in which two brothers have Weber Christian disease and α1 antitrypsin (PI) Z phenotypes. Clinical histories are described for these two men. A younger brother has the PI Z phenotype but does not have the disease, indicating that additional genetic and/or environmental factors contribute to the pathogenesis of Weber Christian disease. However, the two cases described provide additional evidence for a relationship between α 1 antitrypsin deficiency and the development of symptoms.
An autosomal dominant syndrome of radial hypoplasia, triphalangeal thumbs, hypospadias, and maxillary diastema
Authors: Schmitt Edward , Gillenwater Jay Y. , Kelly Thaddeus E. , Opitz John M.
Published: June 2005

We describe a family in which eight persons (three males, five females) in three generations had a syndrome of bilateral and strikingly symmetrical triphalangeal thumbs and radial hypoplasia. The affected males also had a first‐degree hypospadias and all affected family members had an anterior maxillary diastema. The syndrome was inherited in an autosomal dominant fashion.
H‐Y antigen expression in patients with X‐autosomal translocations and gonadal dysgenesis
Authors: Haseltine Florence P. , Lynch Vincent A. , Van Dyke Daniel L. , Breg W. Roy , Francke Uta , Opitz John M.
Published: June 2005

Cells from three patients with early gonadal failure and a balanced reciprocal translocation involving the long arm of the X chromosome and an autosome were studied. Fibroblasts from a patient with a similar balanced reciprocal translocation but normal reproductive capabilities were also studied. Two of the four patients were found to have serologically detectable H‐Y antigen on their cells. Since H‐Y antigen has been found on the cells of other patients with X chromosome abnormalities but without a Y chromosome, it is thought that the X chromosome plays a role in the regulation of H‐Y antigen expression. This study suggests that the long arm of the X chromosome may be involved but the location of a regulatory gene cannot be identified in these studies. These cases do not permit us to implicate H‐Y antigen as a cause of gonadal dysgenesis and early gonadal failure in females who have structurally abnormal X chromosomes.
Pyruvate‐kinase (PK) and creatine‐kinase (CK) in normal pregnancy and its implication in genetic counseling of duchenne muscular dystrophy (DMD)
Authors: Zatz Mayana , Karp L. E. , Rogatko A. , Opitz John M.
Published: June 2005

The activities of pyruvate‐kinase (PK) and creatine‐kinase (CK) were measured in 50 normal pregnant women in both serum and amniotic fluid. Serum PK activity was found to be significantly higher in pregnant than in nonpregnant women, while serum CK did not differ significantly between the two population samples. In amniotic fluid, very little or no PK or CK activity was found. However, the mean PK activity in amniotic fluid obtained from women carrying male fetuses was significantly higher than in those carrying female fetuses. At the present time, it is concluded that if a woman at risk for having a son with Duchenne dystrophy is seeking genetic counseling when already pregnant her serum PK or CK should be compared with that of normal female pregnant controls. It is also suggested that determination of pyruvate‐kinase in fetal blood might be used in addition to CK for prenatal diagnosis of Duchenne muscular dystrophy.
Familial omphalocele: Analysis of risk factors and case report
Authors: Diliberti John H. , Opitz John M.
Published: June 2005

This is a report of a family with recurrence of omphalocele and apparent autosomal dominant transmission of abdominal wall hernias. Reported cases of familial omphalocele are reviewed and analyzed for risk factors. Familial cases are rarely associated with structural anomalies outside the gastrointestinal tract but often demonstrate vertical transmission that suggests that in certain families omphalocele is due to an autosomal dominant mutation.
Improved detection of Duchenne muscular dystrophy heterozygotes using discriminant analysis of creatine kinase levels
Authors: Muir W. A. , Knoke J. , Martin A. , Vignos P. , McErlean A. , Opitz John M.
Published: June 2005

We have assessed the sensitivity and specificity of tests to detect carriers of Duchenne muscular dystrophy by use of three serum enzymes (creatine kinase, pyruvate kinase, and aldolase) and discriminant analysis in 21 obligate heterozygotes and 28 normal controls. We found no significant age effects on enzyme levels. Each enzyme level considered separately was significantly higher in heterozygotes. Use of logs improved discrimination, and log CK was sufficient by itself as a discriminant (that is, addition of other enzymes did not significantly improve discrimination). We present procedures to generate posteriori probabilities for genetic counselling that incorporate prior probabilities and enzyme levels. Our results show both improved sensitivity (90%) and specificity (86%).
A new syndrome of hemangiomatous branchial clefts, lip pseudoclefts, and unusual facial appearance
Authors: Hall Bryan D. , Delorimier Alfred , Foster L. H. , Opitz John M.
Published: June 2005

Two unrelated children (one male, the other female) had unusual craniofacial anomalies consisting of hemangiomatous branchial clefts, lip pseudoclefts, and identical unusual facial appearance. One also had unilateral microphthalmia and both had congenital nasolacrimal duct obstruction. Two similar, sporadic cases from the literature were also identified. These four cases form the basis of a new, distinctly recognizable pattern of malformation.
CNS malformations in the kraków region. I. Birth prevalence and seasonal incidence during 1979–1981
Authors: Pietrzyk Jacek J. , Grochowski Jan , Kańska Barbara , Opitz John M.
Published: June 2005

The birth prevalence of CNS malformations in the region of Krakow from 1979 to 1981 was determined to be 1.26/1000 from records of all live‐ and still‐birth deliveries. The frequency of anencephaly was 0.23/1,000; spina bifida and encephalocele, 0.70/1000; isolated hydrocephaly, 0.26/1,000; and other CNS anomalies, 0.06/1,000. The observed rates are below the median European level.

Female preponderance was found among the probands with anencephaly, encephalomeningocele, and myelomeningocele.

Cytogenetic examination of 35 newborns with CNS malformations documented normal karyotypes in all neonates.

The analysis of seasonal distribution of proband's birthdate and of date of mother's last menstrual period showed no significant seasonal trend.
Identical multiple congenital anomalies/mental retardation (MCA/MR) syndrome due to del(2)(q32) in two sisters with intrachromosomal insertional translocation in their father
Authors: Pai G. S. , Rogers J. Felix , Sommer Annemarie , Opitz John M.
Published: June 2005

We report two sisters with a deficiency of band 2q32 that resulted from meiotic crossover events in their father, who is a balanced, intrachromosomal insertional translocation heterozygote. This three‐break rearrangement involving a single chromosome is among the rarest class of human structural chromosome abnormalities. A review confirms the theoretically predicted high risk of unbalanced progeny for such translocation heterozygotes. Fertility of carriers seems to be unimpaired in either sex. Available information is insufficient to define the effect of insertional translocation on homologue pairing, crossover frequency, and other meiotic phenomena.
Down syndrome—a disruption of homeostasis
Authors: Shapiro Burton L. , Hermann J. , Opitz J. M.
Published: June 2005

A major question in human genetics concerns the relationship between the extra chromosome material in the Down syndrome (DS) and its effects. It is suggested here that a generalized disruption of evolved genetic balance in cells of affected individuals leads to decreased developmental and physiological buffering against genetic and environmental forces. Examples of consequences in DS of this model of disruption of homeostasis are presented: (i) increased variance for metric traits, (ii) amplified instability of developmental pathways, (iii) reduced precision of physiological homeostatic controls, and (iv) generalized increased morbidity. Evolution has selected for interacting systems. When this evolved balance is disrupted, as in autosomal aneuploidy, the organism is generally disrupted. The model emphasizes the role of environment in producing much of the DS phenotype. Traits less buffered than others in the general population are the ones most disturbed in DS and account for much of the DS phenotype.
Prenatal diagnosis of perinatally lethal osteogenesis imperfecta
Authors: Elejalde B. Rafael , de Elejalde Maria Mercedes , Opitz John M.
Published: June 2005

Prenatal diagnosis of osteogenesis imperfecta was achieved at 17 weeks of gestation using ultrasound through recognition of low echogenic properties of all the bones, abnormally shaped skull, bell‐shaped rib cage, distally thinned ribs, short and deformed long bones, wide metaphyses, and thin diaphyses. Severely limited abnormal movements, abnormal positioning of the lower limbs also were typical of the condition. The recognition of the signs reported in this paper will allow the identification of the condition in utero in the second trimester.
Cranial defects in the Goldenhar syndrome
Authors: Wilson Golder N. , Herrmann Jürgen , Opitz John M.
Published: June 2005

Four patients are presented with the Goldenhar syndrome (GS) and cranial defects consisting of plagiocephaly, microcephaly, skull defects, or intracranial dermoid cysts. Twelve cases from the literature add hydrocephalus, encephalocele, and arhinencephaly to a growing list of brain anomalies in GS. As a group, these patients emphasize the variability of GS and the increased risk for developmental retardation with multiple, severe, or unusual manifestations. The temporal relation of proposed teratogenic events in GS provides an opportunity to reconstruct biological relationships within the 3–5‐week human embryo.
Hereditary lecithin‐cholesterol acyltransferase deficiency and bloom syndrome in the same individual
Authors: Shojania A. M. , McAlpine P. J. , Ray M. , Opitz John M.
Published: June 2005

A couple who were first cousins had three children: an older son with Bloom syndrome (BLS) and homozygous lecithin‐cholesterol acyltransferase (LCAT) deficiency; the second child (a son) and the parents are LCAT deficiency heterozygotes; and the youngest child (a daughter), is homozygous for LCAT deficiency. The use of genetic markers gave no evidence of linkage of BLS and LCAT loci.
Chromosome heteromorphism analysis in cases of disputed paternity
Authors: Olson Susan B. , Magenis R. Ellen , Rowe Shirley I. , Lovrien Everett W. , Opitz John M.
Published: June 2005

Blood test results, using standard procedures, failed to exclude the alleged father as the biological father of a child in a case of disputed paternity. Using 21 different systems, the probability of exclusion for the man was 98.19%, and the probability of paternity was only 93.90% with a paternity index of 15.48. Chromosome heteromorphisms of all three individuals were studied. By comparison of fluorescent markers of chromosomes 13, 14, 15, 21, and 22, the child was shown to inherit one homologue of each of these chromosomes from the mother, but none were like the heteromorphisms of the alleged father. This excluded him as the biological father.
Trichoodontoonychial dysplasia—a new meso‐ectodermal dysplasia
Authors: Pinheiro Marta , Freire‐Maia Newton , Roth Alcyone J. , Opitz John M.
Published: June 2005

We describe a hitherto apparently undescribed ectodermal dysplasia in four siblings. The condition combines severe hypotrichosis, hypoplasia of enamel leading to secondary anodontia, dystrophic nails, supernumerary nipples, nevus pigmentosus, bone deficiency of the fronto‐parietal region, and other anomalies. This condition is probably due to an autosomal‐recessive gene.
Cebocephaly‐holoprosencephaly in a newborn girl with a terminal 7q deletion [46,XX,del(7)(pter→q32:)]
Authors: Schwartz Stuart , Meekins Joann , Panny Susan R. , Sun Chen‐Chih J. , Cohen Maimon M. , Opitz John M.
Published: June 2005

Cytogenetic study of a day‐old infant showed a terminal del(7q): 46,XX,del(7)(pter→q32:). This infant had cebocephaly with holoprosencephaly. These clinical findings are atypical for the 7q – syndrome, in which patients usually have growth and mental retardation with few facial abnormalities.
Self‐limited autosomal recessive syndrome of skin ulceration, arthroosteolysis with pseudoacromegaly, keratitis, and oligodontia in a Kirghizian family
Authors: Kozlova S. I. , Altshuler B. A. , Kravchenko V. L. , Opitz John M.
Published: June 2005

We report on a previously apparently undescribed Puretic syndrome‐like self‐limited autosomal recessive disorder with onset in infancy and running its course by 11 yr in five sibs in a Kirghizian family with recurrent skin ulceration, arthralgias, fever, fistulous osteolysis around joints, oligodontia, nail dystrophy and keratitis with visual impairment or blindess in three of the five affected sibs. Affected hands and feet acquire a pseudoacromegalic appearance; fingers become clawed; involvement of growth plates around knees may lead to asymmetrical shortness with secondary scoliosis.

Slow but normal healing during and after the course of the disease leaves severe cicatrization and chronic arthroses. No other organ system is involved, intellect is normal, and health and reproductive capacity are otherwise unimpaired. We propose the name Kirghizian dermatoosteolysis for this condition.
Duplication 18q syndrome
Authors: Ehrlich Sonia , Bustos Tania , Paika Inder J. , Milunsky Aubrey , Opitz John M.
Published: June 2005

Some variation in the phenotype of patients with dup(18q) is recognized. Our patient has the phenotype described for dup(18qter).
Biochemical defect of non‐keratan‐sulfate‐excreting Morquio syndrome
Authors: Fujimoto Atsuko , Horwitz Allen L. , Opitz John M.
Published: June 2005

Two children of second‐cousin parents were found to have a very mild form of Morquio syndrome. The 14‐year‐old boy was 147 cm tall and had fine corneal deposits, a broad chest, dislocated hips, and flat feet. His 7‐year‐old sister had a broad chest but otherwise normal physical development. An abnormal lumbar spine was seen in radiographs of both children. Analysis of the urine from the affected children showed levels of acid mucopolysaccharides (AMPS) up to twice as high as that found in normal urine, but no evidence of keratosulfaturia. Most urinary AMPS was chondroitin‐6‐sulfate. Multiple assays of N‐acetylgalactos‐amine‐6‐sulfate (GalNAc‐6‐SO4) sulfatase in leukocytes and cultured skin fibroblasts showed deficiency of this enzyme in the range found in the classical form of Morquio (Morquio A) syndrome. This report identifies an enzymatic defect in one form of non‐keratan‐sulfate‐excreting Morquio (NKSE Morquio) syndrome and confirms the absence of keratosulfaturia in this mild form of Morquio disease.
Pedigree discriminant analysis: A method to identify monogenic segregation
Authors: Zlotnik L. H. , Elston R. C. , Namboodiri K. K.
Published: June 2005

We describe a method for obtaining a linear discriminant function to identify monogenic segregation in multivariate pedigree data. It differs from Fisher's linear discriminant function in that it does not assume that the genotype of each individual in the pedigree already known. The method consists of finding that linear function of the variables that maximizes the likelihood of a set of pedigree data, under the hypothesis of single gene segregation, subject to the constraint that the total sample variance of the function remains constant. To simplify the computation the variables are first transformed to their standardized principal components. Reanalysis of a set of pedigree data suggests that age and powers of age should be considered as extra variables from which the principal components are obtained, and virtually all of the variance should be accounted for by the principal components used to obtain the discriminant function.
The impact of the federal cutback on genetic services
Authors: Holtzman Neil A. , Opitz John M.
Published: June 2005

A survey of directors of federally supported genetics, sickle cell and hemophilia programs was undertaken to determine the effect of reduced federal awards for fiscal year 1983 (FY83). Most states deemed ineligible for federal genetics and sickle cell grants for FY83 were unable to make up federal losses with funds from other sources. In FY82, per capita allocations to genetics and sickle cell programs were not significantly different between states that remained eligible in FY83 and those that became ineligible. In FY83, however, per capita allocations were significantly lower in the ineligible states. If cutbacks were to curtail operations, most program directors would give their highest priority to preserving newborn screening and follow‐up services. Of the 23 states that do not currently charge for newborn screening, 8 are contemplating imposition of a charge. The findings suggest that continued or expanded availability of genetic services depends, in part, on federal support.
Waardenburg syndrome—penetrance of major signs
Authors: Preus M. , Linstrom C. , Polomeno R. C. , Milot J.
Published: June 2005

We have estimated that 83% of individuals carrying the gene for Waardenburg syndrome type I show penetrance of the gene as measured by dystopia canthorum. This is lower than previous estimates, which failed to consider the frequency of equivocal dystopia in the general population. The addition of three other major signs (hearing loss, white forelock, and premature graying of the hair or vitiligo) does not substantially increase the discrimination of gene carriers (85% versus 83%). We estimate that about 75% of the first‐degree relatives of probands can be assigned as normal or a gene carrier on the basis of the four major signs.
Variable phenotype associated with duplication of different regions of 2p
Authors: Fineman Robert M. , Buyse Marylou , Morgan Martha
Published: June 2005

Previous reports suggest that duplication of the distal part of 2p causes a distinct syndrome. Of the 20 published cases, all resulted from a parental translocation. We report here clinical and cytogenetic data on three patients with dup(2p) and few, if any, of the physical findings of the syndrome. Our data suggest that dup(2p) is associated with an extremely variable phenotype which may be quite mild in some cases. It is also possible that many of the nonspecific developmental anomalies thought to be part of the syndrome may be caused by the accompanying deletion.
Screening of mentally retarded males for macro‐orchidism and the fragile X chromosome
Authors: Howard‐Peebles Patricia N. , Finley Wayne H. , Opitz John M.
Published: June 2005

Four hundred forty‐four male residents of a state mental retardation institution were screened for macro‐orchidism. Twenty‐six white males (8.3%) and two black males (1.5%) had marked macro‐orchidism (>34 ml). Seven of 17 whites tested for the fragile X were positive; the one black tested was negative. Thus, a minimum of 7/26 or 27% (whites) are fragile X positive indicating potential population variability, also evident from previous reports. Concurrent testing of institutionalized brother pairs indicated over half of the fragile X‐positive males had a strong family history consistent with X‐linked mental retardation.
The oto‐palato‐digital syndrome, proposed type II
Authors: Fitch N. , Jequier S. , Gorlin R. , Opitz John M.
Published: June 2005

We present a follow‐up of the infant with oral, cranial, facial, and limb abnormalities described by us in 1976. Since then, several other very similar cases have been reported. We propose that this syndrome be called the oto‐palato‐digital syndrome, type II.
Probable autosomal recessive inheritance of polysplenia, situs inversus and cardiac defects in an Amish family
Authors: Arnold G. L. , Bixler D. , Girod D.
Published: June 2005

We report on an Amish family with five individuals in two generations with complex congenital heart disease. Autopsy findings in one and clinical examination in the others support the diagnosis of polysplenia “syndrome.” In a mouse model, this spectrum of situs abnormalities and cardiovascular defects shows recessive inheritance with homozygotes having either situs solitus or situs inversus or ambiguous situs. The parents of the four affected sibs are fourth cousins. We think that the father of these four children is an affected but clinically normal homozygote, that his deceased sister was an affected homozygote, and it seems likely that they too had consanguinous parents.
Parents' adaptation to early diagnosis of sex chromosome anomalies
Authors: Puck Mary H. , Bender Bruce G. , Borelli Joyce B. , Salbenblatt James A. , Robinson Arthur , Opitz John M.
Published: June 2005

In 56 structured psychiatric interviews parents were asked to describe their experience as participants in the Denver prospective study of children with sex chromosome anomalies in order to assess its impact on attitudes toward the identified child and on family relationships. It was found that most achieved satisfactory understanding of the diagnosis with minimal disturbance, preferred early disclosure, denied its influence on parent‐child and parent‐parent relationships, and were reasonably comfortable in sharing diagnostic information with the child. Environmental and cultural factors did not correlate with the responses obtained. Emphasis directed toward obstacles in the adaptive process permitted evaluation of reported parental anxieties arising from faulty or delayed communication of the diagnosis, a child's adjustment to problems of growth and development, and, for parents of children with 45,X and 47,XXY chromosome constitutions, anxiety regarding anticipated difficulty in sexual maturation and fertility. The assessment interviews afforded additional opportunity for clinical discussion and counseling with parents on issues of concern to them.
Trisomy 18/trisomy 13 mosaicism in an adult with profound mental retardation and multiple malformations
Authors: Wilson William G. , Shires Mary Ann , Willson Kathy A. , Wyandt Herman E. , Harris Linda M. , Kelly Thaddeus E.
Published: June 2005

We report on an adult woman with profound mental retardation and multiple anomalies who consists of 3 cell lines: one with trisomy 18, one with trisomy 13, and a normal cell line. Her phenotype includes manifestations of both trisomy syndromes. The origin of these cell lines could have been a doubly aneuploid (48,XX+ 13, + 18) or singly aneuploid (47,XX + 18 or 47,XX, + 13) zygote with subsequent mitotic nondisjunctions, or a normal zygote with multiple mitotic nondisjunctions. There have been four previous reports of mosaicism involving both trisomy D and trisomy E; all died in the first six months of life. Two of these cases had a doubly aneuploid (48,XX, + D + E) cell line. Our patient illustrates the need for study of several tissues in patients with complex aneuploidy syndromes or atypical manifestations of a given syndrome (such as prolonged survival), as well as the need for caution in counseling families about prognosis for survival in autosomal trisomies which usually are lethal.
Electron spin resonance spin label studies of the erythrocyte membrane in Duchenne muscular dystrophy
Authors: Clark A. D. , Nash G. B. , Patel K. J. , Wyard S. J. , Opitz John M.
Published: June 2005

The membrane organisation of erythrocytes from patients with Duchenne muscular dystrophy (DMD) and from asymptomatic carriers was studied by the electron spin resonance (ESR) spin label technique. Following the work of Sato et al [1978], we used 2‐(14‐carboxytetradecyl)‐2‐ethyl‐4, 4‐dimethyl‐3‐oxazolidinyloxyl as probe. We found no significant difference in lipid fluidity at 30°C, measured by the ratio of the line height at central field to that at high field ho/h−1, in DMD patients or carriers compared to appropriate control persons. Our conclusions for the dystrophic boys differ from those of Sato et al [1978], although our data are consistent with theirs within experimental error.

We also studied the variation of the ratio ho/h−1 over the temperature range 5–35°C in these individuals. For normal erythrocytes there is a discontinuity in this plot around 15°C that is absent in the erythrocytes of DMD patients [in agreement with the findings of Sato et al, 1978] and also absent in DMD carriers. We suggest the slope of this logarithmic temperature plot over the range 15–35°C is a more useful empirical parameter as the presence of these discontinuities is sometimes uncertain, and using this parameter, we find a clear separation between carriers and controls.
The Weissenbacher‐Zweymüller, Stickler, and Marshall syndromes: Further evidence for their identity
Authors: Winter Robin M. , Baraitser Michael , Laurence K. M. , Donnai Dian , Hall Christine M. , Opitz John M.
Published: June 2005

We report on three unrelated children with neonatal radiological characteristics of the Weissenbacher‐Zweymüller (W‐Z) syndrome. Subsequently, they developed the Marshall syndrome. The relationship between the W‐Z, Marshall, and Stickler syndromes is discussed.
The Pena‐Shokeir syndrome: Report of five cases and further delineation of the syndrome
Authors: Chen H. , Blumberg B. , Immken L. , Lachman R. , Rightmire D. , Fowler M. , Bachman R. , Beemer F. A.
Published: June 2005

We report on five cases of lethal Pena‐Shokeir syndrome from three families with affected sibs. In addition to multiple anklyoses, camptodactyly, facial anomalies, and pulmonary hypoplasia, one fetus had pterygia of the neck and axillae and cardiac hypoplasia. Radiographic changes are nonspecific and probably are related to a lack of intrauterine movement. Our data and review of the literature suggest that pterygium formation is one of the manifestations of the Pana‐Shokeir syndrome. A recently described lethal form of the recessively inherited multiple pterygium syndrome may represent a severe form of the Pena‐Shokeir syndrome.
Enhancement of a fra(16)(q22) with distamycin A: A family ascertained through an abnormal proposita
Authors: Dunner Jennifer A. , Martin Alice O. , Traisman Edward S. , Traisman Howard S. , Elias Sherman , Opitz John M.
Published: June 2005

A family in which a fragile site at 16q22 was segregating was ascertained through a newborn infant with multiple anomalies. The same fragile site was present in the phenotypically normal father and in a brother with cleft palate. The fra(16)(q22) was similar in appearance, and in response to culture conditions, to that reported by other investigators, including increased breakage in media supplemented with distamycin A. Sampling variation in the frequency of breakage over time may be considerable in some individuals. No pattern of anomalies was found to be associated with the fragile site. However, the reproductive history of the family we report (two livebirths with major congenital anomalies and one stillbirth) suggests caution in concluding fra(16)(q22) is not deleterious.
Mitral valve prolapse and aortic dilatation in the fragile X syndrome
Authors: Hagerman Randi J. , Synhorst David P. , Opitz John M.
Published: June 2005

Four patients with the fragile X syndrome including 3 males and one woman, were evaluated for cardiological abnormalities. One patient had an obvious murmur. All 4 were shown to have mitral valve prolapse by echocardiography. Two male patients also demonstrated mild dilatation of the ascending aorta. We recommend thorough cardiological evaluations of all fragile X patients.
Restudy of the original marker X family
Authors: Lubs Herbert A. , Watson Michael , Breg Roy , Lujan Enrique , Opitz John M.
Published: June 2005

Restudy of the original marker‐X family confirmed recent observations that this XLMR disorder is associated with large testes and slightly abnormal ears. However, other aspects of the phenotype were variable and a distinct facies was not evident. Significant differences in marker‐X frequency between two laboratories processing the same samples were observed. Possibly, the combination of more cells and a longer culture time in one laboratory led to a greater depletion of critical nutrients and a higher frequency of the marker‐X, but additional studies are needed. No evidence was found of a diminishing frequency of the marker‐X over a 15 year period.
Experience with prenatal fragile X detection
Authors: Jenkins Edmund C. , Brown W. Ted , Brooks Judith , Duncan Charlotte J. , Rudelli Raul D. , Wisniewski Henry M. , Opitz John M.
Published: June 2005

We have attempted the prenatal detection of the fra(X) 9 times. Three fra(X) positive fetuses have been diagnosed: 2 males and one female. The diagnosis on the 2 males has been confirmed. The testes of the 2 fra(X) positive fetuses appeared large for gestational age. However, results of anthropometric, bone age, anatomical and neurohistological studies were normal. Normal outcome was confirmed after birth in 2 males and one female on the basis of whole blood fra(X) studies. A presumptively positive female and a presumptively negative males remain unborn. Further presumptively negative males remain unborn. Further experience is needed to establish the reliability of the prenatal detection of fra(X)(q27).
The fragile‐X syndrome, IV. Progress towards the identification of linked restriction fragment length variants (RFLVs)
Authors: Holden Jeanette J. A. , Wang Hungshu , White Bradley N. , Opitz John M.
Published: June 2005

We present our strategy and progress towards the identification of rare restriction fragment length variants (RFLVs) segregating with the fragile‐X syndrome. DNA from a carrier mother and two retarded sons was digested with 7 restriction endonucleases and Southern blots were probed with cloned unique X‐chromosomal sequences. Two of 17 cloned segments tested revealed RFLVs between the X‐chromosomes of the carrier mother. One of them detected variants using Pvu II and Msp I. The Pvu II and Msp I alleles found on the X‐chromosome bearing the fragile‐X mutation were not found in 31 and 22 random X‐chromosomes, respectively. The other probe detected variants using Pvu II and Taq I. The Taq I allele present on the X‐chromosome with the fragile‐X mutation was found in 23 out of 25 random X‐chromosomes, while the Pvu II allele was not found in 21 random X‐chromosomes. One of these probes and two other cloned unique X‐chromosome sequences were localized distal to Xq26 by in situ hybridization to prometaphase chromosomes and by probing Southern blots containing DNA from a deleted X‐chromosome. These are being used for linkage analysis in an extended family.
Folate metabolism in humans
Authors: Erbe Richard W. , Wang Jin‐Chen C. , Opitz John M.
Published: June 2005

Several lines of evidence have linked flate metabolism to the expression of the fragile site at Xq27. Sutherland (1979) observed that expression of this marker depends on the composition of the culture medium and that deficiency of folic acid and thymidine promotes expression of the fragile site in lumphocytes, as does the addition of methotrexate. Several investigators (Glover, 1981; Tommerup et al, 1981) independently showed that expression of the fragile site can be elicited by adding 5‐fluorodexyuridine, an inhibitor of thymidylate synthase to culture medium containing folic acid but not thymidine. Indeed, Lejeune (1981) has claimed sucessful treatment of males with fragile X syndrome, the administration of folic acid and folinic acid (5‐formyltetrahydrofolate) leading to decreased expression of the Xq27 fragile site and greatly reduced aggressiveness. These and other studies have stimulated persons of diverse backgrounds to ocnfront complicated aspects of folate metabolism. The information that follows is intended to facilitate discusion and investigation in the context of the fragile X syndrome.

The history of folic acid can be said t date from the description by Channing in 1842 of severe, rapidly progressive and sometimes fatal anemia of pregnancy. In a series of studies begun in 1930, Lucy Wills observed that the diets of mothers of premature infants in India were usually markedly deficient in a vitamin that later proved ot be folic acid. Folic acid was first isolated and specifically maned in 1941 by investigators who prepared it from spinach leaves. It was first synthesized in 1946 and given the chemical designation pteroylglutamic acid. Syntheitic folic acid is now prepard in commercial quantities but is an unnatural substance. Biologically active folates are derivatives of tetrahydrofolate (THF) shown in Fig. 1. The has three major components, namely, the pteridine ring, the p‐aminobenzoate protion and an L‐glutamyl residue. The similarity of the sulfonamides ot the aminobenzoate protion of THF is the basis for the lethal effects sulfonamides have on microorganinsms, this treatment interfering with synthesis of folates. THF is the parent compound of all biologically active folates and is simply folic acid reduced on the pteridine ring at positons 5,6, 7 and 8 (Fig. 1). Two protions of the THF molecule are especially important to its functions. The nitrogen atoms at positions 5 or 10 or both carry the substituents that make up the one‐carbon pool. Of these compounds, 5‐methylTHF is the main serum and tissue form of folate, while, in most tissues, there are in addition lesser amounts of 10‐formylTHF and still smaller amounts of 5,10‐methyleneTHF, THF itself and other folate compounds. Very few of these folates are stable enough to be useful under clinical and cell folinic acid or leucovorin. This stable folate can be prepared in large quantities and can be given t patients orally or parenterally.
A new X‐linked syndrome comprising progressive basal ganglion dysfunction, mental and growth retardation, external ophthalmoplegia, postnatal microcephaly and deafness
Authors: Schimke R. Neil , Horton William A. , Collins Debra L. , Therou Leona , Opitz John M.
Published: June 2005

We report on 4 boys (3 in one family) who have a remarkably constant syndrome of childhood‐onset choreoathetosis with later spasticity, postnatal microcephaly, growth and mental retardation, apparent external opthalmoplegia and varying degrees of deafness. The pedigrees are consistent with X‐linked inheritance. The syndrome is compared and contrasted with others comprising basal ganglion dysfunction in childhood. It is concluded that clinically and genetically the condition is unique.
The Tel Hashomer camptodactyly syndrome in a consanguineous Brazilian family
Authors: Gollop T. R. , Colletto G. M. D. D. , Opitz John M.
Published: June 2005

We report on two Brazilian sibs whose parents are first cousins with clinical findings of the Tel Hashomer camptodactyly syndrome, namely, camptodactyly, muscle hypoplasia, skeletal abnormalities, and abnormal palmar creases. Both affected sibs have flat orbital roofs not described in previous cases and a high number of dermatoglyphic arches. The patient's father had camptodactyly of the fifth fingers, possibly a heterozygote manifestation.