bluuebunny/crossref_metadata_2025 huggingface dataset:
Implications of malformations not due to amniotic bands in the amniotic band sequence
Authors: Hunter Alasdair G. W. , Carpenter Blair F. , Opitz John M. , Reynolds James F.
Published: June 2005

It is widely accepted that the primary event in the amniotic band sequence (ABS) is early rupture of the amnion, and that the development of the fetus is then disrupted by entanglement and abrasion. The mechanism of the initial rupture is unknown. An argument raised in favor of this theory has been the apparent absence of non‐band‐derived malformations in the ABS. Here we report on four infants with ABS and additional malformations that are not readily explainable on the basis of band disruptions. These infants, together with some additional observations in the literature, and a growing number of reports of familial ABS, raise the question as to whether the formation of bands and other „non‐disruption”︁ abnormalities may have a common primary etiology in some cases. The primary mechanism could operate through disturbing the vascular system, and the factors involved might be both extrinsic or intrinsic, and some instances might date to an abnormality of the germ disk.
Non‐reciprocal translocation (5;15), isodicentric (15) and Prader‐Willi syndrome
Authors: Murdock Rosamond L. , Wurster‐Hill Doris H. , Opitz John M. , Reynolds James F.
Published: June 2005

A non‐reciprocal translocation (5;15) and an isodicentric (15) resulting in trisomy 15pter→15ql?3 and monosomy 5qter [46,XY,−5,−15,+der(5)t(5;l5)(5pter→5q35::15q13→15qter),+idic(15)(pter→ql?3::ql?3→ pter)] was found in a 28‐year‐old profoundly retarded male resident of a state institution. Early developmental history and childhood and adult physical findings resembled those of Prader‐Willi syndrome (PWS) patients. The parents' unbanded chromosomes were normal. Blood groups of parents and propositus were uninformative with regard to identifying gene deletions or duplications.
Isolated and syndromic cryptophthalmos
Authors: Thomas I. T. , Frias J. L. , Felix V. , de Leon L. Sanchez , Hernandez R. A. , Jones M. C. , Reynolds James F.
Published: June 2005

The association between cryptophthalmos and multiple congenital malformations has been well documented over the last century. Numerous authors have described case as the cryptophthalmos syndrome, but recently reports of cases without cryptophthalmos have led several authors to use the eponymic designation Fraser syndrome.

We have seen seven cases of cryptophthalmos syndrome, including three sib pairs. All presented with cryptophthalmos and bilateral renal agenesis in addition to other characteristic associated malformations. A literature review showed 124 cases in which 27 demonstrated isolated cryptophthalmos, while 97 showed a pattern of multiple congenital malformations. We selected four major and eight minor criteria which enabled us to classify 86 of those cases as having cryptophthalmos syndrome with 11 remaining unclassified.

Cryptophthalmos demonstrates equal sex distribution, occurrence in sibs, consanguinity in families with more than one affected child, and lack of vertical transmission—strongly suggesting autosomal recessive inheritance. Isolated cryptophthalmos or cryptophthalmos sequence was sporadic in 16 cases and familial in 11. The familial cases occurred in three families and demonstrated vertical transmission.

The pathogenesis of this syndrome is unknown. There are similarities to animal models of maternal vitamin A deprivation and defects in programmed cell death. Cryptophthalmos syndrome should be considered in the differential diagnosis of cases with multiple congenital malformations, especially when they are associated with renal agenesis, even in the absence of cryptophthalmos.
Duchen: An interactive computer program for calculating heterozygosity (carrier) risks in X‐linked recessive lethal diseases, and its application in duchenne muscular dystrophy
Authors: Andrews David F. , Brasher Penelope M. A. , Manchester Kathryn E. , Percy Maire E. , Rusk Ann C. M. , Soltan Hubert C. , Trueman David W. , Reynolds James F.
Published: June 2005

The program DUCHEN calculates the probability that a woman is a carrier of an X‐linked, lethal recessive disease on the basis of information in the woman's family and any available biochemical data. It is easily used by persons without computer knowledge or experience. The present version can accommodate families consisting of up to 100 people in seven generations. Risks may be estimated on the basis of pedigree information only, or with the inclusion of one or more types of biochemical test results. Biochemical data are incorporated with pedigree information into final risks using the powerful statistical technique of logistic discrimination, a procedure particularly suited for the separation of non‐normal populations on the basis of overlapping quantitative characteristics. Mutation rates are specified separately for males and females. DUCHEN is available in FORTRAN 77, IBM BASIC, and Applesoft BASIC, and may be used on a variety of mainframe or microcomputers.

The model was used to calculate risks for 375 girls and women in 46 families with Duchenne muscular dystrophy (DMD); serum creatine kinase tests had been carried out on 167 of these subjects who were of reproductive age. Carrier probabilities equal to or lower than the population risk (0.0004) were obtained for 21% of the aunts and 43% of the cousins of affected boys from families with an isolated case of DMD and for 14% of the cousins of affected boys from families with a known DMD history. DUCHEN should assist counsellors in determining which members of large families should be further examined using either standard biochemical carrier detection methods or DNA marker studies. Moreover, if the results of the latter are not decisive, then carrier probabilities provided by DUCHEN may be combined with information from DNA marker studies to yield more precise final risks.
Perception of consanguineous marriages and their genetic effects among a sample of couples from beirut
Authors: Khlat Myriam , Halabi Suzan , Khudr Adele , Der Kaloustian Vazken M. , Opitz John M. , Reynolds James F.
Published: June 2005

We interviewed 100 women who had married a relative and 100 other women of the same age, religious affiliation, and socioeconomic status, but who were not related to their husbands. Both women were selected from a hospital setting in Beirut, and were questioned about their outlook on consanguineous marriages, their awareness of the genetic consequences of consanguinity, and their relationships with in‐laws. In general, the women in consanguineous marriages were more favorably inclined than the matched women to marriages between relatives; however, about half of each group would advise their son/daughter to marry his/her cousin. Awareness of the genetic consequences of consanguinity was wide‐spread among the respondents, although the women who had married a relative were reluctant to express it. These women also reported better relationships with in‐laws, which may be considered as a social benefit derived from consanguineous marriages. Based on the above findings, recommendations are made regarding the content of a public health educational program.
New evidence for genetic heterogeneity of the Freeman‐Sheldon syndrome
Authors: Sánchez José María , Kaminker Catalina Patricia , Opitz John M. , Reynolds James F.
Published: June 2005

We report on two sibs (a boy and a girl) with the Freeman‐Sheldon (FS) syndrome (also called cranio‐carpo‐tarsal “dysplasia” or whistling face syndrome), born to normal parents. This unusual finding may represent genetic heterogeneity, germinal mutation of an autosomal dominant gene, and an epistatic recessive gene that supressed the expression of the abnormal gene in the father, his parents being first cousins. The last 2 mechanisms seem less probable.
Couple agreement before and after genetic counseling
Authors: Sorenson James R. , Wertz Dorothy C. , Reynolds James F.
Published: June 2005

Before receiving genetic counseling, 699 couples completed questionnaires that were identical for both spouses. Of 385 couples where both spouses indicated a major reason for seeking counseling, 45% identified the same major reason while 55% identifed different reasons. In 74% of 542 fertile couples, both spouses had identical short‐term reproductive plans: 60% desired the same ideal number of children; and 44% perceived the same level of risk of having an affected child. Agreement on the seriousness of eleven potential problems occasioned by an affected child ranged from 55% to 67%.

Couples were asked to return questionnaires within 7 to 10 days after counseling. At this time 76% of spouses agreed about short‐term reproductive plans; 66% agreed about longer‐term reproductive plans; and 60% agreed about ideal number of children. There were statistically significant increases in agreement about risk interpretation and about six of eleven potential problems in raising an affected child. The data suggest that a substantial number of couples come to genetic counseling with varying concerns and reproductive plans. There is, in general, as much disagreement on these issues between spouses after as before counseling. Implications for counseling are discussed.
Actin and myosin multigene families. Their expression during the formation and maturation of striated muscle
Authors: Buckingham Margaret , Alonso Serge , Barton Paul , Cohen Arlette , Daubas Philippe , Garner Ian , Robert Benoît , Weydert André , Opitz John M. , Reynolds James F.
Published: June 2005

The initial formation of skeletal muscle fibers is accompanied by the expression of muscle‐type actin and myosin genes. During subsequent maturation of muscle fibers in vivo, developmental changes in the fetal/adult isoforms of these proteins occur. Skeletal muscle‐specific transcripts coding for different myosin heavy chains accumulate sequentially both in vivo and in vitro. A genetic analysis demonstrates that these genes are clustered, implicating cis‐acting regulatory factors. In contrast, actin and myosin light chain genes are dispersed in the mouse genome. These gene families show a different developmental “strategy”: Genes expressed in adult cardiac tissue are coexpressed with the corresponding skeletal muscle sequence during fetal development. This phenomenon also occurs in adult tissue. Under conditions of cardiac overload, adult rat hearts accumulate skeletal actin mRNA and cardiac actin transcripts. In some mouse lines, a mutant cardiac actin gene locus is present. The presence of a second active upstream promoter at this locus depresses transcription of the bona fide gene, resulting in low levels of mature cardiac actin mRNA. In this situation skeletal actin gene transcripts accumulate. Genes expressed in the same fetal or adult muscle phenotype are not linked, suggesting that their coexpression is regulated by transacting factors. The promoter regions of such genes in the mouse have no common characteristics of primary structure with the exception of an ElA‐type enhancer core sequence, which has a conserved 5′ flanking element, seen for actin and myosin light chain genes. Reintroduction of these promoter regions into muscle cells provides a functional test for such potential regulatory sequences.
Chromosome anomalies as predictors of recurrence risk for spontaneous abortion
Authors: Morton N. E. , Chiu D. , Holland C. , Jacobs P. A. , Pettay D.
Published: June 2005

Reproductive histories and chromosomes of spontaneous abortions were studied by segregation analysis in 1890 sibships ascertained through a cytogenetically studied abortion. Normal karyotypes are associated with recurrent abortion. Among abnormal karyotypes, trisomy has an elevated recurrence risk even after adjustment through a liability indicator for maternal age. Possible mechanisms and conflicting evidence in the literature on trisomy are discussed. None of these differences in recurrence risk is large enough to play a significant numerical role in genetic counseling.
Psychological aspects of genetic counseling: IV. The subjective assessment of probability
Authors: Kessler Seymour , Levine Eleanor K. , Opitz John M. , Reynolds James F.
Published: June 2005

Subjects asked to compare mathematically equal statements (or frames) of probability invariably perceived a difference in magnitude between percentages and equivalent proportions. Presented as unrelated to genetic risk, percentages tended to be chosen as having greater magnitude than their equivalent proportions. In justifying their choices subjects used a process of reasoning in which numbers were mentally compared, contrasted, or otherwise manipulated (numerical strategy). When framed as genetic risks, two types of reasoning were used to assess probabilities, the numerical strategy and one involving mental images of persons or parts of persons (person strategy). Subjects who used numerical reasoning tended to perceive percentages as having a greater risk magnitude than equivalent proportions whereas when person reasoning was used proportions with denominators of 10 or less tended to be perceived as having a greater risk magnitude than equivalent percentages. The implications of the findings for genetic counseling are discussed.
A specific syndrome due to deletion of the distal long arm of chromosome 1
Authors: Meinecke Peter , Vögtel Dagmar , Opitz John M. , Reynolds James F.
Published: June 2005

We have studied 2 patients with de novo deletion 1 (q42.3 → qter): a 5 1/2‐year‐old boy and an unrelated 1 9/12‐year‐old girl. The analysis of the phenotype which is now possible in a total of 23 cases shows that the deletion of the terminal 1q leads to a definable multiple congenital anomalies/mental retardation (MCA/MR) syndrome. The phe‐notype is so characteristic that, as a rule, the clinical data should suggest the correct cytogenetic diagnosis.
Occurrence of desmoids in patients with familial adenomatous polyposis of the colon
Authors: Klemmer Sarah , Pascoe Leigh , DeCosse J. , Opitz John M. , Reynolds James F.
Published: June 2005

Desmoid tumors occur at a much higher frequency in association with familial adenomatous polyposis than with any other disease. However, published estimates of risk have varied widely. In this study we have examined the occurrence of desmoids in a population of polyposis patients in order to determine an accurate estimate of the risk of desmoid disease. The crude frequency of desmoids in our population was about 6%, but the risk was dependent on the age and sex of the individuals at risk. The lifetime risk of incurring a desmoid was 8% for males and 13% for females. The distribution of occurrence of desmoid disease with regard to age was unimodal in each sex in contrast to the multimodal distribution observed for desmoids in nonpolyposis patients. Females were more likely to be affected than males and at an earlier age. We also detected heterogeneity of risk between families segregating for the polyposis gene, with the desmoid disease tending to cluster in some of those families. Consequently crude estimates of risk should be used with caution.
Rapid cell culture procedure for tissue samples
Authors: Gray Brian A. , Gollin Susanne M. , Opitz John M. , Reynolds James F.
Published: June 2005

Cell culture is an integral part of genetic studies, including cytogenetic, metabolic, and DNA analyses. Standard culture procedures used today involve plating minced tissue explants in dishes and waiting 3 to 4 weeks for adequate growth. We describe a method that utilizes collagenase digestion of tissue biopsies, enabling cell harvest as soon as 3 days after culture initiation; this has been used successfully in our laboratory for cytogenetic and metabolic studies. Culture duration can be controlled by the cell plating density. Although collagenase digestion of tissues is commonly used in cytogenetics laboratories for tumor or chorionic villous dissociation, we have found that few labs have considered using this rapid and efficient procedure for routine tissue samples.
Clinical, cytogenetic, and pedigree findings in 18 cases of Aicardi syndrome
Authors: Donnenfeld Alan E. , Packer Roger J. , Zackai Elaine H. , Chee Claire M. , Sellinger Bea , Emanuel Beverly S.
Published: June 2005

Eighteen girls with Aicardi syndrome were identified through a survey of neurologists, geneticists, and ophthalmologists. All had infantile seizures, developmental delay, agenesis of the corpus callosum (complete: 72%, partial: 28%), and characteristic chorioretinal lacunar lesions. Costovertebral defects including hemivertebrae, scoliosis, and absent or malformed ribs were present in 39%, cortical heterotopias were present in 50%, and microphthalmia was identified in a third. Cytogenetic investigation was carried out in all families. An unbalanced X;3 translocation, 46,X,der(X)t(X;3) (p22.3;p23)mat, was discovered in a girl with chorioretinal lacunar lesions characteristic of Aicardi syndrome, developmental delay, and infantile seizures. However, this child had a normal appearing corpus callosum on CT and magnetic resonance imaging scans and therefore did not meet the criteria for inclusion in the study. Chromosomes of all other patients and parents were normal. Findings at birth, age of seizure onset, treatment, and prognosis are discussed. The pedigree data from these 18 families demonstrated an unaffected male:female sib ratio of 1:1.7 and a 14% spontaneous abortion rate. The findings of this study support the contention that Aicardi syndrome is an X‐linked dominant disorder with early embryonic lethality in hemizygous males and that all cases represent new mutations.
Osteoclast biology: Lessons from mammalian mutations
Authors: Marks Sandy C.
Published: June 2005

Major contributions to and confirmations of osteoclast biology have been made by experimental investigations of the osteopetrotic mutations in mammals. Congenital osteopetrosis is a bone disease characterized by a generalized increase in skeletal mass due to decreased osteoclast function. Abnormalities of skeletal growth and the failures of marrow cavity development and tooth eruption are secondary to reduced bone resorption of heterogeneous cause. Elucidation of pathogenetic pathways and unraveling of the cell biology of the osteoclast have proceeded hand‐in‐hand. This is illustrated by the variable differentiation and activation of osteoclasts among mutations and by demonstrations that the disease in certain animals and children can be cured by providing competent stem cells for osteoclasts via bone marrow transplantation. Congenital absence of carbonic anhydrase II (CA II) in children results in a syndrome that included osteopetrosis because osteoclasts are unable to function in the absence of CA II. The resistance of all mutations to the hypercalcemic effects of parathyroid hormone and recent reports of elevated blood levels of 1,25 dihydroxyvitamin D have broadened the scope of pathogenetic possibilities for osteopetrosis and regulatory possibilities for osteoclasts. Immunological effects including reductions in natural killer cell activity, superoxide and interleukin‐2 production make osteopetrotic mutants potential models for studying the role of the immune system in osteoclast biology. Furthermore, coexistence of osteopetrosis with rickets and osteoblast abnormalities and the failure of cell transplants to cure the disease in some mutations illustrate the utility of the osteopetroses for exploring the role of matrix as mentor in osteoclast biology. Thus, understanding congenital osteopetrosis and osteoclast biology are likely to continue together.
Structure of the elastin gene and alternative splicing of elastin mRNA: Implications for human disease
Authors: Indik Zena , Yeh Helena , Ornstein‐Goldstein Norma , Kucich Umberto , Abrams William , Rosenbloom Joan C. , Rosenbloom Joel
Published: June 2005

The protein elastin is largely responsible for the elastic properties of vertebrate lungs, large blood vessels, and skin. The structure of the human, bovine, and chick elastin gene and protein monomer, tropoelastin, has recently been elucidated by using techniques of molecular biology. Extensive homology of amino acid sequence exists among the mammalian species and there is in addition strong conservation of nucleotide sequences in the 3′ untranslated region of the gene. The translated exons are small and embedded in large expanses of introns. Sequences coding for the hydrophobic regions, responsible for the elastic properties of the molecule, and the alaninelysine rich regions, responsible for crosslink formation between molecules, reside in separate exons and alternate for the most part in the elastin gene. S1 analyses and sequence analysis of cDNA and genomic clones have indicated that there is substantial alternative splicing of the primary elastin transcript. Variations in the structure of mRNAs resulting from alternative splicing could explain the existence of the multiple forms of tropoelastin observed electrophoretically in several species. Different kinds of splicing patterns could occur in human populations and may contribute to aging and pathological situations in the cardiovascular and pulmonary systems.
Tissue and cell studies of the growth plate in the chondrodysplasias
Authors: Horton William A. , Campbell Diana , Machado Mirta A. , Aulthouse Amy L. , Ahmed Saira , Ellard Jeffrey T.
Published: June 2005

As the morphologic expression of the chondrocytic differentiation pathway responsible for bone development and growth, the growth plate has been investigated extensively in the chondrodysplasias. Unique morphologic abnormalities identified in many disorders have provided insight into pathogenetic mechanisms and have been useful diagnostically and nosologically. Biochemical studies have detected evidence of type II collagen defects in patients having disorders in the achondrogenesis type II‐spondyloepiphyseal dysplasias (SED) congenita family of chondrodysplasias. Most promising may be the cell culture systems now being developed for human chondrocytes. Preliminary results suggest that they will allow the cellular and molecular biology of the dysplastic growth plate to be directly analyzed.
Pleiotropy revisited: Molecular explanations of a classic concept
Authors: Pyeritz Reed E.
Published: June 2005

As commonly used, pleiotropy refers to multiple effects on phenotype of a single mutant gene. The importance of this concept to medical genetics has waxed and waned since its formulation soon after the rediscovery of Mendel's laws. Initially, the view that all aspects of a phenotype, and hence all manifestations of a mendelian syndrome, derive from a single function (or dysfunction) of a mutant allele gained ascendancy. Support for the importance of pleiotropy gradually diminished, and reached a low point in the 1940s with the one gene‐one enzyme hypothesis. Studies of mammals and humans with heritable disorders of connective tissue sustained the notion that “genuine” pleiotropy probably did not exist. However, the demise of the relevance of pleiotropy was premature. Detailed understanding of gene organization, expression, and mutation indicates several mechanisms, such as multifunctional proteins, alternative splicing of messenger RNA, and overlapping coding sequences, through which genuine pleiotropy likely occurs in normal development and function, in mendelian syndromes, and in conditions due to somatic mutation. Furthermore, a broad definition of pleiotropy is warranted to subsume syndromes caused by abnormal function of contiguous genes, such as through large deletions, mutation of regulatory elements that coordinate expression, or less clearly understood “position effects.” Thus, the use of pleiotropy in the context of aneuploidy syndromes is not inappropriate.
Characterization of the calcitonin/CGRP gene in Williams syndrome
Authors: Russo Andrew F. , Chamany Katayoun , Klemish Steven W. , Hall Todd M. , Murray Jeffrey C.
Published: June 2005

We have investigated the possibility of mutations in the calcitonin/calcitonin gene related peptide (CGRP) gene in children with Williams syndrome. Involvement of the calcitonin/CGRP gene in Williams syndrome is postulated on the basis that Williams syndrome children often have infantile hypercalcemia and deficient expression of calcitonin, a hormone that lowers serum calcium levels. To test the hypothesis that mutations in the calcitonin/CGRP gene might be responsible for the reduced calcitonin levels, we examined the calcitonin/CGRP gene structure in Williams syndrome children. Analysis of white blood cell DNA by Southern blot hybridizations in 5 individuals did not show any detectable large deletions or rearrangements in the calcitonin/CGRP gene locus. The possibility of small deletions or point mutations within the exon encoding the mature calcitonin hormone is unlikely based on ribonuclease protection assays with patient DNA amplified by the polymerase chain reaction (PCR) technique. These findings suggest that the calcitonin deficiency might be due either to mutations elsewhere in the gene or to defects in the cellular machinery needed for calcitonin synthesis and/or secretion.
Understanding the decision to take the predictive test for Huntington disease
Authors: Meissen Gregory J. , Mastromauro Carol A. , Kiely Dan K. , McNamara Danielle S. , Myers Richard H.
Published: June 2005

The predictive test for Huntington disease (HD) has allowed those at risk to determine gene status prior to symptoms. The purpose of this research was to understand the motivation and the anticipated reactions of those requesting the test. Forty persons at 50% risk for HD and 31 companions participated in a structured personal interview as part of the predictive test protocol. Reasons for taking the test centered on the reduction of anxiety and uncertainty associated with being at risk and enhanced planning and decision making. Participants also believed that taking the test would produce more positive than negative outcomes. With a favorable result, most anticipated a reduction of anxiety, a more normal future, and relief knowing their children would be at a very low risk. Most also cited benefits as more likely than consequences with an unfavorable result. Making the most of life, easier planning, and reduced uncertainty were rated as more likely than any of the adverse impacts, including short‐term depression and becoming frightened. Almost all participants (95%) said they would rather learn that they have the HD gene than remain at 50% risk. The uncertainty, anxiety, and chronic stress associated with being at risk appears to underlie the motivation of many seeking the predictive test for HD.
Ectrodactyly of hands and feet in a child with a complex translocation including 7q21.2
Authors: Sharland Michael , Patton Michael A. , Hill Lucy
Published: June 2005

A three‐way translocation involving a break point of 7q21.2 was found in a boy with tetramelic ectrodactyly.
Molecular analysis of Gaucher disease in a Vietnamese‐Czechoslovak patient with high residual glucocerebrosidase activity
Authors: Choy Francis Y. M. , Woo Mary , Der Kaloustian Vazken M.
Published: June 2005

A Vietnamese‐Czechoslovak type 1 Gaucher disease patient with mild hematological complications was found to have approximately 20% of the normal level of fibroblast glucocerebrosidase activity. Using primers that recognize exon 9 sequences of the glucocerebrosidase structural gene absent in the pseudogene, genomic DNA sequences flanking exons 9 and 10 of the glucocerebrosidase structural gene were amplified by the polymerase chain reaction. Allele‐specific oligonucleotide hybridization to amplified genomic DNA sequence of exons 9 and 10 showed an A→G transition in exon 9 that resulted in the 370Ser→370 Asp substitution in one of the alleles. In the other allele, a T→C transition in exon 10 resulted in the 444Leu→444Pro substitution, creating a NciI cleavage site. The heterozygote status of the patient's parents was confirmed biochemically by the detection of intermediate levels (42–55% of normal) of fibroblast glucocerebrosidase activity. Allele‐specific oligonucleotide hybridization to amplified parental genomic DNA showed that the exon 9 mutation was present in the Czechoslovak father, whereas the exon 10 mutation was inherited from the patient's Vietnamese mother. This is the first report of the exon 10 mutation in a person of Vietnamese origin.
Genetic epidemiology of hereditary motor sensory neuropathies (type I)
Authors: Mostacciuolo M. L. , Micaglio G. , Fardin P. , Danieli G. A.
Published: June 2005

Patients affected with hereditary motor sensory neuropathy (HMNS) type I were traced through hospital records. Each case was re‐examined, a family history was drawn, and EMG examination was performed in those members of the family who could have inherited the trait. In the prevalence year 1987, in a population of 1,067,130 inhabitants of 2 contiguous provinces of northeast Italy, 100 living cases were recorded in 30 families, giving a minimal prevalence rate estimate of 9.37/100,000. HMSNI is inherited as an autosomal dominant trait, when clinical evaluation includes EMG. No difference may be established clinically between the 2 subtypes (Ia, linked to chromosome 1 and Ib, linked to chromosome 17). Sporadic cases are very rare and the mutation rate, including both the subtypes, is estimated between 3 and 6×10−6.
Renal tubular dysgenesis and very large cranial fontanels in a family with acrocephalosyndactyly S. C. type
Authors: Russo Rosa , D'Armiento Maria , Vecchione Raffaella
Published: June 2005

We describe the first case of renal tubular dysgenesis in a newborn female who survived 15 days. The immunohistochemical and lectin binding studies confirmed the lack of proximal tubule differentiation. Electron microscopy showed undifferentiated tubular epithelium. Widely patent cranial fontanels were present in the proposita. The father and sister showed acrocephalosyndactyly Saethre‐Chotzen type. The parents were not related and there was no familial history of renal pathology.
Short stature, mental retardation, eye anomalies, and cleft lip/palate
Authors: Richieri‐Costa A. , Guion‐Almeida M. L.
Published: June 2005

The syndrome: We describe 3 Brazilian brothers presenting a cluster of signs strongly suggesting a “new” MCA/MR syndrome. The main clinical signs include short stature, microbrachycephaly, mental retardation, palpebral ptosis, coloboma of iris and retina, nystagmus, strabismus, and cleft lip/palate. This is either an autosomal or X‐linked recessive trait.
Amplification of ten deletion‐rich exons of the dystrophin gene by polymerase chain reaction shows deletions in 36 of 90 Japanese families with Duchenne muscular dystrophy
Authors: Kitoh Yoshihiko , Matsuo Masafumi , Nishio Hisahide , Takumi Toru , Nakajima Toshihiro , Masumura Takehiro , Koga Junichi , Nakamura Hajime
Published: June 2005

We analyzed DNA samples taken from 95 Duchenne muscular dystrophy (DMD) patients belonging to 90 different families in Japan using the polymerase chain reaction. Ten different regions at the 5′ end or in the central region of the dystrophin cDNA gene that were previously shown to be prone to deletion were selected for amplification and analysis. Patients in 36 of the 90 families (40%) had deletions in at least one of these segments of the gene. Identical deletions were detected in the dystrophin gene of patients from the same family. The deletions were heterogeneous in size and location. One patient had deletions in 7 of the 10 amplified regions, while 19 patients from 18 families had a deletion in only one of the regions studied. Deletions at the 5′ end were generally larger and more heterogeneous than those in the central region of the gene. One third of deletions had their proximal end breakpoints between exons 44 and 45. This region seems to be particularly vulnerable to gene breakage in DMD patients.
Predictive testing for Huntington disease in Canada: Adverse effects and unexpected results in those receiving a decreased risk
Authors: Huggins Marlene , Bloch Maurice , Wiggins Sandi , Adam Shelin , Suchowersky Oksana , Trew Michael , Klimek Marylou , Greenberg Cheryl R. , Eleff Michael , Thompson Louise P. , Knight Julie , MacLeod Patrick , Girard Kathleen , Theilmann Jane , Hedrick Amy , Hayden Michael R.
Published: June 2005

By January 1, 1991 a total of 388 persons had enrolled in the Canadian collaborative study of predictive testing for Huntington disease (HD). Of these participants, 105 persons have been given a decreased risk result. Contrary to expectations, approximately 10% of persons with a decreased risk result have had psychological difficulties coping with their new status. Here, we describe the individual responses of 6 such persons and experiential themes emerging after following these persons for up to 2 years. Individuals who are more likely to suffer an adverse reaction to a decreased risk result include those persons who have made irreversible decisions based on the belief they would develop HD or those who had unrealistic overoptimistic expectations of the positive effects of a decreased risk result. In contrast to those receiving an increased risk result, the most vulnerable time for persons receiving a decreased risk result is between 2 and 12 months after learning the outcome. The need for assessment and counselling of participants in predictive testing programs, even when there is a decreased risk result, is emphasized.
Cutaneous scar at anterior hair line in mother and child with associated frontal bone defect in child
Authors: Stratis John P. , Ramer Jeanette C. , Manders Ernest K. , Lehman Ralph A. , Ladda Roger L.
Published: June 2005

A large frontal bone defect underlying a “V” shaped scar was noted in a newborn male whose mother had an identical “V” shaped scar at the same location in the anterior hairline. Both had hypertelorism and short palpebral fissures. The mother had no radio‐graphic evidence of skull defect and neither mother nor child had other cutaneous or skeletal anomalies. Cranioplasty was performed on the child using the remaining frontal bones with an excellent cosmetic result. Biopsy performed at operation documented scar tissue extending through the dermis and underlain by thickened dura. Mother and child appear to have a variant form of aplasia cutis congenita, an autosomal dominant trait with wide variation in expression. © 1992 Wiley‐Liss, Inc.
Deletions and microdeletions of 22q11.2 in velo‐cardio‐facial syndrome
Authors: Driscoll Deborah A. , Spinner Nancy B. , Budarf Marcia L. , McDonald‐McGinn Donna M. , Zackai Elaine H. , Goldberg Rosalie B. , Shprintzen Robert J. , Saal Howard M. , Zonana Jonathan , Jones Marilyn C. , Mascarello James T. , Emanuel Beverly S.
Published: June 2005

Velo‐cardio‐facial syndrome (VCFS), an autosomal dominant disorder, is characterized by cleft palate, cardiac defects, learning disabilities and a typical facial appearance. Less frequently, VCFS patients have manifestations of the DiGeorge complex (DGC) including hypocalcemia, hypoplastic or absent lymphoid tissue and T‐cell deficiency suggesting that these 2 conditions share a common pathogenesis. Here, we report the results of cytogenetic and molecular studies of 15 VCFS patients. High ‐ resolution banding techniques detected an interstitial deletion of 22q11.21‐q11.23 in 3 patients. The remaining 12 patients had apparently normal chromosomes. Molecular analysis with probes from the DiGeorge Chromosome Region (DGCR) within 22q11 detected DNA deletions in 14 of 15 patients. In 2 families, deletions were detected in the affected parent as well as the propositus suggesting that the autosomal dominant transmission of VCFS is due to segregation of a deletion. Deletions of the same loci previously shown to be deleted in patients with DGC explains the overlapping phenotype of VCFS and the DGC and supports the hypothesis that the cause of these two disorders is the same. © 1992 Wiley‐Liss, Inc.
Postaxial acrofacial dysostosis: Report on two patients
Authors: Pereira Sonia C. S. , Rocha Christiane M. G. , Guion‐Almeida M. L. , Richieri‐Costa A.
Published: June 2005

We report on 2 patients with the postaxial acrofacial dysostosis (AFD) syndrome. One patient was an isolated case; the other had an equally affected brother previously described [Richieri‐Costa and Guion‐Almeida, 1989]. Recurrence in sibs suggests autosomal recessive inheritance. © Wiley‐Liss, Inc.
New autosomal recessive syndrome of mental retardation, epilepsy, short stature, and skeletal dysplasia
Authors: Gurrieri F. , Sammito V. , Bellussi A. , Neri G.
Published: June 2005

We describe 4 sibs, 2 males and 2 females, affected with a new autosomal recessive MCA/MR syndrome of short stature, cerebral atrophy, epilepsy, skeletal abnormalities, and moderate to severe mental retardation. © Wiley‐Liss, Inc.
Acrometageria: A spectrum of “premature aging” syndromes
Authors: Greally J. M. , Boone L. Y. , Lenkey S. G. , Wenger S. L. , Steele M. W.
Published: June 2005

A child with manifestations of acrogeria and metageria, two “premature aging” syndromes, is presented. Because of his indistinct phenotype and because the question has been previously raised as to whether these conditions are separate, we propose the designation of acrometageria to describe this phenotypic continuum. As there is much in common clinically between acrometageria and the syndrome of type III procollagen deficiency (Ehlers‐Danlos type IV), it might be presumed that a similar pathogenesis for acrometageria exists. This possibility has been tested previously, without demonstrating specific quantitative or qualitative deficits, but with some indirect evidence that collagen metabolism is deranged in these patients. One such crude indicator is the elevation of urinary hyaluronic acid levels, demonstrated in our patient and also observed in the phenotypically distinct Werner and Hutchinson‐Gilford premature aging syndromes. On one hand, it could be argued that this supports the concept that premature aging syndromes exist as a biological continuum. On the other hand, it is equally valid to argue that syndromes of premature aging are so described merely because they include recognizable changes of normal aging and that the demonstration of an underlying mutation in a collagen gene, for example, invalidates their study as models of accelerated normal aging. © Wiley‐Liss, Inc.
Prognosis of prenatally diagnosed children with sex chromosome aneuploidy
Authors: Robinson Arthur , Bender Bruce G. , Linden Mary G.
Published: June 2005

Sex chromosome aneuploidy (SCA) occurs in about 1/250 amniocenteses, and the significance of the long‐term prognosis of fetuses with SCA is of concern to prospective parents and health care providers. Longitudinal studies in an unselected group of newborn infants with SCA diagnosed postnatally have refuted allegations of mental retardation but have documented an increased risk for developmental problems. Of the 530 phone consultations with parents faced with a prenatal diagnosis of SCA, 68% continued the pregnancy. Twenty of the oldest subsequently born children (now 7–14 years old) were available for follow‐up. In this small sample and age group, the propositi are progressing developmentally at a rate comparable to their sibs and are doing better at school and in peer relations than the SCA group diagnosed postnatally. Only 2 have documented IQs as low as 90. The documented IQs of the remainder, none of whom are sex chromosome mosaics, are all over 110. The parent population in this prenatally diagnosed group is unique and different from that of the postnatally diagnosed group in that over 85% of them are college graduates, often professionals, and upper socioeconomic individuals. The developmental competence of this SCA sample may be attributable to the supportive environment provided by these families, all of whom made a conscious decision to continue the pregnancy. © Wiley‐Liss, Inc.
Commingling and complex segregation analysis of fasting plasma glucose in the lipid research clinics family study
Authors: Rice Treva , Laskarzewski Peter M. , Rao D. C.
Published: June 2005

Commingling and segregation patterns of fasting plasma glucose (GL) were examined in family data from 5 clinics (Cincinnati, Stanford, Iowa, Minnesota, and Oklahoma) of the Lipid Research Clinics (LRC) family study. In addition to the primary question of whether there was a major gene for GL, a secondary purpose was to investigate the possibility of genetic heterogeneity among the 5 clinics. No statistical support was found for heterogeneity among clinics, either in the commingling of distributions or in the segregation patterns. For the combined clinics sample, both a major effect and a multifactorial component were significant. However, the major effect (accounting for 73% of the variance) was not found to be consistent with a major gene, as the hypothesis of Mendelian transmission was rejected. The most parsimonious model involved equal transmission probabilities, which suggests that the major effect is not transmitted from parents to offspring. Possible sources of this major non‐Mendelian effect were explored. The multifactorial component accounted for 10% of the variance in GL levels, and no generational differences were noted. Although our study was unable to provide evidence in favor of a major gene effect, it should be noted that a major gene cannot be firmly refuted. For example, a variety of interactions, such as genotype‐dependent age effects, could have masked the transmission probabilities.
Patterns of acrorenal malformation associations
Authors: Evans Jane A. , Vitez Marta , Czeizel Andrew
Published: June 2005

Limb and urinary tract defects have frequently been reported to occur together as components of a single acrorenal field defect or in many multiple malformation syndromes. However, the concordance of such anomalies has rarely been studied on a population basis or the relationships between specific limb and renal defects defined. This paper documents the patterns of acrorenal associations seen in over 1,500,000 infants born in Hungary in 1975–1984. In all, 1 in 1,800 infants had a limb deficiency and 9% of these (75 cases) had a urinary tract anomaly. Urinary tract anomalies were most commonly seen with radial ray defects, micromelia and amelia. The commonest recognized patterns were VACTERL association and the cloacal exstrophy and caudal regression sequences. Chromosomal and single gene defects also occurred.

Numerical taxonomic techniques delineated six main clusters of patients. Important groupings included micromelia with renal agenesis, split hand/foot with hydronephrosis, and radial ray anomalies with VACTERL defects. The radial ray groups differed in the nature of the VACTERL anomalies seen and with respect to laterality, symmetry, and non‐VACTERL anomalies. There was a strong association of bilateral limb defects with bilateral renal anomalies and unilateral with unilateral. Ipsilateral defects tended to occur in typical VACTERL cases, while contralateral defects tended to occur with additional non VACTERL midline anomalies.

Although renal and limb anomalies are associated, in almost all cases malformations in other systems are also present. The precise nature of the malformation patterns seen appear to reflect differences in the nature and magnitude of the underlying dysmorphogenetic processes as well as the timing of their effects. © Wiley‐Liss, Inc.
Trisomy 22 with congenital diaphragmatic hernia and absence of corpus callosum in a liveborn premature infant
Authors: Kim Eun H. , Cohen Ronald S. , Ramachandran Pramela , Mineta Albert K. , Babu V. Ramesh
Published: June 2005

We report on a liveborn premature male with trisomy 22 who had multiple congenital anomalies, including congenital diaphragmatic hernia and absence of corpus callosum. He died of pulmonary hypoplasia associated with diaphragmatic hernia within 12 hours of age. Chromosome analysis by multiple banding techniques based on lymphocyte culture confirmed that he had trisomy 22. This may be the first report of congenital diaphragmatic hernia and isolated absence of corpus callosum associated with trisomy 22. © Wiley‐Liss, Inc.
Molecular detection of a 4p deletion using PCR‐based polymorphisms: A technique for the rapid detection of the Wolf–Hirschhorn syndrome
Authors: Altherr Michael R. , Gusella James F. , Wasmuth John J. , Kummer Mark A. , McKercher Scott W. , Johnson Virginia P.
Published: June 2005

Wolf–Hirschhorn syndrome (WHS) results from a deletion of part of chromosome 4p. The region of 4p consistently deleted in WHS is near the tip of 4p. Two loci in this region D4S95 and D4S125 are associated with highly informative VNTR polymorphisms and were recently converted to allow PCR‐based screening. PCR analysis was used successfully to identify a small de novo deletion of 4p in a patient suspected of having WHS. This procedure allows a rapid and accurate confirmation of 4p deletions in cases where cytogenetics alone cannot provide a clear answer. © Wiley‐Liss, Inc.
Saethre–Chotzen syndrome with trigonocephaly
Authors: Cristofori Guido , Filippi Giorgio
Published: June 2005

We report on a 20‐month‐old boy with skull malformations and motor delays. A diagnosis of Saethre–Chotzen syndrome was made in view of the clinical and neuroradiological signs. Other unusual findings were trigonocephaly and occipital dysplasia with medial schisis at the foramen occipitalis. The mother showed a mild expression of the syndrome. © 1992 Wiley‐Liss, Inc.
X‐linked recessive inheritance of dysgenesis of corpus callosum in a chinese family
Authors: Kang Wun‐Ming , Huang Chao‐Ching , Lin Shio‐Jean
Published: June 2005

This report describes a new syndrome of dysgenesis of corpus callosum with other anomalies, presenting as microcephaly, mental retardation, spasticity, and unusual facial appearance in 2 Chinese brothers and their maternal cousins. To date, there has not been any case reported in the Chinese population of this syndrome. All 4 patients in this report present with the same unusual face. Hydrocephalus and/or interhemispheric cyst were found among them. This syndrome is transmitted as an X‐linked trait. The nosology is reviewed and discussed. © 1992 Wiley‐Liss, Inc.
Case reports of successful pregnancy in women with maple syrup urine disease and propionic acidemia
Authors: Van Calcar Sandra C. , Harding Cary O. , Davidson Susan R. , Barness Lewis A. , Wolff Jon A.
Published: June 2005

We report on 2 women with organic acidemias, one with classical maple syrup urine disease and another with mild propionic acidemia in which protein restricted diets and carnitine supplementation were successfully employed to manage pregnancies. Healthy infants were delivered without maternal metabolic decompensation. © 1992 Wiley‐Liss, Inc.
Cardio‐Facio‐Cutaneous syndrome: Three additional cases and review of the literature
Authors: Somer Mirja , Peippo Maarit , Aalto‐Korte Kristiina , Ritvanen Annukka , Niemi Kirsti Maria
Published: June 2005

We report on 3 patients with the cardio‐faciocutaneous (CFC) syndrome. Each of them was a sporadic case in the family. The severity of the psychomotor retardation varied from mild to severe. Skin manifestations were often minimal, but each patient had abnormally curly and brittle hair. A skin biopsy from one of the patients showed vellus hair cysts filled with keratin, and the hair follicles were surrounded by unusually thick fibrotic sheaths. © 1992 Wiley‐Liss, Inc.