bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of phenotypic and genetic heterogeneity in cystic fibrosis: Variability in sweat electrolyte levels contributes to heterogeneity and is increased with the XV‐2c/KM19 B haplotype
Authors: Witt Michal , Erickson Robert P. , Ober Carole , Howatt William F. , Farber Rosann
Published: June 2005

We have reinvestigated a classification of clinical heterogeneity among cystic fibrosis (CF) patients that we previously reported and investigated the possible relationship of the identified CF subgroups to haplotypes around the CF gene and to HLA‐DR haplotypes. Age‐corrected values for sweat electrolytes, rate of progression of lung disease as assessed by Brasfield chest x‐ray scores, and severity of pancreatic insufficiency as assessed by daily supplemented enzyme dosage were obtained for 55, 59, and 59 patients, respectively. XV‐2c and KM19 RFLPs were determined by hybridization to TaqI and PstI digests of human genomic DNA, respectively, and analysis of mutations by PCR amplification followed by allele‐specific oligo‐deoxy‐nucleotide hybridization was performed for 29 patients. HLA‐DR restriction fragment length polymorphisms (RFLPs) were determined by hybridization of cDNA β1 and genomic DQα probes to TaqI digests of human genomic DNA. The results show that the previous subdivision on the basis of age‐corrected levels of sweat electrolytes, as well as measures of severity of lung disease and pancreatic disease, is valid. In addition, the C and D haplotypes are associated with lower age‐corrected sweat sodium level. No significant relationship between CF haplotypes and the other two disease variables or between HLA‐DR haplotypes and any of the clinical variables was found.
Cardio‐Facio‐cutaneous (CFC) syndrome: Report of two patients without hyperkeratotic skin lesions
Authors: Matsuda Yukihisa , Murano Ichiro , Kondoh Osamu , Matsuo Kiyosato , Kajii Tadashi
Published: June 2005

We report on two boys with the cardio‐facio‐cutaneous (CFC) syndrome, but without hyperkeratotic skin involvement. They showed most of the manifestations of the CFC syndrome: growth and developmental retardation, relative macrocephaly, distinct facial appearance, sparse hair, and heart defects. Their skin was not hyperkeratotic, but patient 1 had mild atopic dermatitis and keloid‐like depigmented spots.
Estimating genetic influences on the age‐at‐menarche: A survival analysis approach
Authors: Meyer Joanne M. , Eaves Lindon J. , Heath Andrew C. , Martin Nicholas G.
Published: June 2005

A survival analysis regression model is described for analyzing twin data on the age‐at‐menarche. The model includes latent genetic and environmental covariates and allows one to test hypotheses regarding the nature of familial aggregation for age‐at‐onset. Additionally, the model accommodates a variety of baseline survival distributions and therefore may be used to test different developmental hypotheses. Model‐fitting results indicate that a survival model with a baseline gamma distribution gives an adequate fit to recalled age‐at‐menarche of 1,888 pairs of Australian female monozygotic and dizygotic twins. Further, results show that additive genetic and dominance genetic effects contribute to shared variation in age‐at‐menarche. If there are common environmental influences on the timing of menarche, they are completely obscured by nonadditivity in genetic factors, and information from other relationships would be required to detect their effect.
Presymptomatic, prenatal, and exclusion testing for Huntington disease using seven closely linked DNA markers
Authors: Skraastad Mette I. , Verwest Aart , Bakker Egbert , Vegter‐van der Vlis Maria , van Leeuwen‐Cornelisse Inge , Roos Raymund A. C. , Pearson Peter L. , van Ommen Gert‐Jan B.
Published: June 2005

Presymptomatic testing, prenatal diagnosis, or exclusion testing are now available for persons at risk for Huntington disease. These tests will reduce uncertainty, assist in life planning, and prevent the birth of potentially affected children. We present the results of presymptomatic tests for 37 applicants including two prenatal and one exclusion test in 23 families. We initially used the markers G8, H5.52, F5.53, and pTV20 (D4S10), p8 (D4S62), and pRB1.6 (D4S81) and extended the informativity of the test at a later stage with the markers pKP1.65, C4H, S1.5 (D4S43), 674 (D4S95), 157.9 (D4S111), and YNZ32 (D4S125). Applicants with an unsuitable family structure were not admitted to the test. Of the 37 applicants, 33 were informative.

In our hands the most efficient strategy is first to use the markers H5.52 (D4S10), pRB1.6 (D4S81), 674 (D4S95), pKP1.65 (D4S43), 157.9 (D4S111), YNZ32 (D4S125), and 252.3 (D4S115). The overall informativity in our data set was 84% and in the most recent test we achieved a 90–95% informativity. The other markers are used only when the first set is not informative.
Short rib syndrome Beemer‐Langer type with polydactyly: A multiple congenital anomalies syndrome
Authors: Yang S. Samuel , Roth Joel A. , Langer Leonard O.
Published: June 2005

A male fetus with short rib (polydactyly) syndrome, Beemer‐Langer type was aborted at 30 weeks' gestation because of abnormalities visualized on sonography. This is the first documented case with polydactyly in this recently defined entity. The clinical, radiological, and pathological findings, especially of the bones, are described. The differential diagnosis of this entity is discussed.
Beemer‐Langer syndrome with manifestations of an orofaciodigital syndrome
Authors: Lin Angela E. , Doshi Nalini , Flom Lynda , Tenenholz Beverly , Filkins Karen L.
Published: June 2005

We report on an infant girl with hydrops, macrocephaly, high forehead, flat face, hypertelorism, broad nasal bridge, median cleft lip and alveolar ridge, grooved palate, accessory frenula, small tongue, milia, severe rib and limb shortness, brachydactyly, talipes equinovarus, Dandy‐Walker malformation, accessory spleen, unfixed mesentery, ectopic pancreas, and renal cysts. This patient resembles seven previously reported patients with the Beemer‐Langer syndrome, a distinct lethal short rib syndrome characterized by hydrops, markedly short ribs and limbs, median cleft lip with or without cleft palate, flat face, and macrocephaly. Polydactyly is usually absent. Our patient's oral anomalies suggest an orofaciodigital syndrome, but the severe rib and limb shortness distinguish it from those disorders.
Duplication of the distal part of the long arm of chromosome 1
Authors: Johnson Virginia P.
Published: June 2005

A case of dup(1)(q42 → qter) is reported. A literature review of duplication of the distal third of chromosome 1 with breakpoints at various sites, 1q23, 1q25, 1q32, and 1q42, was undertaken. Clinical similarities and differences based on the size of the duplicated segment and other associated deficiencies are summarized.
New clinical aspects of hereditary mucoepithelial dysplasia
Authors: Urban M. D. , Schosser R. , Spohn W. , Wentling W. O. , Robinow M.
Published: June 2005

Hereditary mucoepithelial dysplasia (HMD) is a multiepithelial disorder. It is transmitted as an autosomal dominant trait (McKusick: Mendelian Inheritance in Man—Catalogs of Autosomal Dominant, Autosomal Recessive, and X‐Linked Phenotypes, 8th edition. Baltimore: The Johns Hopkins University Press, pp 499, 1988).

HMD is characterized by variable combinations of lesions of skin, hair, orificial mucosa, gingiva, eyes, and lungs. In some previously described patients, the corneal and pulmonary lesions were progressive and led to blindness, recurrent pneumonia, and/or premature death. On light microscopy, the lesion is characterized by dyskeratosis and, on electron microscopy, by a paucity of gap junctions and desmosomes.

Here, we describe a new 5′generation kindred in which affected individuals had the same histologic characteristics but a some‐what different clinical spectrum and a more benign course. HMD should be considered in the differential diagnosis of childhood alopecia, follicular hyperkeratosis, keratoconjunctivitis, juvenile cataracts, gingival hyperemia, restrictive lung disease, and esophageal stenosis or webs.
Familial translocation 5;14 resulting in an unbalanced offspring
Authors: Park Jonathan P. , Edwards Matthew J. , Moeschler John B. , Marin‐Padilla J. Miguel , Berg Susan Z. , Wurster‐Hill Doris H.
Published: June 2005

We report on an infant with multiple congenital anomalies possessing a derivative 14 chromosome in excess of the normal complement, resulting from transmission of a familial t(5;14)(p13;q22). The proposita's phenotypically normal mother, mentally retarded half‐brother, and fetal sib are carriers of the apparently balanced translocation. Previous cases of similar familial t(5;14) are reviewed. The proposita's phenotype is characterized by failure to thrive, developmental retardation, cleft palate, congenital heart anomaly, abnormal hands and feet, unusual face with abnormal ears, and recurrent respiratory infections. The proposita died at age 9 months and postmortem examination showed multiple central nervous system, cardiopulmonary, gastrointestinal, and genital malformations. Our proposita's phenotype is attributable to contributions from both chromosomes and is consistent with the consequences of both the dup(5p) and dup(14q).
The Noonan‐CFC controversy
Authors: Neri Giovanni , Zollino Marcella , Reynolds James F.
Published: June 2005

The Noonan syndrome and the cardio‐facio‐cutaneous (CFC) syndrome have been described as phenotypically and genetically distinct entities. However, the resemblance between them led some authors to question the validity of this separation. We review available clinical evidence to support the opposite view, namely, that the Noonan and CFC syndromes are indeed distinct and separate conditions, both falling within the broad and causally heterogeneous spectrum of the Noonan/congenital lymphedema phenotype.
Historical study: Johann Gregor Mendel 1822–1884
Authors: Weiling Franz
Published: June 2005

The life and personality of Johann Gregor Mendel (1822–1884), the founder of scientific genetics, are reviewed against the contemporary background of his times. At the end are weighed the benefits for Mendel (as charged by Sir Ronald Fisher) to have documented his results on hand of falsified data.

Mendel was born into a humble farm family in the “Kuhländchen”, then a predominantly German area of Northern Moravia. On the basis of great gifts Mendel was able to begin higher studies; however, he found himself in serious financial difficulties because of his father's accident and incapacitation. His hardships engendered illness which threatened continuation and completion of his studies until he was afforded the chance of absolving successfully theological studies as an Augustinian monk in the famous chapter of St. Thomas in Altbrünn (Staré Brno).

Psychosomatic indisposition made Mendel unfit for practical pastoral duties. Thus, he was directed to teach but without appropriate state certification; an attempt to pass such an examination failed. At that point he was sent to the University of Vienna for a 2‐year course of studies, with emphasis on physics and botany, to prepare him for the exam. His scientific and methodologic training enabled him to plan studies of the laws of inheritance, which had begun to interest him already during his theology training, and to choose the appropriate experimental plant.

In 1865, after 12 years of systematic investigations on peas, he presented his results in the famous paper “Versuche über Pflanzenhybriden.” Three years after his return from Vienna he failed to attain his teaching certification a second time. Only by virtue of his exceptional qualifications did he continue to function as a Supplementary Professor of Physics and Natural History in the two lowest classes of a secondary school. In 1868 he was elected Abbot of his chapter, and freed from teaching duties, was able to pursue his many scientific interests with greater efficiency. This included meteorology, the measurement of ground water levels, further hybridization in plants (a.o. involving the hawk week Hieracium up to about 1873), vegetable and fruit tree horticulture, apiculture, and agriculture in general. This involved Mendel's active participation in many organizations interested in advancing these fields at a time when appropriate research institutes did not exist in Brünn. Some of the positions he took in his capacity of Abbot had severe repercussions and further taxed Mendel's already overstressed system. The worst of these was a 10‐year confrontation with the government about the taxation of the monastery. Attempts to conciliate (a.o. by appointing Mendel first as Vice‐Director, then as Director of the Mora‐vian Mortgage Bank) did not alter Mendel's position.

The recently‐dated genetic note‐sheet shows that Mendel was preoccupied with the interpretation of the results of his Pisum experiments till the end of his life.
Interstitial deletion of 4(q21q25) in a liveborn male
Authors: Rose Nancy C. , Schneider Adele , McDonald‐McGinn Donna M. , Caserta Christine , Emanuel Beverly S. , Zackai Elaine H.
Published: June 2005

We describe a liveborn male with a de novo deletion of 4(q21q25). The findings in this infant are compared with those of other 4q interstitial deletion patients with similar breakpoints. Given the reproducible findings including skull asymmetry, cardiac defects, renal cysts, “butterfly” vertebrae, as well as a particular dysmorphic face with developmental delay, there is evidence for an interstitial 4q deletion syndrome.
Trisomy 14 mosaicism in a 5‐year‐old boy
Authors: Vachvanichsanong Prayong , Jinorose Uraiwan , Sangnuachua Pantipya
Published: June 2005

We report on a 5‐year‐old boy with failure to thrive, mental retardation, a broad nose, hypertelorism, slight antimongoloid slant palpebral fissures, mild ptosis, microphthalmia, short and wide neck, apparently acyanotic tetralogy of Fallot, dislocation of the left hip, generalized linear and patchy hyperpigmentation, micropenis, and undescended testes. He had mosaicism of 46,XY/47,XY, + 14 in a ratio of 3:1. Comparisons are made with the other reports of trisomy 14 mosaicism and relationship to incontinentia pigmenti.
Newly recognized syndrome of cerebral, ocular, dental, auricular, skeletal anomalies: CODAS syndrome—a case report
Authors: Shebib Souheil M. , Reed Martin H. , Shuckett E. Paul , Cross Howard G. , Perry John B. , Chudley Albert E.
Published: June 2005

We report on a child with a unique constellation of congenital anomalies suggesting a new syndrome. These consist of developmental delay; craniofacial abnormalities, including bilateral cataracts, ptosis, median nasal groove, malformed ears with associated neurosensory hearing loss; dental anomalies consisting of anomalous cusp morphology with unusual pointed extensions and delayed tooth eruption; short stature with marked delay in epiphyseal ossification; coronal clefts involving vertebrae T11‐S2; and dislocated hips. A literature search and use of a computer‐assisted syndrome‐identification program failed to uncover an identical case.
Acrocallosal syndrome: A new case
Authors: Lungarotti M. Serena , Marinelli Doretta , Mezzetti Daniele , Caputo Nevia , Calabro Anna
Published: June 2005

We describe a 2‐month‐old infant girl with typical clinical manifestations of the acrocallosal syndrome: characteristic face, agenesis of corpus callosum, polydactyly associated with other anomalies of the extremities, and mental retardation. The importance of a correct nosology and genetic counseling is underlined on the basis of the description of familiar cases of the syndrome.
On the inheritance of primary spontaneous pneumothorax
Authors: Abolnik Igor Z. , Lossos Izidore S. , Zlotogora Joel , Brauer Raphael
Published: June 2005

We report on 15 families with familial primary spontaneous pneumothorax detected through a retrospective study of a large group of male patients. Genetic analysis of these families together with 14 families from the literature in which enough details were available suggested 2 possible models of inheritance.

First, the familial cases are due to an autosomal dominant gene with incomplete penetrance, the penetrance being lower in females (21%) than in males (50%).

Second, the familial cases represent a heterogeneous group of patients: some of the familial cases are due to an X‐linked recessive gene and others to an autosomal dominant gene with the incomplete penetrance (35% in females and 50% in males).

The second model may explain the excess of female carriers found in the families of the patients and is supported by the existence of clinical differences between the patients in each of the sub‐groups. In particular the number of episodes of pneumothorax per patient was significantly higher in the subgroup with the autosomal dominant form than in the sub‐group with the X‐linked recessive form of the disease.
Applications of the concept of attributable fraction in medical genetics
Authors: Khoury Muin J. , Beaty Terri H. , Cohen Bernice H.
Published: June 2005

Attributable fraction, the fraction of cases of a disease in a population attributed to a particular risk factor, is a useful measure in the design and interpretation of epidemiologic studies of disease etiology. We review here the applications of the concept of attributable fraction in medical genetics. Specifically, attributable fraction can be used 1) in studies of the association between genetic traits and specific diseases to quantitate the contribution of specific alleles to disease occurrence in a population; 2) in population studies of mutations and birth defects to estimate the impact of mutagens and teratogens; and 3) in genetic analyses of family data, to evaluate the contribution of putative single gene loci to disease etiology. In the latter context, the concept of attributable fraction can be contrasted with the more commonly used concept of heritability. Examples from the literature provide illustrations of the usefulness of attributable fraction in medical genetic studies.
New syndrome? Osteochondrodysplasia with rhizomelia, platyspondyly, callosal agenesis, thrombocytopenia, hydrocephalus, and hypertension
Authors: Faye‐Petersen Ona Marie , Ward Ken , Carey John C. , Knisely A. S.
Published: June 2005

A female infant born at term to phenotypically normal nonconsanguinous parents had hypertension, thrombocytopenia, hydrocephalus, callosal agenesis, and nonlethal rhizomelic osteochondrodysplasia. Her osteochondrodysplasia was characterized roentgenographically by shortening and metaphyseal broadening of long bones, without bowing, and by platyspondyly, with deficient ossification of dorsal and central portions of vertebral bodies. By light microscopy, the iliac crest growth plate showed expansion of the zone of chondrocyte hypertrophy and degeneration, with faulty columnar alignment, sparse vascular ingrowth, and irregular mineralization at the zone of chondroosseous transformation. These findings appear to define a novel osteochondrodysplasia, which in association with hypertension, thrombocytopenia, hydrocephalus, and callosal agenesis may constitute a new syndrome.
Di George anomaly associated with a de novo Y;22 translocation resulting in monosomy del(22)(q11.2)
Authors: Lupski James R. , Langston Claire , Friedman Richard , Ledbetter David H. , Greenberg Frank
Published: June 2005

We report on an infant, born to a diabetic mother, who presented with hypocalcemia and congenital heart disease, presurgically diagnosed by echocardiography as truncus arteriosus type I. Cytogenetic analysis showed a 45,X, −Y, −22, + der‐(Y)t(Y;22) (p11.3q11.2) chromosome abnormality with del(22)(q11.2). Parental chromosomes were normal. Autopsy showed persistent truncus arteriosus type II and thymic aplasia consistent with DiGeorge anomaly. This report adds to the existing literature demonstrating an association between DiGeorge anomaly and monosomy 22q11.
Dietary management reverses grooving and abnormal polarization of hair shafts in argininosuccinase deficiency
Authors: Kvedar Joseph C. , Baden Howard P. , Baden Lynn A. , Shih Vivian E. , Kolodny Edwin H.
Published: June 2005

We have observed that the fragile hair of two untreated patients with argininosuccinic aciduria showed abnormal alternating zones of bright and dark banding by polarizing microscopy. Scanning electron microscopy documented discontinuous grooves with a 50 to 100 μm periodicity. Results of amino acid analysis of the hair were essentially normal. After the patients were treated with a lowprotein, arginine‐supplemented diet, the hair assumed a normal appearance. Five patients already treated with diet showed no hair abnormalities. The pathogenesis of the hair changes is unknown, but our findings suggest that products generated in the disease can adversely affect metabolically active tissue such as hair.
Two cases of steroid sulfatase deficiency with complex phenotype due to contiguous gene deletions
Authors: Nishimura Shin‐Ichiro , Masuda Hiroyuki , Matsumoto Takahiko , Sakura Nobuo , Matsumoto Tomoaki , Ueda Kazuhiro
Published: June 2005

We report contiguous gene deletions in the distal short arm of the X chromosome in two patients with ichthyosis, due to steroid sulfatase deficiency, and other complex phenotypes. One patient had chondrodysplasia punctata (CDP) and ichthyosis with a normal chromosome constitution. Another patient had a CDP‐like phenotype, ichthyosis, and hypogonadism. His karyotype was 46, ‐X,Y, + der(X)t(X;Y)(p22;q11). DNA from the two patients was analyzed by Southern blotting using cloned fragments mapped in the Xp21‐Xpter region to investigate gene deletions. DNA from the patient with CDP showed a gene deletion of the STS, DXS31, and DXS89 loci, and DNA from the patient with X‐Y trans‐location lacked fragments of the STS, DXS31, DXS89, and DXS143 loci. These findings suggest that the common deleted region involving the STS locus might have caused the similar phenotypes in both patients.
Partial duplication of Xp: A case report and review of previously reported cases
Authors: Wyandt Herman E. , Bugeau‐Michaud Lucille , Skare James C. , Milunsky Aubrey
Published: June 2005

We report clinical and cytogenetic findings on a 24‐year‐old woman with short stature, irregular menses, and other anomalies suggestive of Ullrich‐Turner syndrome (UTS). Chromosome analysis documented a de novo duplication of Xp21 without any apparent microscopic deletion. DNA studies showed that part of band Xp22.1 is also duplicated. The clinical findings are compared with 5 other patients with dup(Xp).
Apparent late‐onset Cockayne syndrome and interstitial deletion of the long arm of chromosome 10 (del(10)(q11.23q21.2))
Authors: Fryns J. P. , Bulcke J. , Verdu P. , Carton H. , Kleczkowska A. , van den Berghe H.
Published: June 2005

We present the history and data on a 24‐year‐old man with clinical and neurological symptoms similar to the findings in patients with late‐onset Cockayne syndrome.

Prometaphase chromosome studies documented an interstitial 10q211 deletion in all cells. This finding may indicate that the gene for late Cockayne syndrome is at 10q211.
Balanced reciprocal translocation mosaicism: New cases and a literature review
Authors: Farrell S. A.
Published: June 2005

Mosaicism for a balanced reciprocal translocation is uncommon. These two new cases were detected during investigation of infertility and miscarriages. Otherwise, the probands were normal. Of five previously described cases, only one was possibly syndromal. More reports of this class of chromosomal aberration are needed to assess accurately the risk of phenotypic abnormalities.
Fused eyelids, airway anomalies, ovarian cysts, and digital abnormalities in siblings: A new autosomal recessive syndrome or a variant of Fraser syndrome?
Authors: Mena Wahib , Krassikoff Natalie , Philips Joseph B.
Published: June 2005

We describe two siblings of unlike gender born to non‐consanguineous parents, with similar and unique congenital malformations. These include fused eyelids, craniofacial anomalies, ovarian cyst, subglottic stenosis, specific digital abnormalities, and no detected chromosomal abnormality. The specific digital abnormalities in both patients are characterized by extension of metacarpo‐phalangeal joints with flexion of the proximal interphalangeal joint of both index fingers with resulting overlap of the second digit over the third. Similar changes were noted in both second toes. The brain weight of both infants was less than that expected for their birth weights. We reviewed the differential diagnosis of fused eyelids, airway anomalies, and ovarian cysts, and the manifestations resemble those seen in Fraser syndrome. We conclude that the dissimilarities warrant considering that our patients have a distinct autosomal recessive syndrome.
Premutation for the Martin‐Bell syndrome analyzed in a large pedigree segregating also for G6PD‐deficiency. I: A working hypothesis on the nature of the FRAX‐mutations
Authors: Filippi Giorgio , Arslanian Araxy , Dagna‐Bricarelli Franca , Pierluigi Mauro , Grasso Marina , Rinaldi Antoniettina , Rocchi Mariano , Siniscalco Marcello
Published: June 2005

A large Sardinianfamily including 13 Martin‐Bell syndrome (MBS) patients, several instances of normal transmitting males or females, and the G6PD‐Mediterranean mutant segregating in some of its branches, has been thoroughly investigated with the hope of gaining further insight on the nature of the FRAX‐mutation. All the MBS patients and the 15 obligate heterozygous women present in the pedigree could be traced back through their X‐chromosome lineage to the same ancestress, who must have been heterozygous for a silent premutation at the FRAX‐locus. This premutation appears to have turned into a true FRAX‐mutation at least 9 times during the gametogenesis of the ancestress' X‐related descendants of whom four are males. This finding alone suggests that the transition from the FRAX premutation to the true mutation can be the result of intra‐ as well as interchromosomal events. This conclusion is supported by the additional observation that the genetic phase between the FRAX and the G6PD loci remained unaltered when the transition occurred in a repulsion double heterozygote for the premutation and the G6PD‐Mediterranean mutant. The data described are compatible with the hypothesis that MBS patients and normal transmitting males are, respectively, hemizygous for deletion or duplication products generated by aberrant recombination events at a highly recombinogenic site of the region Xq27‐Xqter. The overall message stemming from this report is that no firm conclusion can be drawn on the genetic linkage between the FRAX‐locus and other markers of this region until the nature of the FRAX‐mutations and the mechanism of their occurrence are fully understood.
Extending the Pallister‐Hall syndrome to include other central nervous system malformations
Authors: Finnigan David P. , Clarren Sterling K. , Haas Joel E.
Published: June 2005

Hall‐Pallister syndrome is defined by specific facial anomalies, post axial polydactyly, imperforate anus, and brain anomalies including a rare diencephalic mass, hypothalamic hamartoblastoma. In this article, two patients are described with the usual features of Hall‐Pallister syndrome, including diencephalic anomalies, but without hamartoblastomas. These patients may suggest an appropriate extension of the definition of the Hall‐Pallister syndrome.
New syndrome? Ectrodactyly, retrognathism, abnormal ears, highly arched palate, spina bifida, congenital heart defect, single umbilical artery
Authors: Kasznica John , Carlson J. Andrew , Coppedge David
Published: June 2005

We report a possible new syndrome in a female abortus with the following abnormalities: ectrodactyly limited to the feet, a “simplified” ear pattern, mild retrognathism, highly arched palate, spina bifida of open myelomeningocele type, membranous type ventricular septal defect, and single umbilical artery.
Chromosome 7p – syndrome: Craniosynostosis with preservation of region 7p2
Authors: Aughton David J. , Cassidy Suzanne B. , Whiteman David A. H. , Delach Judith A. , Guttmacher Alan E.
Published: June 2005

Deletion of a portion of the short arm of chromosome 7 is associated with a recognizable phenotype which often includes craniosynostosis. Recent reports have suggested that craniosynostosis occurs only if there is a deletion involving band 7p21 or the segment distal to that band. We report on a boy who had an interstitial deletion of7p, not involving band 7p21 or the segment distal to that band, who nevertheless had craniosynostosis. Thus, it appears that the determination of craniosynostosis in this syndrome is more complicated than has been suggested previously.
Hypomelanosis of ito associated with chromosomal translocation involving Xp11
Authors: Lungarotti M. Serena , Martello Cecilia , Calabro Anna , Baldari Franco , Mariotti Giacomo
Published: June 2005

We report on a 3‐year‐old girl with hypohelanosis of Ito (HI). She has typical skin letions and mild CNS involvement characerized by impaired walking and borderline hental retardation.

Cytogenetic investigation showed a 18/X translocation with breakpoint on Xp11.

This is the sixth case of HI in whcih this reakpoint has been reported, undrlining hat this event cannot be considered coinciental. Further studies are needed to undrtand the etiologic and pathogenetic meaning of this finding.
Neurological aspects of del(1q) syndrome
Authors: Murayama Keiko , Greenwood Robert S. , Rao Kathleen W. , Aylsworth Arthur S.
Published: June 2005

We have studied three children with de novo terminal deletion of the long arm of chromosome 1 (46,XX,del(1)(q43)). They all have minor anomalies and neurological signs (severe psychomotor developmental delay, generalized hypotonia, and seizures) that have been described previously. In addition, all of these three patients have autistic‐like behavior. They avoid eye contact, show no interest in people, express little emotion, and repeat stereotypic movements such as head nodding and purposeless finger manipulation. They also spend excessive time in making unusual sounds consisting of a high‐pitched shrill cry with little intonation in infancy and a harsh, strained, and glottal stridency in later life. They make no labial, lingual, or nasal sounds. We suggest that these observations may be unique clinical manifestations of certain terminal 1q deletions.
Quantitative analysis of associations between birth defects and suspected human teratogens
Authors: Khoury Muin J. , James Levy M. , Lynberg Michele C.
Published: June 2005

Case series of infants with certain birth defect patterns and putative teratogenic exposures should be interpreted with caution since the presence of birth defects and the exposure among the same infants could be entirely due to chance. In the absence of other epidemiologic data, the plausibility for a causal association is strengthened by 1) rarity of the defect pattern, 2) rarity of the exposure in the population, 3) small source population, 4) short time period for the study, and 5) biologic plausibility for the association. These concepts are illustrated using case reports of putative teratogenicity of cocaine and etretinate. In the presence of epidemiologic data, the concept of attributable fraction in exposed (AFE) can be used to evaluate the likelihood that the defect pattern among infants with a particular exposure is attributable to the exposure. This quantity is related to the strength of the epidemiologic association between the defect pattern and the exposure, as measured in terms of relative risk R (or odds ratio), and is equal to (R‐1)/R. Even for strong teratogens such as maternal diabetes and isotretinoin, where R is about 7, in more than 14% (1‐AFE) of exposed infants with birth defects, the pattern of defects is not attributable to the exposure. Furthermore, AFE can be used to “correct” crude measures of sensitivity (the proportion of exposed malformed infants with a defect pattern attributable to the exposure) and positive predictive value (the proportion of malformed infants who have the exposure and have the defect pattern attributable to the exposure). These concepts can be useful adjuncts to the quantitative evaluation of patterns of birth defects associated with suspected human teratogens.
De novo inv(2)(p21q31) associated with isolated bilateral microphthalmia and cataracts
Authors: Weaver R. Grey , Rao Nagesh , Thomas Ioan T. , Pettenati Mark J.
Published: June 2005

We report on a patient with bilateral microphthalmia and unusual cataracts with a de novo pericentric inversion of chromosome (2)(p21q31). A literature review of previous as sociations of eye abnormalities and anomalies of chromosome 2 suggests probable gene locations for eye development.
Protocol for genetic testing in Huntington disease: Three years of experience in Minnesota
Authors: Nance Martha A. , Leroy Bonnie S. , Orr Harry T. , Parker Terry , Rich Stephen S. , Heston Leonard L.
Published: June 2005

Molecular genetic testing for Huntington disease (HD) by linkage analysis of DNA markers close to the HD gene has been possible since the mid‐1980s. Because of ethical and practical concerns about this kind of testing, most groups performing the test in the past have operated under lengthy research protocols designed to assess the psychological morbidity of the presymptomatic diagnosis of a fatal disease. Our approach to HD testing is service‐oriented, and our testing process has been designed to be flexible, to meet the varying needs of our patients. Between 1988 and 1990, 87 inquiries about the test have been received; 22 inquiries had family structures which were unsuitable for linkage analysis. Eleven of the 37 individuals who entered the testing program have not completed it. Of 19 patients who have received DNA results, seven received an increased risk of carrying the HD gene, and ten, a decreased risk. For two additional individuals, nonpaternity resulted in a negligible risk for HD. Several of those consulted, or their spouses, have had continuing outpatient counseling since completing the test; none have required hospitalization. Our short‐term results indicate that molecular genetic testing for HD can be performed safely in a clinical setting using our protocol. As molecular genetic testing for HD and other diseases moves out of research centers and into clinics, clinicians must devise practical strategies for providing the medical, genetic, and psychological services needed for the growing number of individuals who will seek such testing.
Oculodentodigital dysplasia syndrome associated with abnormal cerebral white matter
Authors: Gutmann David H. , Zackai Elaine H. , McDonald‐McGinn Donna M. , Fischbeck Kenneth H. , Kamholz John
Published: June 2005

Oculodentodigital dysplasia (ODDD) syndrome is an uncommon inherited disorder with eye and facial abnormalities, syndactyly, and defects in tooth enamel. Some of the previously reported patients with ODDD syndrome also manifested spastic quadriparesis. We describe a patient with sporadic ODDD syndrome referred for evaluation of progressive spastic paraparesis. Magnetic resonance imaging of the brain demonstrated abnormal white matter, which suggests an explanation for the observed spastic paraparesis.
Limb body‐wall complex in association with sirenomelia sequence
Authors: Tang Thomas T. , Oechler Herbert W. , Hinke David H. , Segura Annette D. , Franciosi Ralph A.
Published: June 2005

Limb body‐wall complex and sirenomelia sequence are uncommon birth defects and their association is extremely rare. Their overlapping manifestations and their concurrence in our patient suggest that they share a common cause and belong to a group of pathologically closely related conditions. Embryonic vascular disruption may be a common pathogenesis in both anomalies.
Neu Laxova syndrome in two Egyptian families
Authors: Meguid Nagwa Abdel , Temtamy Samia A.
Published: June 2005

We report on 2 Egyptian girls from 2 families with 8 affected relatives, 4 in each family. The 2 propositae had unusual facial appearance, severe microcephaly, generalized edema, contractures of limbs, and generalized ichthyotic skin lesions. Findings in the present 2 patients were compared with those in previously reported cases of Neu Laxova syndrome. In our cases, consanguinity, affected sibs, and affected cousins were noted. Autosomal recessive inheritance and lethality are emphasized. A high frequency of the Neu Laxova syndrome in Egyptians is suspected as a result of the increased consanguinity rate.
Genetic and clinical heterogeneity of Stickler syndrome
Authors: Vintiner Gillian M. , Temple I. Karen , Middleton‐Price Helen R. , Baraitser Michael , Malcolm Sue
Published: June 2005

We have studied 6 multigeneration Stickler syndrome families. Manifestations of the syndrome in the families included myopia, deafness, arthritis, characteristic facial changes with “flat” midface and cleft palate, although not all these were present in all families. COL2A1 has been implicated as a gene which can give rise to Stickler syndrome based on evidence from 2 large families which each showed significant linkage between the disease locus and restriction fragment length polymorphisms for the gene (Francomano CA, Lieberfarb RM, Hirose T, Maumenee IH, Streeten EA, Meyers DA, Pyeritz RE (1987): Genomics 1:293–296; Knowlton RG, Weaver EJ, Struyk AF, Knobloch WH, King RA, Norris K, Shamban A, Uitoo J, Jimenez SA, Prockop DJ (1989): Am J Hum Genet 45:681–688). We have found crossovers between the disease locus and COL2A1 in 2 families with Stickler syndrome. This could be explained by either genetic heterogeneity or the actual mutation being in a closely linked, currently unrecognized gene. We found a weakly positive overall lod score (z = 0.96 at θ = 0.10) suggesting that genetic heterogeneity is a more likely explanation. In one family, with typical findings, a translocation t5;17 (q15:q23) was found to segregate with the disease in 4 affected relatives. In view of the possible heterogeneity, although no crossovers with COL2A1 were seen in this family, either of these breakpoints could be the position of a further disease causing gene.
Human chorionic gonadotrophin and trisomy 18
Authors: Barkai G. , Chaki R. , Sochat M. , Goldman B.
Published: June 2005

Estimation of maternal serum β‐CG is used in conjunction with α‐fetoprotein (AFP) and estriol (E3) for estimating the risk of Down syndrome (DS) affected fetuses. However, low hCG levels have not been regarded as having clinical significance. We report on 2 patients with trisomy 18 fetuses in whom antenatal screening showed extremely low hCG levels (0.05 and 0.15 MOM). Low hCG levels might indicate increased risk for trisomy 18 despite low estimated risk for DS.
Hypomandibular faciocranial dysostosis: Report of an affected sib and follow‐up
Authors: Schimke R. Neil , Claflin Katherine S. , Seguin John H. , Bennett Timothy L. , Finley Brent E. , Levitch Lenna M. , Newcomb Ward M.
Published: June 2005

Hypomandibular faciocranial dysostosis is a condition heretofore described only in a single case. We report the birth of an affected sister along with follow‐up information on the initial surviving patient. While a primary error in neural crest development was postulated in this syndrome, subsequently discovered anatomical abnormalities suggest a more complex pathogenesis.
Research studies in applied human genetics: A quantitative analysis and critical review of recent literature
Authors: Lippman A.
Published: June 2005

To determine the extent to which speculations about the social, legal, and ethical implications of genetic counseling, screening, and prenatal diagnosis are being studied empirically, the substantive contents of major genetics (N=5) and obstetrics journals (N=2) from the years 1985–1989 were reviewed. Among the approximately 9,000 articles published, only 58 containing relevant substantive data could be identified. Data collected in a single study were reported in more than one article in at least ten cases so that these articles actually represent only 45 distinct studies. Most described investigations of the attitudes and reactions of individuals or couples who had had had or been referred for genetic counseling or prenatal diagnosis. These observational studies generally employe study‐specific questionnaires, many of which were apparently self‐administrered by respondents, to obtain data. This survey and analysis of the recent literature suggests that despite frequent editorials and othelr commentaries underlining the problematic nature of developments in medical genetics and calling for their investigation, the “gatekeepers” to this service continue to pay scant attention to these issues in their reported research. Innovative and interdisciplinary studies that will provide information to close the many gaps in ourunderstanding of the consequences of developments in applied human genetics are recommended for the furture.
Sacrococcygeal dysgenesis association
Authors: Duncan Peter A. , Shapiro Lawrence R. , Klein Robert M.
Published: June 2005

In the malformation analysis of 445 patients ascertained only for a sacrococcygeal malformation, a new phenotype, the sacrococcygeal dysgenesis association (SDA), was delineated in 34%. In addition, sirenomelia patients were found in 12%, the VATER association in 27%, and 27% could not be classified. Heterogeneity in the patients with sacrococcygeal malformations was identified by the differences found in their associated malformations.

SDA patients have a relatively small average number (3.3) of anomalies per patient as compared with 9.3 in sirenomelia and 6.2 in VATER patients. SDA abnormalities occurred to a significant degree only in 6 of 20 designated malformation categories (vertebral, rib, pelvic, lower limb, central nervous system [CNS], renal) in contrast to 17 in VATER and 18 in sirenomelia patients. The SDA vertebral malformation pattern also differed from that of VATER/sirenomelia patients as did the high sacrococcygeal agenesis: dysgenesis ratio and low thoracolumbar vertebrae and/or rib hypersegmentations. Most significantly, SDA patients had a large number of CNS anomalies and CNS‐related dysfunctions of the urinary and distal intestinal tracts but no anatomic urinary or intestinal tract malformations. This contrasted sharply with the markedly increased occurrences of anatomic abnormalities in these body regions of the sirenomelia and VATER patients.

Demographic data such as patient survival, twinning and, particularly, the high (28%) incidence of maternal diabetes in the SDA further support its differentiation from VATER/sirenomelia patients.
Diagnosis of tetrasomy 18p using in situ hybridization of a DNA probe to metaphase chromosomes
Authors: Park Vicki Murtif , Gustashaw Karen M. , Bilenker Robert M. , Golden Wendy L.
Published: June 2005

We identified an isochromosome of 18p [47, XY, + i(18p)] conclusively by in situ hybridization of an 18p‐specific probe (B74; D18S3) to metaphase chromosomes of an affected patient. Clinical findings included mental retardation, microcephaly, and an atrial septal defect. Although there is similarity to patients previously described with tetrasomy 18p, it is impossible to rule out a low frequency of mis‐diagnoses in karyotypes determined solely by standard cytogenetic analyses. We expect the ability to conclusively identify an i(18p) to lead to the delineation of tetrasomy 18p as a distinct clinical syndrome.
Weaver syndrome in two Japanese children
Authors: Kondo Ikuko , Mori Yuhko , Kuwajima Katsuko
Published: June 2005

We report on 2 Japanese patients (a 3‐year‐old girl and an 20‐month‐old boy) with the Weaver syndrome. The clinical manifestations are mild mental retardation, overgrowth with accelerated bone age, minor facial anomalies including broad forehead, mild hypertelorism, depressed nasal bridge, accentuated philtrum, micrognathia and large ears, and unique behavior characteristics with some social withdrawal. The nosology of the Weaver and Simpson–Golabi–Behmel syndromes is discussed.
Monozygotic twins of discordant sex both with 45, X/46, X, idic(Y) mosaicism
Authors: Fujimoto Atsuko , Boelter William D. , Sparkes Robert S. , Lin Ming S. , Battersby Kathleen
Published: June 2005

A female twin with short stature, unusual facial appearance, widely spaced nipples, and coarctation of the aorta was found to have a peripheral blood lymphocyte karyotype of 45, X(43%)/46, X, idic(Y)(p11). Her twin brother, also short with similar facial appearance, had the same mosaicism (40% 45, X). Cultured skin fibroblast studies showed discrepant karyotypes of 45, X (100%) in the girl and 45, X (78%)/46, X, idic(Y)(p11) in the boy. The mother and the father had normal chromosomes. Comparison of 27 biochemical markers yielded a likelihood of monozygosity of 0.9977. This report documents the occurrence of discordant phenotypic sex in monozygotic twins, involving gonadal dysgenesis with an abnormal dicentric Y, which presumably occurred de novo, followed by anaphase lag probably before the occurrence of twinning. Unequal distribution of the two resultant cell lines in various tissues of each twin could account for the development of the very different phenotypes, apparently normal boy and Ullrich‐Turner girl.
Association of the Robin sequence with the fragile X syndrome
Authors: Lachiewicz Ave M. , Hoegerman Stanton F. , Holmgren Gösta , Holmberg Eva , Arinbjarnarson Kristian
Published: June 2005

We report on 4 individuals with the fragile X [fra(X)] syndrome and the Robin sequence (or elements of that sequence). To our knowledge, this association has been described in only one other boy. However, males with the fra(X) syndrome have been reported to have an increased incidence of cleft palate. We recommend that children with a cleft palate or the Robin sequence be assessed for developmental delays and a family history of mental retardation. The fra(X) syndrome may be one of the genetic causes of the Robin sequence and, when indicated, children with the sequence should be tested for fra(X).
Estimated number of loci for autosomal recessive severe nerve deafness within the Israeli Jewish population, with implications for genetic counseling
Authors: Brownstein Zipora , Friedlander Yechiel , Peritz Eric , Cohen Tirza
Published: June 2005

Deafness occurs in about 1 per thousand live births, and at least 50% of congenital deafness is hereditary. The aim of this study was to examine the number of loci for recessively in herited severe nerve deafness of early onset within the Israeli population and to compare the results to those obtained in other populations. The Jewish population in Israel originates from many countries and may be divided into Sephardi, Eastern and Ashkenazi Jews, and the matings will be intraethnic or interethnic. Data were obtained on 133 deaf couples who lived in the Tel Aviv area, through the files of the Helen Keller Center. Causes of deafness in the spouses were studied and data on their children were obtained. Among 111 couples who had recessive or possibly recessive deafness and had at least 1 child, there were 12 with only deaf children and 5 with both deaf and hearing children. The number of loci for recessive deafness in the whole group was estimated at 8–9. Intraethnic and interethnic matings gave an estimate of 6.7 and 22.0 loci, respectively, which indicates that within populations fewer loci exist with recessive mutations for deafness than between populations. it could be shown that the sharing of loci between spouses decreased with increasing geographical distance of their origin. The results provide data for genetic counseling in Israel for deaf couples who have no children or have one hearing or one deaf child.