bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations in the COL1A2 gene of type I collagen that result in nonlethal forms of osteogenesis imperfecta
Authors: Wenstrup Richard J. , Lever Laura W. , Phillips Charlotte L. , Quarles L. Darryl
Published: June 2005

Although virtually all mutations that result in osteogenesis imperfecta (OI) affect the genes that encode the chains of type I procollagen, the effects of mutations in the COL1A2 gene have received less attention than those in the COL1A1 gene. We have characterized mutations in 4 families that give rise to different OI phenotypes. In three families substitutions of glycine residues by cysteine in the triple helical domain (a single example at position 259 and 2 families in which substitution of glycine at 646 by cysteine) have been identified, and in the fourth a G for A transition at position + 4 in intron 33 led to use of an alternative splice site and inclusion of 6 amino acids (val‐gly‐arg‐ile‐leu‐phe) between residues 585 and 586 of the normal triple helix. The relation between position of substitution of glycine by cysteine in the COL1A2 gene does not follow the pattern developed in the COL1A1 gene. To determine how COL1A2 mutations produce OI phenotypes, we have produced a full‐length mouse cDNA into which we plan to place mutations and examine their effects in stably transfected osteogenic cells and in transgenic animals.
Chemical cleavage method for the detection of RNA base changes: Experience in the application to collagen mutations in osteogenesis imperfecta
Authors: Bateman John F. , Lamande Shireen R. , Hannagan Marnie , Moeller Ingrid , Dahl Hans‐Henrik M. , Cole William G.
Published: June 2005

We discuss the definition of mutations in osteogenesis imperfecta (OI) using a chemical cleavage method for detecting mismatched bases in patient mRNA: control cDNA hetero‐duplexes. The method is based on the increased chemical modification of cytosines (Cs) by hydroxylamine and thymines (Ts) by osmium tetroxide when they are not paired with their complementary base. The DNA is then cleaved at the modified base with piperidine and the use of radioactively labeled DNA probes allows the position of the mismatched base to be determined by electrophoresis of the cleavage‐product. The precise mutations are then determined by specific amplification and sequencing of the region containing the mismatched base. In perinatally lethal OI (OI type II) mismatches have been detected in all 17 cases studied; 12 of these have been fully characterized. In 7 of these 12 cases the mismatches were point mutations in the genes for proα1(I) or proα2(I) which resulted in glycine substitutions in the triple helical region of the protein. Sequence variation was detected in addition to the glycine substitutions in 2 cases. In 2 cases the RNA mismatch resulted from changes in the amino acid sequence of the C‐propetide domain. In the 3 remaining cases the mismatch resulted from silent nucleotide sequence variants. In the less severe forms of OI we have studied, mismatches have been detected and characterized in 8 of 12 cases. In 4 of these 8 cases the mismatch resulted from presumably neutral sequence variation and in the other 4 cases mutations have been defined.

Three of these were also glycine substitutions in the α1(I) or α2(I); and in one case, 014, the mutation was the deletion of exon 8 in the α1(I) seqence.
Moderately severe osteogenesis imperfecta associated with substitutions of serine for glycine in the α1(I) chain of type I collagen
Authors: Marini Joan C. , Lewis Mary Beth , Chen Kathleen
Published: June 2005

We have examined the type I collagen protein, RNA, and cDNA of 2 children with moderately severe (type IV) osteogenesis imperfecta (OI). They have in common a non‐lethal form of OI with ambulatory potential, over‐modification of type I collagen protein, and a substitution of serine for glycine in the collagen chain produced by one α1(I) allele.

The first child (Marini et al.: J Biol Chem 264:11893‐11900, 1989) is now 7 years old, with the height of a 3‐year‐old. Her course includes significant remodeling of lower long bones and 4 femur fractures. She walks independently. A mishmatch was detected in her α1(I) mRNA using RNA/RNA hybrids; it was demonstrated to be due to a G→A point mutation in one allele of α1(I), resulting in the substitution of serine for glycine 832.

The second child is now 6½ years old, with the height of 1½‐year‐old. Her history includes significant bowing of femurs and tibias, 6 femur fractures, S‐curve scoliosis, compression of all lumbar vertebrae, and limited short‐distance walking with braces. Her α1(I) mRNA has also been studied by RNA hybrid analysis; there is a single G→A change in one α1(I) allele causing the substitution of serine for gly 352.

Both children have moderately severe OI. However, the serine substitution at gly 352 is associated with a more severe phenotype then is the serine substitution at gly 832. Compared to substitutions described in other cases of OI, the serine 352 is located in the middle of a cluster of cysteine substitutions associated with non‐lethal OI. The ser 832 is located near another non‐lethal substitution of serine for glycine but is otherwise flanked by lethal sub‐stitutions. These data support a model of OI cause in which crucial and non‐crucial regions are interspersed along the type I collagen chain. Whether a mutation located in a particular region causes OI type II or OI type IV would then depend on the importance of that region for the interaction of type I collagen with other matrix components or for intracellular processing.
Immunohistochemical localization of interstitial collagens in bone tissue from patients with various forms of osteogenesis imperfecta
Authors: Nerlich Andreas G. , Brenner Rolf E. , Wiest Irmgard , Lehmann Hartwig , Yang Chunlin , Müller Peter K. , von der Mark Klaus
Published: June 2005

Immunohistochemical studies of bone from individuals with osteogenesis imperfecta (OI) type II, OI type III, or OI type IV demonstrate a similar pattern, but varying extent, of the abnormal presence of interstitial collagens in bone matrix. OI type II bone had nests of cartilage with type II collagen, and significant type III collagen in the bone matrix. In OI types III and IV, type II collagen was present only in epiphyseal cartilage but bone still contained type III collagen. These findings resembled those in developing fetal bone indicating the “immature” nature of OI bone.
Osteogenesis imperfecta and hyperplastic callus formation: Light‐ and electron‐microscopic findings
Authors: Stöss H. , Pontz B. , Vetter U. , Karbowski A. , Brenner R. , Spranger J.
Published: June 2005

In rare cases of osteogenesis imperfecta, an “overshoot” growth of new bone may occur, which, clinically gives the impression of a tumour. This condition is known as hyperplastic callus formation. Morphology showed an excessive mixed desmal‐chondral osteoneogenesis. Atypical collagen fibrils in non‐callus tissue represent an indicator for this callus formation in individual patients.
Fragilitas ossium (fro/fro) in the mouse: A model for a recessively inherited type of osteogenesis imperfecta
Authors: Sillence D. O. , Ritchie H. E. , Dibbayawan T. , Eteson D. , Brown K.
Published: June 2005

The fragilitas ossium (fro/fro) in the mutation in the mouse has been demonstrated to have clinical, radiographic and morphologic manifestations similar to those which arise in autosomal recessive forms of osteogenesis imperfecta (OI) occurring in humans. Approximately 90% of mutant offspring in the mouse were perinatally lethal with clinical and roentgenographic findings similar to those of OI type II subgroup A in humans. The 10% of mutant mice surviving follow a course very similar to severe progressively deforming OI type III. In surviving mice, there is progressive fore‐limb and hind‐limb bowing in the absence of a high fracture frequency.
Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis
Authors: Cohen M. Michael
Published: June 2005

Seven Pfeiffer syndrome pedigrees (three 3 generation and four 2 generation) have been recorded to date in addition to at least a dozen sporadic cases. Autosomal dominant inheritance with complete penetrance is characteristic of the 7 familial instances. Variable expressivity has involved mostly the presence or absence of syndactyly and the degree of syndactyly when present.

Classic Pfeiffer syndrome is designated type I. Type 2 consists of cloverleaf skull with Pfeiffer hands and feet together with ankylosis of the elbows. Such patients do poorly with an early death. All reported instances to date have been sporadic. Type 3 is similar to type 2 but without cloverleaf skull. Ocular proptosis is severe in degree and the anterior cranial base is markedly short. These patients also do poorly and tend to have an early death. To date all cases have occurred sporadically.

Although these 3 clinical subtypes do not have status as separate entities, their diagnostic and prognostic implications are important. Type 1 is commonly associated with normal intelligence, generally good outcome, and can be found dominantly inherited in some families. Types 2 and 3 generally have severe neurological compromise, poor prognosis, early death, and sporadic occurrence. Recognition of type 3 is particularly important because extreme ocular proptosis in the absence of cloverleaf skull but with various visceral anomalies can result in failure to diagnose Pfeiffer syndrome and labeling the patient as an “unknown” or as a “newly recognized entity.” The major diagnostic clues in type 3, as well as in the other clinical subtypes, remain classic Pfeiffer hands and feet in association with craniosynostosis, regardless of craniofacial variability or the presence or absence of visceral anomalies.

A ratio of hallucal width to second toe width is developed to provide guidelines for what constitutes a broad great toe in Pfeiffer syndrome. Cases that do not qualify as examples of Pfeiffer syndrome are then reviewed. © 1993 Wiley‐Liss, Inc.
Velo‐cardio‐facial syndrome: A review of 120 patients
Authors: Goldberg Rosalie , Motzkin Beth , Marion Robert , Scambler Peter J. , Shprintzen Robert J.
Published: June 2005

A series of earlier reports has described the velo‐cardio‐facial syndrome (VCFS), a syndrome of multiple anomalies including cleft palate, heart malformations, facial characteristics, and learning disabilities. The patients reported previously were primarily ascertained from a craniofacial program at a large tertiary medical center. Recent reports, including a companion paper in this issue, suggest that this common syndrome of clefting is also a common syndrome of congenital heart defect (CHD) which is expressed as familial examples of DiGeorge sequence. Appreciation of more severely affected cases of VCFS and the detection of mild expressions have led to a broadening of the phenotypic spectrum of the syndrome. The purpose of this report is to describe the full spectrum of VCFS, including several new manifestations and to compare the VCFS phenotype with published cases of “familial DiGeorge sequence” which are now thought to represent examples of VCFS. © 1993 Wiley‐Liss, Inc.
Trimethylaminuria in a girl with Prader‐Willi syndrome and del(15)(q11q13)
Authors: Chen Harold , Aiello Frank
Published: June 2005

We report on an individual with trimethyl‐aminuria, Prader‐Willi syndrome, and del(15) (q11q13). To our knowledge, such an association has never been reported. Skin sores secondary to choline‐rich foods and amenable to dietary control have not been described in trimethylaminuria, although they are seen in some patients with Prader‐Willi syndrome. Pathogenesis, clinical diagnosis, and management of reported cases with trimethylaminuria are reviewed.

Serious social and behavioral problems may result from strong body odor. Amelioration of the “fish odor” by dietary choline restriction makes trimethylaminuria detection important. Association of trimethylaminuria with Prader‐Willi syndrome and del(15) (q11q13) in this patient is of particular interest. It may represent a contiguous gene syndrome, or deletion of the normal allele leading to expression of a single recessive trimethylaminuria gene, or an unrelated association, such as in Noonan syndrome. However, recent development of mapping of flavin‐containing monooxygenase 2 (FMO2), the likely enzyme that is defective in fish odor syndrome, to chromosome 1q probably excludes pathogenetic association of fish odor syndrome with the Prader‐Willi syndrome. © 1993 Wiley‐Liss, Inc.
Microcephaly and digital anomalies: A newly recognized syndrome of recessively inherited mental retardation
Authors: Kelly Thaddeus E. , Kirson Lisa , Wyatt Jo
Published: June 2005

We describe 2 brothers with congenital microcephaly and moderately severe mental retardation. The presence of identical and symmetrical digital anomalies suggests that this constellation represents a clinically recognizable recessively inherited mental retardation syndrome. Recognition of the clinical diagnosis should provide accurate genetic counseling to parents of a single affected child. © 1993 Wiley‐Liss, Inc.
Syndrome of cleft palate, microcephaly, large ears, and short stature (Say syndrome)
Authors: Abu‐Libdeh Bassam , Fujimoto Atsuko , Ehinger Marcia
Published: June 2005

In 1975 Say et al. (Humangenetik 26:267–269) reported on a new dominantly inherited syndrome of cleft palate, short stature, microcephaly, large ears, and hand anomalies in 4 members of a family. This is a report of a 13‐month‐old girl with cleft palate, short stature, microcephaly, sparse scalp hair, large abnormally shaped ears, small hands with tapering fingers, delayed bone age, unusual dermatoglyphics, proximal renal tubular acidosis with cystic dysplasia of the kidneys, and developmental delay. This case appears to be the second report of this syndrome which presumably occurred as a new mutation in this family. © 1993 Wiley‐Liss, Inc.
Unbalanced mosaic karyotypes with different structural abnormalities involving a common chromosome region: Report of two cases
Authors: Pettenati M. J. , Teot L. A. , Smith C. , Hayworth R. , Thomas I. T. , Veille J. C. , Rao P. N.
Published: June 2005

We report on 2 cases with different de novo unbalanced mosaic karyotypes in which each cell line had a different structural abnormality involving a common chromosome region: 46,XX,del(11)(q23.3)/46,XX,−11,+der(11)t(11;?)(q23.3;?) and 46,X,idic(Xq)/46,X,idic(Xq),−12,+der(12)t(X;12)(p11.2;p13.3). Molecular‐cytogenetic analysis confirmed the origin of the derivative 12 chromosome in the latter. We present a literature review of reports with mosaic cell lines of structural chromosome abnormalities that share the same chromosome breakpoint. © 1993 Wiley‐Liss, Inc.
Angular homeostasis IX. Polygonal orbits with a moving target: Implications for anomalous numbers of digits in congenital heart disease
Authors: Murphy Edmond A.
Published: June 2005

This paper explores properties of discrete processes in which a pursuer seeks a target that is moving at constant velocity r that is a fixed proportion of the speed of the pursuer. The pursuer is subjected to proportional angular homeostasis, so chosen that the number of steps per circuit is small. The orbits relative to the target may assume any of four forms: polygons that reverse their sense an infinite number of times; or polygons that after a finite number of reversals ultimately come to have an integer numbers of sides; or have a rational numbers of sides; or have an irrational number of sides that densely fill an annulus. None of the polygons is regular. In the parameter space, the boundary line between the first of these sets and the other three has a somewhat bizarre pattern and may possibly be fractal, but no proof is forthcoming. Unlike the pattern with a stationary target, there may be a set or catchment of diverse values of the speed ratio, r, and the correction coefficient, b that all result in figures of some specified number, n, of sides (although with vertices in differing locations). Catchments have been found for only those polygons that have the winding number of 1. The implications are discussed that this property has for the genetic coding of biological traits that are countable. Some attention is also paid to the relevance of polygons with few sides to ontogenic growth when the correction coefficient is cyclically arc‐ or time‐dependent. © 1993 Wiley‐Liss, Inc.
Presymptomatic diagnosis of SMA III by genotype analysis
Authors: Brahe Christina , Zappata Stefania , Velonà Isabella , Bertini Enrico , Servidei Serenella , Tonali Pietro , Neri Giovanni
Published: June 2005

Linkage analysis and prenatal prediction in families segregating autosomal recessive spinal muscular atrophy (SMA) has become feasible since the assignment of the locus responsible for type I‐III SMA to region 5q12‐q13.3. We have performed a segregation study of SMA in Italian families using molecular probes and highly informative PCR‐based polymorphic markers. In one family, a 7‐year‐old boy affected with type III SMA and an 8‐year‐old apparently healthy brother had identical haplotypes. These findings prompted us to reexamine the apparently unaffected child. His neurological exam was normal. However, the electromyography (EMG) showed a pattern consistent with chronic SMA. To our knowledge this is the first example of presymptomatic diagnosis of SMA based on genotype analysis. © 1993 Wiley‐Liss, Inc.
Aase syndrome: Novel radiographic features
Authors: Hing A. V. , Dowton S. B.
Published: June 2005

We report on a female with hypoplastic anemia and abnormally digitalized thumbs who presented with growth failure and novel osseous radiologic abnormalities. In addition to thumb anomalies, abnormalities of the clavicles, ilia, distal sacrum, and coccyx and described. © 1993 Wiley‐Liss, Inc.
Brachymesomelia and Peters anomaly: A new syndrome
Authors: Kivlin Jane D. , Carey John C. , Richey Mark A.
Published: June 2005

We report on a child with an unusual mesomelic bone dysplasia and Peters anomaly. While there is some resemblance to the radiographic findings and corneal clouding described by Pillay in the OMMD (ophthalmomandibulo‐melic dysplasia) syndrome, there are also differences. The several syndromes that combine brachymesomelia and corneal clouding are discussed. © 1993 Wiley‐Liss, Inc.
Photoanthropometric study of facial growth in Noonan syndrome
Authors: Sharland Michael , Morgan Maureen , Patton Michael A.
Published: June 2005

We present a photoanthropometric analysis of 104 individuals with Noonan syndrome. The study contained 53 males and 51 females with an age range of one to 60 years (mean 13.8 years). The results provide an objective evaluation of facial abnormality in Noonan syndrome. Individuals with Noonan syndrome are demonstrated to have an increased mid face height, hypertelorism, retrognathia, a lower nasal bridge and nasal root, a wider mouth, a more prominent upper lip, and apparently lower set ears than normal control individuals. Within the patient group an apparent alteration of facial structure was noted with increasing age, suggesting that remodelling of the characteristic face in Noonan syndrome may occur into adult life. © 1993 Wiley‐Liss, Inc.
Duplication of 9q12‐q33: A case report and implications for the dup(9q) syndrome
Authors: Stalker Heather J. , Aymé Ségolène , Delneste Daniele , Scarpelli Hélène , Vekemans Michel , Der Kaloustian Vazken M.
Published: June 2005

We report on a boy with a direct tandem duplication of 9(q12‐q33) and dolichocephaly, beaked nose with prominent philtrum, deepset eyes, receding small chin, failure to thrive, developmental delay, simian creases, long fingers, stiff joints, and hypoplastic scrotum. This patient is compared to the 5 other reported cases with pure partial dup(9q), and the “trisomy 9q syndrome” described by Turleau et al. [1975]. © 1993 Wiley‐Liss, Inc.
Familial cases of gastroschisis in a population‐based registry
Authors: Torfs Claudine P. , Curry Cynthia J. R.
Published: June 2005

Only a few familial cases of gastroschisis have been reported. Consequently, the risk of a recurrence has been thought to be very small. In a population‐based study of gastroschisis that included an extended pedigree of all probands, 6 (4.7%) out of 127 families had more than one affected relative. The relationships of the affected were: sib, half‐sib (2), first cousin, second cousin once removed, and great uncle. Sib recurrence was 3.5%. Our results suggest that pregnancies occurring in a family with a history of gastroschisis may be at higher risk of recurrence than previously thought. © 1993 Wiley‐Liss, Inc.
Are the Wolffian anomalies in males the phenotype corresponding to the Müllerian anomalies in females?
Authors: Zlotogora JoëL
Published: June 2005

The Wolffian and Müllerian ducts are embryologically closely related. This survey was aimed to determine whether, as has been suggested, Wolffian duct anomalies in males are the phenotype corresponding to Müllerian anomalies in females. This was done by analysis of the phenotype of the males in associations and syndromes in which Müllerian duct anomalies are frequent, and of the phenotype of the females in families in which anomalies of the Wolffian ducts are found. It appears that the only relation between the 2 types of defects seems to be a developmental one. In cases of early insult, anomalies are seen in males and females (e.g., in the association of renal agenesis with Müllerian or Wolffian defects). On the other hand, in all the other associations or syndromes, no relation was observed. This suggests that Wolffian anomalies in males are not the phenotype corresponding to Müllerian anomalies in females. © 1993 Wiley‐Liss, Inc.
Association between alleles of the transforming growth factor‐alpha locus and the occurrence of cleft lip
Authors: Sassani Russell , Bartlett Scott P. , Feng Hongshu , Goldner‐Sauve Audrey , Haq Asifa K. , Buetow Kenneth H. , Gasser David L.
Published: June 2005

DNA samples from 100 patients with cleft lip with or without cleft palate (CL/P) were compared with those of 98 unaffected control individuals with respect to transforming growth factor alpha (TGFA) genotypes. Among the Caucasians in this population (83 CL/P, 84 controls), there was a significant difference in the restriction fragment length polymorphisms (RFLPs) observed after digestion with TaqI (x2 = 4.68, P = 0.03). The frequency of the C2 allele in the Caucasian CL/P population was 0.169, whereas that in the control group was 0.089. When the data for Caucasians, African‐Americans, and Asians were examined jointly, the x2 value for the pooled sample was 5.08 (P = 0.02). This confirms the hypothesis of Ardinger et al. [1989, Am J Hum Genet, 45:348–353] that TFGA itself or a closely linked gene contributes to the development of CL/P in humans. © 1993 Wiley‐Liss, Inc.
Common fragile site expression in lymphocytes from an individual mosaic for trisomy 8
Authors: Austin M. J. Finley , Neale Michael C. , Corey Linda A. , Nance Walter E. , Schieken Richard M. , Brown Judith A.
Published: June 2005

During the course of a survey of fragile site expression in lymphocytes from twins one member of a dizygotic pair was found to be mosaic for trisomy 8. One hundred fifty metaphases from this individual were analyzed (100 treated with aphidicolin and 50 untreated); 43% were 46,XY and 57% 46,XY, +8. No differences were observed between the treated and control cultures in either the proportions of normal and trisomic metaphases or the overall or specific fragile site expression in the normal and trisomic cells. © 1993 Wiley‐Liss, Inc.
Inversion (X)(p11.4q22) associated with Norrie disease in a four generation family
Authors: Pettenati Mark J. , Rao P. Nagesh , Weaver R. Grey , Thomas I. Tal , McMahan Mary Ruth
Published: June 2005

We report on a 4‐generation family in which Norrie disease occurs together with a pericentric inversion of the X chromosome in all affected males and carrier females. The breakpoint in the short arm of the X chromosome appears to be at the purported location of the Norrie disease gene. This is the second report of an association between Norrie disease and a chromosome aberration involving Xp11, and the first report of a specific gene disruption, thus physical gene location, due to a pericentric chromosome inversion. © 1993 Wiley‐Liss, Inc.
Premature aging and immunodeficiency: Mulvihill‐Smith syndrome?
Authors: Ohashi Hirofumi , Tsukahara Masato , Murano Ichiro , Fujita Kyoko , Matsuura Shinya , Fukushima Yoshimitsu , Kajii Tadashi
Published: June 2005

We report on a 30‐year‐old woman with premature aging, immunodeficiency, and other abnormalities. She had many manifestations of the Mulvihill‐Smith syndrome, a disorder that has been described in 4 sporadic individuals, ranging in age from 4 to 17 years. The common manifestations include short stature, microcephaly, a senile face with an under‐developed lower half, diminished facial subcutaneous fat, multiple pigmented nevi, sensorineural hearing loss, and a low IgG level. Our patient also had severe mental retardation, brachydactyly, severe T cell dysfunction, and suffered from severe verruca vulgaris and a chronic, active Epstein‐Barr virus infection. The fact that her parents were first cousins suggests autosomal recessive inheritance of her disorder. Two alternative possibilities were considered: the disorder in the patient represents the Mulvihill‐Smith syndrome with immune deficiency as a sign of its advanced stage, or a hitherto undescribed syndrome. © 1993 Wiley‐Liss, Inc.
Duplication 9q34→qter identified by chromosome painting
Authors: Spinner Nancy B. , Lucas Joe N. , Poggensee Marilyn , Jacquette Mary , Schneider Adele
Published: June 2005

We have studied an infant with multiple anomalies and a 46,XY,12p+ karyotype. Parental chromosomes were normal, and it was not possible to determine the identity of the extra material on chromosome 12 cytogenetically. Chromosome painting with probes from a chromosome 9 library identified this material as coming from chromosome 9, and cytogenetics established the duplication as 9q34→qter. Comparison of this patient with others reported with partial dup(9q) documented excellent concordance of minor anomalies, most notably dolichocephaly, “;deep‐set”; eyes, short horizontal palpebral fissures, beaked nose, micrognathia, arachnodactyly, and developmental delay. Identification of cytogenetically indeterminate abnormalities by molecular cytogenetics is very important, as it permits prognosis to be offered for families of newborn infants with unbalanced karyo‐types. © 1993 Wiley‐Liss, Inc.
Identical twins with Weissenbacher‐Zweymüller syndrome and neural tube defect
Authors: Ramer J. C. , Eggli K. , Rogan P. K. , Ladda R. L.
Published: June 2005

Neurologic abnormalities have been described only once previously in a child with Weissenbacher‐Zweymüller syndrome (WZS), a rare skeletal dysplasia, evident neonatally. We report on identical twin male infants with skeletal findings typical of WZS, including small size at birth, proximal limb shortness, mid face hypoplasia, and myopia. In addition, twin B had a parieto occipital encephalocele while twin A had a meningocele at the same location. Twin B has had significant delays in development and hearing loss. © 1993 Wiley‐Liss, Inc.
Interstitial deletion of 8q13.3→ 22.1 associated with craniosynostosis
Authors: Fryburg Julie S. , Golden Wendy L.
Published: June 2005

We report on a 3‐year‐old girl who has an interstitial deletion of chromosome 8q [46,XX, del(8)(q13.3q22.1)]. She has severe mental retardation and minor anomalies in addition to lambdoidal synostosis. This is the first report of craniosynostosis in association with this chromosomal deletion. The manifestations of our patient are compared to those of previously reported patients with similar deletions. © 1993 Wiley‐Liss, Inc.
Extrahepatic biliary atresia and associated anomalies: Etiologic heterogeneity suggested by distinctive patterns of associations
Authors: Carmi Rivka , Magee Carol A. , Neill Catherine A. , Karrer Frederick M.
Published: June 2005

Fifty‐one cases of extrahepatic biliary atresia (EHBA) with associated anomalies were found in a study of EHBA (251 cases). Analysis of segregation patterns of these anomalies in individual patients suggested the existence of 2 major groups: (1) 15 cases (29.4%) with various combinations of anomalies within the laterality sequence, and (2) 30 cases (58.8%) with one or 2 anomalies mostly involving the cardiac, gastrointestinal, and urinary systems. These latter anomalies did not follow any recognizable pattern. The third group of 6 cases all had intestinal malrotation, some with preduodenal portal vein; these cases show some similarity to the laterality sequence group and may represent a more confined phenotypic result of faulty situs determination.

This previously unattempted classification of patients with EHBA and associated anomalies might enable a more targeted approach towards identification of causes in this hetero‐geneous disorder. EHBA within the laterality sequence might prove a suitable candidate for a major gene mutation. Teratogenic, infectious and polygenic multifactorial causes might play a more significant role in EHBA associated with “nonsyndromic” organ system anomalies. © 1993 Wiley‐Liss, Inc.
18q‐mosaicism associated with Rett syndrome phenotype
Authors: Gordon Kevin , Siu Victoria Mok , Sergovich Fred , Jung Jack
Published: June 2005

Rett syndrome consists of a characteristic progressive encephalopthy in females. The cause of this syndrome is unknown. We present a patient with 18q‐mosaicism who, along with the characteristics of this autosomal deletion, also fulfills the clinical criteria for Rett syndrome. This may demonstrate heterogeneity within this as yet cinically defined syndrome. A thorough chromosomal analysis should be performed in suspected cases of Rett syndrome. © 1993 Wiley‐Liss, Inc.
Decrease in calcitonin‐containing cells in truncus arteriosus
Authors: Gamallo Carlos , García Marcial , Palacios José , Rodríguez José Ignacio
Published: June 2005

Experimental studies in chick embryos have demonstrated that truncus arteriosus (TA), a form of conotruncal cardiac defect, is due to abnormalities in the cranial neural crest. However, no data are available to support this hypothesis in humans with isolated TA. In the present study, the assessment of calcitonin immunoreactive cells (C‐cells) has been employed to evaluate whether or not the proportion of thyroid cells derived from the cranial neural crest is normal in patients with isolated TA. Thyroid sections from 15 such patients in which no other extracardiac malformations were neither clinically nor pathologically found, and from 11 control age‐matched patients were studied immunohistochemically at autopsy in order to determine the number and distribution of calcitonin‐containing cells. The volume density of C‐cells (0.888%) and the number of C‐cells per follicle (0.991) was significantly lower in patients with TA than in control patients (3.475%, and 2.367, respectively). The decrease of neural crestderived cells in the thyroid of patients with “isolated” TA documents more extent abnormalities than clinically suspected and supports the hypothesis of neural crest disturbance as the pathogenetic factor responsible for this heart malformation. © 1993 Wiley‐Liss, Inc.
Mutations in von Recklinghausen neurofibromatosis: An hypothesis
Authors: Zlotogora Joël
Published: June 2005

Von Recklinghausen neurofibromatosis or neurofibromatosis type I (NF1) is relatively frequent (1/3,000 livebirths) autosomal dominant condition. Some unusual aspects are noted in this disorder: new mutations are frequent and almost all are of paternal origin without parental age effect. The recurrence of NF1 among children of healthy parents is rare as opposed to other dominant disorders. I propose that in NF1 (1) new mutations occur often in somatic cells or in late germinal cells, however, they occur very rarely in early germinal cells leadding to germinal mosaicism and (2) the individual with somatic mosaicism presents symptoms of the disease. Therefore, an NF1 patient with an apparent new mutation is often a somatic mosaic for the mutation and if the mosaic is alo present in germinal cells some of his children will be affected. This hypotesis may explain the unusual aspects of mutation in NF1. © 1993 Wiley‐Liss, Inc.
Congenital scalp defects and vitreoretinal degeneration: Redefining the Knobloch syndrome
Authors: Seaver Laurie H. , Joffe Leonard , Spark Ronald P. , Smith Barbara L. , Hoyme H. Eugene
Published: June 2005

An apparently autosomal recessive syndrome of hereditary vitreoretinal degeneration (VRD) with retinal detachment, high myopia, and congenital encephalocele was described in 1971 by Knobloch and Layer [J Pediatr Ophthalmol 8:181–184]. Clinical confirmation of the presence of encephaloceles was lacking, and no neuropathologic studies were reported. We have evaluated a similarly affected family with 2 sibs with high myopia, VRD, and occipital scalp defects. Histologic examination of the scalp defects showed heterotopic neuronal tissue in both instances. The older girl has had a unilateral retinal detachment. Her other eye and both eyes of the younger sib have so far been treated successfully with prophylactic retinal cryotherapy. Both children have normal to above normal intelligence. The family reported by Knoblock and Lyer [1971] and the sibship herein described appear to represent a distinct autosomal recessive trait. Analysis of the associated defects suggests an underlying defect in early cephalic neuroectodermal morphogeneis. Data from these families imply that congenital occipital scalp defects rather than true encephaloceles may, as is true in some cases of Meckel syndrome, accompany Knobloch syndrome. The presence of a congenital midline scalp defect should alert the clinician to possible underlying central nervous system and/or ocular pathology and should lead to consideration of further diagnostic evaluations And prophylactic measures. © 1993 Wiley‐Liss, Inc.
New multisystemic disorder involving heart valves, skin, bones, and joints in two brothers
Authors: Borrone C. , Di Rocco M. , Crovato F. , Camera G. , Gambini C.
Published: June 2005

We report on 2 brothers with a severe progressive disorder characterized by thick skin, acne conglobata, “coarse” face, osteolysis, gingival hypertrophy, brachydactyly, camptodactyly, and mitral valve prolapse. The youngest brother died at age 24 years because of heart failure. Biochemical and pathological studies excluded known metabolic diseases.

We think that this is a new genetic disorder inherited in autosomal recessive or X‐linked recessive manner. © 1993 Wiley‐Liss, Inc.
In utero fetal muscle biopsy for the diagnosis of Duchenne muscular dystrophy in a female fetus “suddenly at risk”
Authors: Evans Mark I. , Farrell S. A. , Greb Anne , Ray Peter , Johnson Mark P. , Hoffman Eric P.
Published: June 2005

DNA methods to diagnose Duchenne muscular dystrophy (DMD) are not always informative, and we have published previously the first instance of in utero muscle biopsy to assess dystrophin in a male fetus having the same “X” as an affected sib. We present here a female fetus with a de novo X,1 translocation with breakpoint at Xp21, detected on amniocentesis for advanced maternal age. The translocation breakpoint placed her at high risk for DMD. In utero muscle biopsy at 20 weeks of gestation produced a specimen positive for dystrophin immunofluorescence indcating a likely normal fetus. The pregnancy was continued, and at term the baby girl was found to have normal serum creatine kinase levels, and was therefore unaffected with DMD. Our experiences add de novo Xp21 translocation to the indications for in uteromuscle biopsy for diagnosis of DMD. © 1993 Wiley‐Liss, Inc.
Possible second case of tricho‐oculo‐dermo‐vertebral (Alves) syndrome
Authors: Stratton Robert F. , Jorgenson Ronald J. , Krause Irene C.
Published: June 2005

We report on a 10‐year‐old girl with trichodysplasia, onychodysplasia, hyperpigmented ichthyoform lesions on her shins, mild enamel dysplasia, and hyperkeratosis involving the soles. This combination of ectodermal defects has only been described by Alves et al. [Am J Med Genet 10:213–218, 1981]. © 1993 Wiley‐Liss, Inc.
Case of (Y;1) familial translocation
Authors: Teyssier Michelle , Rafat Azim , Pugeat Michel
Published: June 2005

A balanced reciprocal translocation t(1;Y) (q11;q11) was found in an infertile man with severe oligoasthenospermia. The same translocation was found in his father. The role of X‐chromosome inactivation during meiosis in a male carrying a Y;autosome translocation is discussed. © 1993 Wiley‐Liss, Inc.
Alopecia universalis as a single abnormality in an inbred Pakistani kindred
Authors: Ahmad Mahmud , Abbas Hasan , Haque Sayedul
Published: June 2005

A Pakistani kindred comprising 5 generations contained 9 males and 4 females with alopecia universalis as a single abnormality without any associated defects. The skin biopsy from the scalp showed hair follicles without hair. Analysis of the pedigree is strongly suggestive of autosomal recessive inheritance, and consanguineous loops could account for all affected persons being homozygous for the abnormal allele. © 1993 Wiley‐Liss, Inc.
Study of isolated apparent amniogenic limb deficiency in Hungary, 1975–1984
Authors: Czeizel Andrew E. , Vitéz Márta , Kodaj Imre , Lenz Widukind
Published: June 2005

A population‐based and validated data set of 206 cases with apparent amniogenic limb deficiency was ascertained in Hungary between 1975 and 1984. Such limb defects frequently (36%) associated with nonlimb abnormalities. In 134 cases with isolated defects typically more limbs are affected, upper and lower limbs, right and left sides, and both sexes are equally affected. Case‐control analysis of such isolated cases indicates a lower socio‐economic status of parents, a higher parity, more frequent unwanted pregnancies, preterm birth, and a higher rate of threatened abortion. Familial occurrence was not found in 415 first‐degree relatives. © 1993 Wiley‐Liss, Inc.
Nonspecific immunity in down syndrome: A study of chemotaxis, phagocytosis, oxidative metabolism, and cell surface marker expression of polymorphonuclear cells
Authors: Novo Ernesto , García Miryam I. , Lavergne Julio
Published: June 2005

We have investigated several aspects of nonspecific immunity in Down syndrome (DS), utilizing peripheral polymorphonuclear leukocytes (PMNL), obtained from 12 children aged 8–16, diagnosed as trisomy 21, and their healthy matched controls. We used the under agarose method for chemotaxis assays, and flow cytometry for the determination of phagocytosis of monodispersed fluorescent beads, metabolic burst activity, and neutrophil surface marker expression on these cells.

Our results indicate that a chemotactic defect exists in PMNL of DS children. However, no statistically significant differences were found between PMNL from DS children and those from controls in phagocytosis, oxidative burst, and expression of the markers CD11a, CD11b, CD16, and CD 18.

Furthermore, no overexpression of CD11a and CD18 was present as a consequence of gene overdosage in PMNL from DS children. On the other hand, 3 different neutrophil sub‐populations could be observed according to the CD16 staining pattern in DS children and controls; this might be a consequence of genetic variation or may represent different states of activation of these cells. Other factors such as T‐cell involvement, and the role of cytokines, cyclic nucleotides, and zinc serum levels in DS patients should be further investigated in order to define the causes of the immunological derangement present in this condition. © 1993 Wiley‐Liss, Inc.
Pattern of cardiac malformation in oculoauriculovertebral spectrum
Authors: Kumar Anil , Friedman J. M. , Taylor Glenn P. , Patterson Michael W. H.
Published: June 2005

The reported prevalence of congenital heart defects (CHD) in the oculoauriculovertebral “spectrum” (OAVS) is 5–58%. This variability is mainly due to differences in the diagnostic criteria used, and to ascertainment bias introduced by selection of patients from different specialty databases. Two‐thirds of the cardiac anomalies reported are either tetralogy of Fallot (TOF) or ventricular septal defect (VSD). We found a CHD frequency of 19% in a series of 32 patients identified either through a genetic or autopsy database. The cardiac lesions were much more varied and complex than previously reported and included asplenia syndrome, ventricular inversion associated with double outlet right ventricle, pulmonary atresia with VSD, double outlet right ventricle, and infradiaphragmatic total anomalous pulmonary venous connection. Pulmonary and renal abnormalities were more common in OAVS patients with CHD than in those where the heart was normal. © 1993 Wiley‐Liss, Inc.
Interstitial deletion of chromosome 10, del(10) (q11.2q22.1) in a boy with developmental delay and multiple congenital anomalies
Authors: Zenger‐Hain Julie L. , Roberson Jacquelyn , Van Dyke Daniel L. , Weiss Lester
Published: June 2005

We describe a 4‐year‐old boy with an interstitial deletion of the long arm of chromosome 10:del(10) (q11.2q22.1). Frontal bossing, hypertelorism, bright blue iris color, up‐slanting palpebral fissures, a flat nasal bridge, a broad nose, apparently low‐set ears, micrognathia, deep philtrum, and hypotonia were noted neonatally. A murmur was noted at age 5½ months and surgical repair of subaortic stenosis was required at 4 years. At 4 years micrognathia was no longer evident, but the palate was high‐arched. The pattern of abnormalities included postnatal‐onset slow growth, short stature, mental retardation, and cardiac anomalies. © 1993 Wiley‐Liss, Inc.
E. coli sepsis as a presenting sign in neonatal propionic acidemia
Authors: Werlin Steven L.
Published: June 2005

An infant, who was later diagnosed with propionic acidemia presented with E. coli sepsis, a previously unreported association. © 1993 Wiley‐Liss, Inc.
Discrepancy in mosaic findings between chorionic villi and amniocytes: A diagnostic dilemma involving 45,X, 46,XY, and 47,XYY cell lines
Authors: Rubin Cathi H. , Williams John , Wang Boris B. T.
Published: June 2005

Discrepancies between cytogenetic findings in chorionic villi (CV) and fetal tissue have been reported. Several embryogenic models have been proposed to explain such discrepancies. We describe a case in which analysis of the direct preparation showed 24% 45,X and 76% 46,XY, with 43% 45,X and 57% 46,XY cells in cultured villi. Amniocentesis results disclosed 97% 46,XY and 3% 47,XYY. No 45,X cells were found in cultured amniocytes. These findings suggest that nondisjunction occurred early in postzygotic cleavage resulting in 3 cell lines. It is postulated that through selection, the less viable 45,X cells died out among those destined to become fetus proper but persisted among the cytotrophoblast and extraembryonic mesoderm cells. While there is probably selection against all aneuploid cell lines, 47,XYY cells are more likely to survive in the fetus. An explanation for the lack of 47,XYY cells in the CV might be simply that the tissue sampled was not representative of the cytogenetic make up of the entire placenta. © 1993 Wiley‐Liss, Inc.
Is Tourette syndrome a cause of sudden infant death syndrome and childhood obstructive sleep apnea?
Authors: Sverd Jeffrey , Montero Gerardo
Published: June 2005

The cause of sudden infant death syndrome (SIDS) is unknown. Sleep‐related impairment of respiratory control and arousal are postulated; hyperdopaminergic and hyposerotonergic dysfunction may contribute to events leading to infant apnea and SIDS. Psychosocial adversity and impulsive and compulsive behaviours characterize some families of SIDS victims. Tourette syndrome (TS) is a common hereditary neurobehavioral disorder characterized by the frequent presence of impulsive and compulsive behaviors. Sleep disorders are common and include sleep apnea and abnormal arousal. Hyperdopaminergic and hyposerotonergic abnormalities are postulated to contribute to the pathophyusiology of the disorder. The following is a report of the presence of incidents of infant apnea and SIDS in families in which TS was present. In an additional TS family, a child had obstructive sleep apnea syndrome (OSAS). Results of a preliminary survey suggest that TS gene carriers are at increased risk of life‐threatening apneas of infancy and that the prevalence of SIDS in such families may be 2 to 5 times the prevalence in the general population. The presence in some pedigrees of sleep apnea in children and adults suggest that in some instances disorders of sleep‐related ventilatory control and arousal occurring throughout the life‐span share common pathophysiological mechanisms. © 1993 Wiley‐Liss, Inc.
Hematologic abnormalities in children with down syndrome
Authors: Roizen Nancy J. , Amarose Anthony P.
Published: June 2005

We compared the hematologis parameters of 18 otherwise healthy children with Down syndrome (DS) in the age range of 2–6 years to those of 18 healthy non‐DS controls matched for age and gender. The children with DS had MCVs and hematocrits increased significantly compared to controls and decreased WBCs compared to controls; 66% of the children with DS compared to 11% of non‐DS controls had MCVs greater than the 97th percentile for age (P <0.0001); the mean MCVs were 86.9 and 80.6, respectively. Although hematocrits were within normal limits for age for all DS and non‐DS subjects, the DS patients had significantly higher hematocrits (39.1% vs. 36.9%, P <0.014). We also found that 33% of the children had WBCs <5% for age compared to 6% of controls. To determine whether folate deficiency contributed to these observations, we measured serum and RBC folate concentrations: these were not significantly different between the 2 groups. We conclude that macrocytosis and leukopenia are common in children with DS. © 1993 Wiley‐Liss, Inc.
Incontinentia pigmenti achromians (hypomelanosis of ITO, MIM 146150): Further evidence of localization at Xp11
Authors: Koiffmann Célia P. , de Souza Deise H. , Diament Aron , Ventura Heloisa B. , Alves Rosana S. , Kihara Sonia , Wajntal Anita
Published: June 2005

We report on a girl with apparent hypomelanosis of Ito(ITO); cytogenetic studies disclosed the karyotype 46,X,t(X;10)(p11;q11)mat. We present further evidence that at least one of the genetic forms of ITO is located at Xp11; reviewing the clinical characteristics of patients with incontinentia pigmenti type 1 (IP1) and ITO with X‐autosome translocations, we suggest that IP1 and ITO represent allelic forms or a contiguous gene syndrome. Thus, different genetic alterations in this region (Xp11) give rise to ITO or IP1 or borderline phenotypes. We also suggest that all patients with ITO, due to Xp11 mutation, have functional or genetic mosaicisms. © 1993 Wiley‐Liss, Inc.
Mild mandibulofacial dysostosis in a child with a deletion of 3p
Authors: Arn Pamela Hawks , Mankinen Carl , Jabs Ethylin W.
Published: June 2005

We report on a patient with mild mandibulofacial dysostosis and a small interstitial deletion of 3p,46,XY,del(3)(p23p24.12). Linkage of Treacher Collins syndrome, the most common of the mandibulofacial dysostosis, to the 5q31.3→q33.3 region of chromosome 5 has been established. This is the fourth report of a patient with mandibulofacial dysostosis with a chromosome abnormality outside the 5q31.3 area. Mandibulofacial dysostosis is a heterogeneous entity, and evaluation and counseling of affected individuals should be undertaken with caution. © 1993 Wiley‐Liss, Inc.