bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carrier detection of the fragile X syndrome with flanking RFLP markers and linkage analysis
Authors: Väisänen Marja‐Leena , Kähkönen Marketta , Leisti Jaakko 
Published: June 2005

AbstractLinkage analysis was performed in 34 fragile X (fra[X]) families in order to study the efficiency of carrier detection using the restriction fragment length polymorphisms (RFLPs) closely linked to fra(X) locus (FRAXA).The marker loci used were F9, DXS105, DXS98, DXS369, DXS297 and DXS477 proximally and DXS465, DXS296, DXS304, DXS52 and F8C distally to FRAXA. Flanking heterozygosity was achieved in 60% of the females with a combination of 3 restriction enzymes and 6 closest RFLP markers. When adding more distant markers and other restriction enzymes to the analysis, the proportion of females heterozygous for flanking polymorphisms increased to 96%. With RFLP‐analysis most (85/91) females at high risk of being a carrier could be separated clearly into 2 groups: those with a very low and those with a very high risk. The 6 cases with a recombination between flanking markers did not benefit from RFLP‐analysis.
Validation of linkage‐based DNA‐diagnosis of fragile X gene carriers with the CGG repeat probe
Authors: Van Oost Bernard A. , Smits Arie P. T. , Dreesen Jos C. F. M. , van den Ouweland Ans M. W. , Oostra Ben A. 
Published: June 2005

AbstractWe have evaluated our carrier testing for the fragile X [fra(X)] syndrome, which was based on linked DNA markers, with the direct analysis of the CGG repeat sequence in the fra(X) gene. PstI and EcoRI blots were hybridized with a probe derived from the region just 3′ of the CGG repeat in Xq27.3. We found the mutation analysis to be very sensitive as all 71 obligate gene carriers as well as 135 fra(X) patients tested showed evidence for an increased restriction fragment length encompassing the CGG repeat sequence with or without dispersion of the hybridization signal (mosaicism). Based on linked DNA markers, 6 out of 50 cytogenetic negative and mentally normal males at risk and 15 of 72 females at risk had inherited the allele at risk. All of these diagnoses could be confirmed by analysis of the CGG repeat length.
New York State screening program for fragile X syndrome: A progress report
Authors: Nolin Sarah L. , Snider Donald A. , Jenkins Edmund C. , Dobkin Carl S. , Patchell Kathleen , Krawczun Michael , Strong Gloria , Colwell Maryanne , Victor Arnold , Payyapilli Thomas , Turczyn Marianne , Little Anne , Nagaraja U. , Doyle Nancy , Kenefick Barbara , Sullivan Connie 
Published: June 2005

AbstractNew York State has established a program to screen post‐pubertal mentally retarded males for the fragile X [fra(X)] syndrome. The goal of the program is to identify affected males and inform their families of the diagnosis. Females in these families who are at risk for inheriting the mutation will then be able to determine their carrier status and consider that information in making reproductive decisions.Males were evaluated for 10 features of the syndrome by physicians and nurses throughout the state; cytogenetic analysis was carried out on a subset of this population. A total of 1332 males has been screened and chromosome studies have been completed for 489. Forty‐three (9%) were positive for fra(X), and an additional 11 other chromosome abnormalities were identified. The 43 patients belonged to 38 families. Of the 24 families who were informed of the diagnosis, 12 consulted genetic counseling centers for follow‐up studies and 12 did not.
Notes on the population genetics of fragile X syndrome
Authors: Vianna‐Morgante Angela M. , Otto P. A. 
Published: June 2005

AbstractOur analysis of fragile X‐inactivation in normal and mentally retarded heterozygotes led us to conclude that a fraction of female carriers of the imprinted (fully mutated) allele is phenotypically normal as a consequence of X‐inactivation. Taking this into accout, we derived equilibrium equations for the fragile X [fra(X)] genotype frequencies. We also showed that small variations in the value of s (selection coefficient of affected heterozygotes) and r (imprinting rate during oogenesis) affect genotype ratios significantly.
High prevalence of the Fra(X) syndrome cannot be explained by a high mutation rate
Authors: Smits Arie , Smeets Dominique , Hamel Ben , Dreesen Jos , van Oost Bernard 
Published: June 2005

AbstractThe overall prevalence of the fragile X [fra(X)] mutation, as determined by population studies, is approximately 1 in 850 [Gustavson et al., 1986; Webb et al., 1986]. This prevalence suggests a very high mutation rate which, in turn, suggests that many patients have to represent sporadic cases. In order to obtain an accurate estimate of the proportion of sporadic cases, we performed genealogic, cytogenetic and DNA linkage studies as well as direct analysis of the CGG repeat in relatives of 84 fra(X) probands. We did not find any evidence for the presence of sporadic cases. In 11 probands consanguinity could be proven by the detection of common ancestors, in 5 related families up to 9 generations ago. In the other 6 related families the mutation could be traced back 4‐6 generations. In 3 or more generation families we were able to demonstrate that half of the probands carried the grandpaternal fra(X) gene. These results imply that rather than a high mutation rate, both Normal Transmitting Males (NTM's) and mentally normal female carriers contribute considerably to the high prevalence of the fra(X) syndrome.
Penetrance estimate of the Fra(X) gene using pointer versus direct estimate
Authors: de Haan A. F. J. , Smits A. P. T. , Smeets D. F. C. M. , van Oost B. A. 
Published: June 2005

AbstractDirect estimate of the penetrance of the fra(X) gene was compared with the estimate using the Pointer computer program. Direct estimate gave overall penetrances of 85% for male and 64% for female carriers. The estimates calculated by the Pointer program were 82% for males and 38% for females. It is argued that the use of the Pointer program gives incorrect estimates of the penetrance of the fra(X) gene.
Simpson‐golabi‐behmel syndrome associated with renal dysplasia and embryonal tumor: Localization of the gene to Xqcen‐q21
Authors: Hughes‐Benzie Rhiannon M. , Hunter Alasdair G. W. , Allanson Judith E. , Mackenzie Alex E. 
Published: June 2005

AbstractWe report 6 affected males in a 5‐generation family with X‐linked Simpson‐Golabi‐Behmel (SGB) syndrome. All had pre‐ and postnatal overgrowth with 2 adult males attaining heights over 195 cm. Other features included “coarse” face with hypertelorism, broad nasal root, cleft palate, full lips with a midline groove of the lower lip, grooved tongue with tongue tie, prominent mandible, congenital heart defects, arrhythmias, supernumerary nipples, splenomegaly, large dysplastic kidneys, cryptorchidism, hypospadias, skeletal abnormalities and postaxial hexadactyly. All affected individuals were of normal intelligence. One boy died at age 19 months of a neuroblastoma.The putative origin of the gene in this family was the maternal great grandmother of the propositus. Eight carrier females, who showed varying manifestations of the gene, have been identified.Anthropometric analysis has identified preliminary characteristic craniofacial dimensions in this syndrome. Molecular studies have shown a maximal lod score of 2.81 with no recombinants observed for the SGB‐DXYS68 pairing, mapping the disorder to Xqcen‐Xq21.3.
MRX8: An X‐linked mental retardation condition with linkage to Xq21
Authors: Schwartz Charles E. , May Melanie , Huang Tim , Ledbetter David , Anderson Gail , Barker David F. , Lubs Hebert A. , Arena Fernando , Stevenson Roger E. 
Published: June 2005

AbstractA family in which 6 males have X‐linked mental retardation has been studied with polymorphic DNA probes. The males differ from unaffected males only in impaired intellect and in smaller head size. The gene that causes mental retardation in the family appears to be located in band Xq21 on the basis of linkage with 3 markers: DXS250, DXS345 and DXS3 (θmax = 0.00; Zmax = 1.6). A multipoint lod score of 2.36 was obtain with no recombination relative to DXS326 in Xq21. This family is considered to have nonspecific X‐linked mental retardation and has been given the designation MRX8.
Neuropsychological studies in families with fragile‐X negative X‐linked mental retardation
Authors: Cianchetti Carlo , Sannio‐Fancello Giuseppina , Fratta Anna‐Lisa , Pischedda Maria‐Paola , Spinicci Gabriella , Marrosu Maria‐Giovanna , Filippi Giorgio 
Published: June 2005

AbstractNeuropsychological studies were performed in 82 subjects of 12 families with X‐linked, fragile X negative, mental retardation (MR). Subjects were examined with Wechsler tests (WPPSI, WISC‐R or WAIS, according to their capabilities), Progressive Matrices, Bender or Santucci and memory tests.Physical findings in 5 families were characterised by micro‐orchidism (MiO), microcephaly (MiC), short stature (SS) and non‐specific facial features (XMR±MiO±MiC±SS). The 11 males with MR had a very low IQ, ranging from 13 to 37 (mean 21.2±8.8); this did not constitute a profile definition. Among the females of their families, 4 had subnormal or borderline IQ, respectively 74, 66, 38 and 37.A second group (2 families) had MiO but with normal stature and occipito‐frontal circumference (XMR±MiO). The 7 males with MR had an IQ ranging from 24 to 43 (mean 35.1±5.8) and showed frequently better results in performance than in verbal subtests. In these 2 families, 5 females had subnormal or borderline IQ, respectively 77, 72, 71, 70 and 20.In the 5 families of the third group, XMR±MaO(fraX‐), several affected males had macro‐orchidism (MaO) and facial changes similar to those of fragile X syndrome. IQ variability, also in the same family (e.g.: the 3 brothers of family 3 had, respectively, an IQ of 26, 28 and 68; the 2 brothers of family 1 had an IQ of 13 and 63) and different profiles. Two females were severely affected (IQ 16 and 24), while another 4 had an IQ, respectively, of 63, 69, 71 and 72.
Hypothalamic‐pituitary‐gonadal function in two infants with Smith‐Lemli‐Opitz syndrome
Authors: Pankau Rainer , Partsch Carl‐Joachim , Funda Johannes , Sippell Wolfgang Günther 
Published: June 2005

AbstractWe report on the hypothalamic‐pituitary‐gonadal function in 2 male infants with the Smith‐Lemli‐Opitz (SLO or RSH) syndrome. Both infants had abnormal external genitalia. Basal and LHRH stimulated plasma gonadotropins were normal for age (1 month). Plasma testosterone, androstenedione, and dehydroepiandrosterone sulfate were normal for age and sex. Some forms of congenital adrenal hyperplasia (17,20‐desmolase deficiency, 17α‐hydroxylase deficiency, and 3β‐hydroxysteroid dehydrogenase deficiency) were ruled out by hormonal studies. The endocrinological findings indicate a normal hypothalamic‐pituitary‐gonadal function and a normal adrenal steroid biosynthesis in these 2 patients. A partial androgen receptor defect causing the genital malformations seems possible in one patient. Whether 5α‐reductase deficiency is the cause of the male pseudohermaphroditism in SLO syndrome remains the subject of future studies. © 1992 Wiley‐Liss, Inc.
Skeletal dysplasia, intracerebral calcifications, optic atrophy, hearing impairment, and mental retardation: Nosology of dysosteosclerosis
Authors: Chitayat David , Silver Keneth , Azouz E. Michel 
Published: June 2005

AbstractA girl who presented at 3 months of life with severe developmental delay, blindness, and hearing impairment was found to have intracerebral calcifications. Skeletal films showed craniotubular bone modeling consistent with dysosteosclerosis. The nosology of this disorder is discussed. © 1992 Wiley‐Liss, Inc.
Restrictive dermopathy, a lethal form of arthrogryposis multiplex with skin and bone dysplasias: Three new cases and review of the literature
Authors: Verloes Alain , Mulliez Nicole , Gonzales Marie , Laloux Françoise , Hermanns‐Lě Trinh , Piérard Gérald E. , Koulischer Lucien 
Published: June 2005

AbstractRestrictive dermopathy is a rare, lethal autosomal recessive syndrome. We report on 3 unrelated affected stillborn infants of consanguineous parents. Clinical findings include a tight, thin, translucent, taut skin, which tears spontaneously in flexion creases, arthrogryposis multiplex congenita (including the temporomandibular joint), enlarged fontanelles, typical face and dysplasia of clavicles and long bones. Histologic abnormalities include hyperplastic, abnormally keratinized epidermis, reduced tonofilaments, thin, compact dermis with hypoplasia of the elastic fibres, and abnormal subcutaneous fat. Fifteen previous cases are reviewed. © 1992 Wiley‐Liss, Inc.
Autosomal dominant polycystic kidney disease: New information for genetic counselling
Authors: Bear John C. , Parfrey Patrick S. , Morgan Janet M. , Martin Christopher J. , Cramer Benvon C. 
Published: June 2005

AbstractWe evaluated the accuracy of ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) and factors influencing its prognosis in members of 17 Newfoundland families originally described in 1984. In 10 families showing genetic linkage between ADPKD and markers for the PKD1 locus, rates of false negative ultrasonographic diagnosis are estimated as 36% below the age of 10 years and 8% or less thereafter, comparable with findings of genetic linkage studies of a subset of family members. At ages above 30 years, false negative ultrasonographic diagnosis of PKD1 disease is unlikely. In 2 families in which PKD1 disease is unlikely. In 2 families in which ADPKD is not coinherited with PKD1 markers, only 11% of members aged less than 30 years had kidney cysts. The mean (SE) age of onset of ESRD is 56.3 (1.8) years for persons with the PKD1 form of ADPKD, and 68.7 (1.7) years for affected members of families in which ADPKD is not co‐inherited with PKD1 markers (P = 0.01). In the PKD1 families, age of onset of end stage renal disease (ESRD) was unrelated to the sex of the affected individual but was earlier in persons inheriting the disease from their mothers than from their fathers (50.5 vs. 64.8 years, P = 0.004), consistent with an influence of genetic imprinting on disease progresion. In females with a PKD1 mutation, onset of ESRD was not influenced by parity. In PKD1 families, resemblance in age of onset of ESRD was apparent; variation was less within than between families (F = 13.0, P < 0.0001), and risk of false negative ultrasonographic diagnosis appears largely restricted to families in which ESRD occurs relatively late. © 1992 Wiley‐Liss, Inc.
Molecular genetic and immunological analysis of dystrophin of a young patient with X‐linked muscular dystrophy
Authors: Ikeya Kiyoko , Saito Kayoko , Hayashi Kensuke , Tanaka Hikaru , Hagiwara Yasuko , Yoshida Mikiharu , Yamauchi Akemi , Fukuyama Yukio , Ishiguro Tsuneo , Eguchi Chikahiko , Ozawa Eijiro 
Published: June 2005

AbstractWe examined the nucleotide sequence of deleted part of dystrophin mRNA and its translational product with immunoblot and immunohistochemical methods in a 6‐year‐old boy with a deleted DMD/BMD gene. On Southern blot analysis of his genomic DNA, we found a deletion of exons 10 to 37 in the DMD/BMD gene, which was expected to preserve the translational open reading frame (ORF). Dystrophin mRNA from his biopsy sample was amplified by polymerase chain reaction (PCR) and sequenced. The mRNA lacked the sequence corresponding to the gene from exons 10–37, and the translational ORF was preserved. The transcript was expected to code a 260 kDa protein. Dystrophin expressed in this patient was investigated with immunological methods. A 260 kDa protein was detected by immunoblot analysis with antidystrophin antiserum against nondeleted regions. These observations confirmed the preservation of the reading frame and the 260 kDa protein was produced as a mutant dystrophin. All these are compatible with the diagnosis of BMD. However, the immunohistochemical pattern of his muscle cells was peculiar. With deleted‐region‐directed antiserum, the membrane was not stained at all as in DMD patients. In contrast, with nondeleted‐region‐directed antiserum, all the muscle cell membrane was stained continuously as in non‐DMD/BMD individuals. These are quite different from the staining pattern in most BMD patients where muscles are stained patchily or discontinuously. © 1992 Wiley‐Liss, Inc.
Recurrence of extrahepatic biliary atresia in two half sibs
Authors: Gunasekaran Thirumazhisai S. , Hassall Eric G. , Steinbrecher Urs P. , Yong Siu‐Li 
Published: June 2005

AbstractExtrahepatic biliary atresia (EHBA) usually is a sporadic disorder. Familial cases, including occurrence in sibs and twins, have been reported. We report the first recurrence of EHBA in two half sibs born to a common father and unrelated mothers and suggest the possibility of gonadal mosaicism for a new dominant mutation. © 1992 Wiley‐Liss, Inc.
Neu‐Laxova syndrome: Prenatal ultrasonographic diagnosis, clinical and pathological studies, and new manifestations
Authors: Shapiro Israel , Borochowitz Zvi , Degani Shimon , Dar Hanna , Ibschitz Izu , Sharf Mordechai 
Published: June 2005

AbstractA diagnosis of the Neu‐Laxova syndrome (NLS) was made by ultrasonography at 32 wks of gestation. Ultrasonographic examination showed intrauterine growth retardation (IUGR), Dandy‐Walker anomaly, choroid plexus cysts, receding forehead and microcephaly, bilateral cataract without prominent eyes, scalp edema with no generalized edema, retrognathia, curved penis, and flexion deformities of limbs.The findings in this case are consistent with NLS; however, they did not fit any of Curry's [1982] groups. Massive swelling of hands and feet were among the main manifestations in classic NLS cases. In the case presented herein, edema was noted only in the scalp. This might shed further light on the question of variability vs. heterogeneity in the NLS.This case shows the existing possibility of an early diagnosis of NLS and adds Dandy‐Walker anomaly and choroid plexus cysts as new findings to this syndrome. © 1992 Wiley‐Liss, Inc.
Additional case of neuhäuser megalocornea and mental retardation syndrome with congenital hypotonia
Authors: Santolaya Jose M. , Grijalbo Alfonso , Delgado Alfonso , Erdozaín Gabriel 
Published: June 2005

AbstractWe report on a 3‐1/2‐year‐old Spanish girl with the Neuhäuser megalocornea and mental retardation syndrome. A review shows that megalocornea, mental retardation, and, presumably, hypotonia, are the major manifestations for diagnosis. The facial appearance of the typical cases is characterised by frontal bossing, broad nasal bridge, mild hypertelorism, long upper lip, and small mandible. © 1992 Wiley‐Liss, Inc.
Apparent cleidocranial dysplasia associated with abnormalities of 8q22 in three individuals
Authors: Brueton Louise A. , Reeve Ann , Ellis Richard , Husband Peter , Thompson Elizabeth M. , Kingston Helen M. 
Published: June 2005

AbstractCleidocranial dysplasia is an autosomal dominant, generalised skeletal disorder characterised by variable clavicular hypoplasia, frontal bossing, multiple Wormian bones, and delayed eruption of the teeth. The gene locus for this syndrome has not yet been assigned. Three individuals with manifestations of cleidocranial dysplasia associated with rearrangements of chromosome 8q22 are described. The evidence presented suggests that the gene for cleidocranial dysplasia may be located on chromosome 8q in humans in a region showing homology to mouse chromosome 3. © 1992 Wiley‐Liss, Inc.
Pallister‐Hall syndrome associated with an unbalanced chromosome translocation
Authors: Kuller Jeffrey A. , Cox Victoria A. , Schonberg Steven A. , Golabi Mahin 
Published: June 2005

AbstractWe report 3 cases of Pallister‐Hall syndrome involving hypothalamic hamartoblastoma, hypopituitarism, cranial, and limb abnormalities. The first 2 cases represent the first apparent sibs reported with this syndrome. Patient 1 represents the first known patient with this syndrome with an abnormal karyotype.
Hypothesis: Jadassohn nevus phakomatosis: A paracrinopathy with variable phenotype
Authors: Kousseff Boris G. 
Published: June 2005

AbstractIt has been postulated that the phakomatoses are paracrine growth regulation disorders (paracrinopathies). To determine how Jadassohn nevus phakomatosis (JNP) may fit such a pathogenetic model, a phenotype analysis of 13 propositi with JNP and a review of most reported JNP patients were done. The phenotypes of the propositi and the reviewed patients showed a great variability from a solitary congenital epidermal nevus to extensive cutaneous lesions with associated severe noncutaneous anomafies. Review of long‐term observations of JNP patients demonstrated considerable phenotypic changes within and beyond the boundaries of the nevi. The changes included a multitude of postnatal rare benign and/or malignant tumors and unusual manifestations: renal rickets, hepatomegaly, visceral cysts, vasculopathy, and even gangrene. Thus, a life‐long predisposition to dysregulation of paracrine growth factors (GFs, regulatory peptides, peptide regulatory factors, and cytokines), foremost somatomedin‐C (Sm‐C, IGF‐I), epidermal, fibroblast, platelet‐derived GFs, and transforming GF‐β is implied. Laboratory evidence for the presumed GF dysregulation in the phakomatoses came from tissue culture study of patients with neuro‐fibromatosis type 1 (NF‐1). Compared to controls their “normal” skin showed ultrastructural changes of markedly increased number of melanin macroglobuli within the melanocytes. Paracrine GFs as relevant to hamartomatous growth were incriminated by radioimmunoassays of cutaneous neurofibromas showing two‐fold or greater increase of Sm‐C levels compared to the levels in the adjacent skin. Thus, NF‐1 appears to be a paracrinopathy. JNP shows many more dynamic changes throughout the life span of the patients than NF‐1. In the near future paracrinology may aid endocrinology and oncology in treating patients with disorders of these three growth mechanisms in man. © 1992 Wiley‐Liss, Inc.
Encephalocraniocutaneous lipomatosis and the Proteus syndrome: Distinct entities with overlapping manifestations
Authors: McCall Sherman , Ramzy Magda I. , Cure Joel K. , Pai G. S. 
Published: June 2005

AbstractWe have studied three children with cutaneous (epidermal nevi), subcutaneous (lipomas, plantar skin thikening), vascular (hemangioma, lymphangioma), skeletal (osteoma, exostosis, localized hypertrophy), and neurological (hydrocephaly, lissencephaly, partial agenesis of the corpus callosum) developmental defects associated with the Proteus syndrome and related hamartoneoplastic conditions. We compared our findings in these three patients with those of 50 others with Proteus syndrome and nine with encephalocraniocutaneous lipomatosis (ECCL) reported in the literature. We found that Proteus syndrome and ECCL have distinct identities even though some clinical manifestations are shared by both and a few patients have manifestations of both conditions. © 1992 Wiley‐Liss, Inc.
New multiple congenital anomalies: Mental retardation syndrome (MCA/MR) with facio‐cutaneous‐skeletal involvement
Authors: Borochowitz Zvi , Pavone Lorenzo , Mazor Galia , Rizzo Renata , Dar Hanna 
Published: June 2005

AbstractFive unrelated patients (a male and 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which has been designated the facio‐cutaneous‐skeletal (FCS) syndrome and which includes mental retardation with specific sociable, humorous behavior, characteristic facial appearance, excessive generalized skin, postnatal growth failure, and skeletal involvement. Consanguinity was noted in 2 patients, thus autosomal recessive inheritance is suggested. © 1992 Wiley‐Liss, Inc.