bluuebunny/crossref_metadata_2025_split huggingface dataset:
Johnson–McMillin syndrome, a neuroectodermal syndrome with conductive hearing loss and microtia: Report of a new case
Authors: Schweitzer Daniela N. , Yano Shoji , Earl Dawn L. , Graham John M. 
Published: June 2003

AbstractIn 1983, Johnson et al. described 16 related individuals with alopecia, anosmia or hyposmia, conductive hearing loss, microtia and/or atresia of the external auditory canal, and hypogonadotrophic hypogonadism inherited in an autosomal dominant pattern. Other less constant manifestations included facial asymmetry, mental retardation, congenital heart defect, cleft palate, and choanal stenosis. An isolated case was reported later (Johnston et al. [1987: Am J Med Genet 26: 925–927]) and thereafter an affected mother and son (Hennekam and Holtus [1993: Am J Med Genet 47: 714–716]). We describe an additional unrelated female patient with features resembling those of the previously reported cases. She presented with intrauterine growth deficiency, microcephaly, alopecia, bilateral microtia with canal atresia, conductive hearing loss, partial left facial palsy, posterior cleft palate, left choanal stenosis, tetralogy of Fallot, developmental delay, and right thumb polydactyly. Because the phenotypic abnormalities in this syndrome affect the brain, facial structures, ectoderm and its derivatives, outflow tract of the heart, and Rathke's pouch derivatives, this has suggested to previous authors etiologic involvement of the ectoderm and neuroectoderm of the first and second branchial arches, Rathke's pouch, and the diencephalon. Microtia with conductive hearing loss differentiates the condition from other ectodermal dysplasias. In the initial report, females appeared somewhat less affected than males, and there was male‐to‐male transmission. The mother of our patient manifests subtle features, which suggest she may be a mildly affected female. Additionally, there is a family history of early‐onset alopecia in the maternal grandfather's relatives. © 2003 Wiley‐Liss, Inc.
Vestibular dysfunction in adult patients with osteogenesis imperfecta
Authors: Kuurila K. , Kentala E. , Karjalainen S. , Pynnönen S. , Kovero O. , Kaitila I. , Grénman R. , Waltimo J. 
Published: June 2003

AbstractProgressive hearing loss is a major symptom in osteogenesis imperfecta (OI), a genetic brittle bone disease. Vertigo is frequently associated with otosclerosis in which the hearing loss clinically resembles that in OI. Vertigo is also common in basilar impression (BI) found in up to 25% of adult OI patients. In order to evaluate the cause, frequency, and characteristics of vertigo in OI, 42 patients were studied by interview, clinical examination, and audiological examination supplemented with electronystagmography (ENG) and lateral skull radiography. Audiometry showed hearing loss in 25 patients (59.5%). Nine patients (21%) displayed abnormal skull base anatomy in the forms of basilar impression, basilar invagination, or both, all designated here as BI. Twenty‐two patients (52.4%) reported vertigo, mostly of floating or rotational sensation of short duration. Patients with hearing loss tended to have more vertigo than patients with normal hearing. Vertigo was not correlated with type of hearing loss or auditory brain‐stem response (ABR) pathology. ENG was abnormal in 14 patients (33.3%). No dependency was found between vertigo and deviant ENG results. Patients with BI tended to have more vertigo than patients with normal skull base but the difference was not statistically significant. Neither ENG pathology, nor the presence or type of hearing loss showed correlation with BI. In conclusion, vertigo is common in patients with OI. In most cases, it may be secondary to inner ear pathology, and in only some patients does BI explain it. Since some OI patients without BI or hearing loss also suffer from vertigo, further clinical and neurological studies are needed to define the pathogenesis of vertigo in OI. © 2003 Wiley‐Liss, Inc.
A novel mutation of keratin 9 in epidermolytic palmoplantar keratoderma combined with knuckle pads
Authors: Lu Yong , Guo Chenhong , Liu Qiji , Zhang Xiyu , Cheng Lin , Li Jiangxia , Chen Bingxi , Gao Guimin , Zhou Haibin , Guo Yishou , Li Yefu , Gong Yaoqin 
Published: June 2003

AbstractEpidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominantly inherited disease. We studied a family from Shandong, China, having patients suffering from EPPK with a unique symptom—knuckle pads. We noticed that both the hyperkeratosis and knuckle pads in the Chinese family were friction‐related. Candidate gene analysis was carried out using linkage analysis and direct sequencing. A novel L160F mutation in keratin 9 was found, and its effects on the secondary structure of keratin 9 were studied. We predict that the L160F mutation is also responsible for the knuckle pads in the family. Our study provides a new clue for the study of the function of keratin 9. © 2003 Wiley‐Liss, Inc.
A newly recognized autosomal recessive syndrome with abnormal vertebral ossification, rib abnormalities, and nephrogenic rests
Authors: Prefumo Federico , Homfray Tessa , Jeffrey Iona , Moore Isabella , Thilaganathan Baskaran 
Published: June 2003

AbstractWe describe three cases of a severe malformation syndrome in siblings of both sexes. The characteristic features observed were absent intrauterine ossification of an apparently normal cartilaginous spinal column; rib abnormalities, with unossified segments and posterior gaps; thoracic hypoplasia; and multiple intralobar nephrogenic rests in the kidneys. This syndrome can be identified in early pregnancy by ultrasound scans due to the lack of ossification of the thoraco‐lumbar spine and its association with increased nuchal translucency thickness. We suggest that this is a newly recognized autosomal recessive syndrome. © 2003 Wiley‐Liss, Inc.
Growth retardation, developmental delay, distinctive face, multiple endocrine abnormalities, and adenylyl cyclase dysfunction: A new syndrome?
Authors: Salerno M. , Amabile G. , Mandato C. , Di Maio S. , Lecora M. , Avvedimento E.V. , Andria G. 
Published: June 2003

AbstractWe report on a 17‐year‐old male with severe pre‐ and postnatal growth retardation, craniosynostosis, distinctive facial features, acanthosis nigricans, deafness, mental retardation and progressive multi‐organ involvement, particularly of the endocrine system, including hypothyroidism, hypogonadism, transitory hypoparathyroidism, and insulin resistance. In order to find a common mechanism explaining these multiple abnormalities, we searched for a possible defect in the signal transduction pathways from membrane to nucleus involving G‐protein coupled receptors (GPCR). Adenylyl cyclase activity was evaluated by assaying c‐AMP in the patient's cultured fibroblasts stimulated with several drugs and toxins acting on different effectors upstream of adenylyl cyclase. The preliminary results indicate a reduced cAMP accumulation in the patient, neither caused by constitutive activation of Gi nor inhibition of Gs signaling, and probably resulting from an alteration in the adenylyl cyclase system. The differential diagnosis with syndromes showing common clinical features with our patient is discussed. © 2003 Wiley‐Liss, Inc.
Perinatal‐lethal Gaucher disease
Authors: Mignot C. , Gelot A. , Bessières B. , Daffos F. , Voyer M. , Menez F. , Fallet Bianco C. , Odent S. , Le Duff D. , Loget P. , Fargier P. , Costil J. , Josset P. , Roume J. , Vanier MT. , Maire I. , Billette de Villemeur T. 
Published: June 2003

AbstractGaucher disease is a lysosomal storage disease caused by glucocerebrosidase deficiency. Although purely visceral in most cases, some Gaucher disease patients have neurological signs. Signs of Gaucher disease appear after a symptom‐free period, except in rare cases with fetal onset. The description of such cases was based mainly on single reports and siblings. We report here a series of perinatal‐lethal Gaucher disease cases highlighting the specificity of this phenotype. We retrospectively studied eight original cases of proven Gaucher disease with fetal onset. Non‐immune hydrops fetalis was present in all cases but one, and associated with hepatosplenomegaly, ichthyosis, arthrogryposis, and facial dysmorphy. The similarities between our cases and 33 previously described cases allow us to better delineate the perinatal‐lethal Gaucher disease phenotype. Hydrops fetalis, in utero fetal death and neonatal distress are prominent features. When hydrops is absent, neurological involvement begins in the first week and leads to death within three months. Hepatosplenomegaly is a major sign, and associated with ichthyosis, arthrogryposis, and facial dysmorphy in some 35–43% of cases. Perinatal‐lethal Gaucher disease is a specific entity defined by its particular course and signs that are absent in classical type 2 Gaucher disease. Our study provides clues to the diagnosis of this likely underdiagnosed condition, which must be biochemically confirmed in order to propose appropriate genetic counselling. © 2003 Wiley‐Liss, Inc.
Upper airway malformation associated with partial trisomy 11q
Authors: Zhao Hui‐quan , Rope Alan F. , Saal Howard M. , Blough‐Pfau Ruthann I. , Hopkin Robert J. 
Published: June 2003

Abstract11q trisomy is associated with a recognizable pattern of multiple malformations. Review of the literature reveals the following recurrent themes common to complex and isolated 11q trisomy: mental retardation, pre‐ and postnatal growth retardation, hypotonia, a distinct pattern of facial features, congenital heart defects, and limb malformations. We report four patients with partial trisomy 11q, none of which arose from the common 11/22 translocation. Three of the four patients had the previously unreported finding of upper airway obstruction secondary to a malformed epiglottis. The critical region for this malformation appears to be 11q21‐23.2. © 2003 Wiley‐Liss, Inc.
Wisconsin syndrome in a patient with interstitial deletion of the long arm of chromosome 3: Further delineation of the phenotype
Authors: Ko Wai‐tai , Lam Wai‐fan , Lo Fai‐man , Chan Wing‐kwong , Lam Tak‐sum 
Published: June 2003

AbstractInterstitial deletions of the long arm of chromosome 3 are uncommon. Most cases are related to the blepharophimosis–ptosis–epicanthus inversus syndrome (BPES), which is mapped to 3q23. We report on a case with a de novo chromosomal deletion of 3q23 and 3q25. We review the literature on the reported cases of 3q deletion and find that the condition of our patient is not typical of the BPES. Rather, she shares similarity to a patient with Wisconsin syndrome, first discovered in 1976. © 2003 Wiley‐Liss, Inc.
Prevalence of trisomy 21 following folic acid food fortification
Authors: Ray Joel G. , Meier Chris , Vermeulen Marian J. , Cole David E.C. , Wyatt Philip R. 
Published: June 2003

AbstractPolymorphisms of maternal genes responsible for normal folate metabolism may be associated with an increased risk of fetal trisomy 21. By January 1998, most of Canada's flour was being fortified with folic acid. We investigated whether the prevalence of antenatally and postnatally detected trisomy 21 changed before and after folic acid food fortification. A total of 218,977 women underwent second trimester maternal serum screening for trisomy 21 in the 48 months before fortification and 117,986 women were screened in the 29 months after fortification. There were 375 identified cases of trisomy 21 before fortification (1.71 per 1,000), compared to 201 cases thereafter (1.70 per 1,000) for a crude prevalence ratio (PR) of 0.99 (95% confidence interval [CI] 0.84–1.18). The associated risk of trisomy 21 did not change after adjustment for mean maternal age (adjusted PR 0.99 [95% CI 0.82–1.19]). Similarly, no significant decline in the monthly prevalence of trisomy 21 was observed using autoregressive integrated moving average time series analysis (P = 0.24). In conclusion, we failed to observe a decline in the occurrence of trisomy 21 following folic acid food fortification. © 2003 Wiley‐Liss, Inc.
Medical geneticists' duty to warn at‐risk relatives for genetic disease
Authors: Falk Marni J. , Dugan R. Beth , O'Riordan Mary Ann , Matthews Anne L. , Robin Nathaniel H. 
Published: June 2003

AbstractA patient who refuses to notify their relatives of potential at‐risk status brings a genetics provider to face conflicting ethical principles and ill‐defined legal precedent. Genetics professionals' views on the disclosure of patient information to at‐risk relatives have remained largely unexamined. Prior analyses have been limited to identifying factors contributing to genetics providers' self‐predicted responses in hypothetical scenarios. Our group was the first to examine the clinical experience of genetic counselors with this issue [Dugan et al., 2003]. We report here results from our follow‐up survey of medical geneticists who are members of either the American Society of Human Genetics and/or American College of Medical Genetics in an effort to identify their experiences in warning at‐risk relatives and the factors driving their decision‐making processes. Over two‐thirds of medical geneticists surveyed (69%, 143/206) believe they do bear responsibility to warn their patients' relatives when found to be at‐risk for genetic disease. One‐quarter (25%, 31/123) of medical geneticists who faced the dilemma of a patient refusing to notify their at‐risk relatives seriously considered disclosure to those at‐risk relatives without patient consent. Only four respondents proceeded to warn at‐risk relatives of their status. Whereas genetic counselors cited emotional issues as playing a primary role in their decision not to warn, medical geneticists identified patient confidentiality, eventual case resolution by other means, and legal liability as the major factors leading to non‐disclosure in 76% of actual scenarios. Responsibilities of medical geneticists, genetic counselors, and non‐genetics healthcare professionals facing this issue will need to be more clearly defined to provide optimal medical care within the bounds of acceptable practice. © 2003 Wiley‐Liss, Inc.
Ring 21 chromosome and a satellited 1p in the same patient: Novel origin for an ectopic NOR
Authors: Ki Anita , Rauen Katherine A. , Black Lauri D. , Kostiner Dana R. , Sandberg Per L. , Pinkel Daniel , Albertson Donna G. , Norton Mary E. , Cotter Philip D. 
Published: June 2003

AbstractNucleolus organizer regions (NORs) are present on the satellite stalks located on the short arms of the acrocentric chromosomes. NORs present on non‐acrocentric chromosomes (ectopic NORs) are rare and were reported in both phenotypically normal and abnormal individuals. We describe a patient, ascertained prenatally, with an ectopic NOR on 1p and a ring 21 chromosomes. Amniocentesis was performed at 27‐weeks gestation on a 19‐year‐old woman after identification of intrauterine growth retardation (IUGR) by ultrasound. Cytogenetic analysis of amniocytes from the fetus showed a mos 46,XX,1ps,r(21) (p11.2q22.3)[44]/45,XX,1ps,‐21[6] karyotype. Parental karyotypes were normal, indicating a de novo origin for these rearrangements in the fetus. Molecular cytogenetic characterization of the 1ps showed no loss of euchromatin and retention of the telomeric repeats. Characterization of the r(21) using array comparative genomic hybridization (CGH) identified that the deletion was approximately 5 Mb encompassing most of chromosome band 21q22.3. The ectopic NOR (1ps) was most likely derived from the acentric 21p fragment generated by the chromosome breakage event that lead to formation of the r(21) chromosome. This represents a novel mechanism for the origin of ectopic NORs. In addition, this study illustrates the importance of FISH analysis with telomeric and subtelomeric probes for characterization of chromosomes with ectopic NORs. © 2003 Wiley‐Liss, Inc.
Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP‐5‐IgG
Authors: Cross Shelley A. , Salomao Diva R. , Parisi Joseph E. , Kryzer Thomas J. , Bradley Elizabeth A. , Mines Jonathan A. , Lam Byron L. , Lennon Vanda A. 
Published: June 2003

AbstractAutoantibodies have defined two paraneoplastic visual disorders related to small‐cell lung carcinoma: retinopathy (“CAR”‐IgG [23kDa, recoverin]) and optic neuritis collapsin response‐mediated protein 5 (CRMP‐5‐IgG [62kDa]). Among 16 patients with CRMP‐5‐IgG and optic neuritis (aged 52–74 years; all smokers, 9 women), we documented coexisting retinitis in 5. None had CAR‐IgG. Fifteen had subacute vision loss, swollen optic discs, and field defects. Vascular leakage was evident at and remote from the disc; 5/5 tested had abnormal electroretinograms. Nine had striking vitreous cells. Vitrectomy showed reactive lymphocytosis (4/4), predominantly CD4+ (1/1). Most patients had multifocal neurological accompaniments. Cerebrospinal fluid contained lymphocytes (7‐32), elevated protein, multiple oligoclonal immunoglobulin bands, and CRMP‐5‐IgG. Three patients superficially resembled Devic's disease at presentation. One autopsied patient had predominantly CD8+ T lymphocytes infiltrating optic nerve and spinal cord. Eleven patients had confirmed small‐cell carcinoma; 1 had imaging evidence of lung cancer; 3 had renal or thyroid carcinoma. Full‐length CRMP‐5 protein was identified in normal retina and optic nerve by Western blot analyses. Photoreceptor cells, retinal ganglion cells, and nerve fibers exhibited CRMP‐5–specific immunoreactivity. In summary, CRMP‐5‐IgG defines a paraneoplastic ophthalmological entity of combined optic neuritis and retinitis with vitreous inflammatory cells. Positive serology obviates the need for vitreous biopsy and expedites the search for cancer. Ann Neurol 2003
Nonsyndromic mental retardation and cryptogenic epilepsy in women with Doublecortin gene mutations
Authors: Guerrini Renzo , Moro Francesca , Andermann Eva , Hughes Elaine , D'Agostino Daniela , Carrozzo Romeo , Bernasconi Andrea , Flinter Frances , Parmeggiani Lucio , Volzone Anna , Parrini Elena , Mei Davide , Jarosz Jozef M. , Morris Robin G. , Pratt Polly , Tortorella Gaetano , Dubeau François , Andermann Frederick , Dobyns William B. , Das Soma 
Published: June 2003

AbstractDCX mutations cause mental retardation in male subjects with lissencephalypachygyria and in female subjects with subcortical band heterotopia (SBH). We observed four families in which carrier women had normal brain magnetic resonance imaging (MRI) and mild mental retardation, with or without epilepsy. Affected male subjects had SBH or pachygyria‐SBH. In two families, the phenotype was mild in both genders. In the first family, we found a tyr138his mutation that is predicted to result in abnormal folding in the small hinge region. In the second family, we found an arg178cys mutation at the initial portion of R2, in the putative β‐sheet structure. Carrier female subjects with normal MRI showed no somatic mosaicism or altered X‐inactivation in lymphocytes, suggesting a correlation between mild mutations and phenotypes. In the two other families, with severely affected boys, we found arg76ser and arg56gly mutations within the R1 region that are predicted to affect DCX folding, severely modifying its activity. Both carrier mothers showed skewed X‐inactivation, possibly explaining their mild phenotypes. Missense DCX mutations may manifest as non‐syndromic mental retardation with cryptogenic epilepsy in female subjects and SBH in boys. Mutation analysis in mothers of affected children is mandatory, even when brain MRI is normal. Ann Neurol 2003
Immature cortex lesions alter retinotopic maps and interhemispheric connections
Authors: Restrepo C. Ernesto , Manger Paul R. , Spenger Christian , Innocenti Giorgio M. 
Published: June 2003

AbstractUnilateral lesions of the occipital visual areas performed on postnatal day 5 (P5) in the ferret are not compensated by the appearance, in the lesioned hemisphere, of visual responses at ectopic locations. Instead, when parts of the visual areas are spared, they show abnormal retinotopic organizations; furthermore, callosal connections are abnormally distributed in relation to the retinotopic maps. Lesions that completely eliminate the visual areas including the posterior parietal cortex cause the appearance of abnormal callosal connections from the primary somatosensory cortex on the lesion side to the contralateral, intact, posterior parietal cortex. The occipital visual areas (17, 18, 19, and 21) of the intact hemisphere show a normal retinotopy but lose callosal connections in territories homotopic to the lesions. These findings clarify the nature and limits of structural developmental plasticity in the visual cortex. Early in life, certain regions of cortex have been irreversibly allocated to the visual areas, but two properties defining the areas, that is, retinotopy and connections, remain modifiable. The findings might be relevant for understanding the consequences of early‐onset visual cortical lesions in humans. Ann Neurol 2003
Antiepileptic drug use in nursing home admissions
Authors: Garrard Judith , Harms Susan , Hardie Nancy , Eberly Lynn E. , Nitz Nicole , Bland Patricia , Gross Cynthia R. , Leppik Ilo E. 
Published: June 2003

AbstractAlthough 1 of 10 nursing home residents is taking an antiepileptic drug (AED), no study to our knowledge has determined whether most residents are already receiving AED treatment when they are admitted or are given these drugs afterward. That differentiation was the focus of this study. The study group consisted of 10,318 residents, 65 years and older, admitted to 510 nursing homes located throughout the United States during the first quarter of 1999. AED prevalence at admission was 7.7%; three fifths had an epilepsy/seizure indication. In a multivariate analysis, factors associated with AED use at admission included epilepsy/seizure, bipolar depression, age group, and cognitive performance. In the follow‐up cohort (N = 9,516), postadmission initiation of AEDs was 2.7%; one fifth had an epilepsy/seizure indication. In the multivariate analysis, factors associated with postadmission AED initiation included epilepsy/seizure indication, bipolar depression, age group, peripheral vascular disease, and cognitive performance. This rate of AED postadmission initiation within the first 3 months of admission was much higher than expected, suggesting that new symptoms may develop after admission. Results also show that the rate of AED use in nursing homes is not static. Ann Neurol 2003;54:000–000
Oxidative capacity correlates with muscle mutation load in mitochondrial myopathy
Authors: Jeppesen Tina D. , Schwartz Marianne , Olsen David B. , Vissing John 
Published: June 2003

AbstractThe purpose of this study was to investigate the correlation between the level of mutated mitochondrial DNA in muscle and oxidative capacity in 24 patients with mitochondrial myopathy (MM). Maximal oxygen uptake (VO2max), workload (Wmax), and venous plasma lactate levels were measured during an incremental cycle test to exhaustion in 17 patients with point mutations of mtDNA and in seven with single, large‐scale deletions of mtDNA (chronic progressive external ophthalmoplegia [CPEO]). Results were compared with those in 25 healthy matched subjects. The mutation load in MM patients was 67 ± 5% (range, 29 – 99%). VO2max and Wmax correlated with percentage of heteroplasmy (r > 0.82; p < 0.005) and were lower in patients versus healthy subjects (p < 0.000005). Exercise‐induced peak increases in heart rate, ventilation, and resting plasma lactate levels correlated with muscle mutation load (r > 0.71; p < 0.005). Exercise‐induced increases in plasma lactate correlated with muscle mutation load in CPEO patients (r = 0.95; p < 0.005). Impaired oxidative capacity and ragged red muscle fibers were found in CPEO and 3243A→G patients with mutation loads as low as 45 and 57%, respectively. The study indicates that oxidative capacity correlates directly with skeletal muscle mutation load in MM patients, and that the mutation threshold level for impaired oxidative metabolism in MM patients is lower than found in in vitro studies. Ann Neurol 2003