Association of autism in two patients with hereditary multiple exostoses caused by novel deletion mutations of EXT1.
Department of Pediatrics, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi, Tochigi 329-0498, Japan.
Two boys from separate families presented with hereditary multiple exostoses (EXT) and autism associated with mental retardation. Their fathers both expressed a clinical phenotype of hereditary multiple exostoses milder than those of the patients and without the associated mental disorder. The EXT1 and EXT2 genes from lymphocytes of the affected individuals were analyzed by using denaturing high-performance liquid chromatography and direct sequencing. A novel deletion mutation, 1742delTGT-G in exon 9 of EXT1, causing a frameshift was detected in one boy and his father. Another novel deletion mutation, 2093delTT in exon 11 of EXT1, causing transcription termination was detected in the other affected boy and his father. EXT1 is expressed in the brain, and both EXT1 and EXT2 proteins are associated with glycosyltransferase activities required for the biosynthesis of heparan sulfate, which also has activity in the brain. The coincidental association of mental disorders in the boys was not completely excluded. However, these results suggest the involvement of EXT1 in the development of mental disorders, including mental retardation and autism.
PLoS One. 2012 ;7 (1):e29734 22253766
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Multiple Osteochondromas (MO; previously known as multiple hereditary exostosis) is an autosomal dominant genetic condition that is characterized by the formation of cartilaginous bone tumours (osteochondromas) at multiple sites in the skeleton, secondary bursa formation and impingement of nerves, tendons and vessels, bone curving, and short stature. MO is also known to be associated with arthritis, general pain, scarring and occasional malignant transformation of osteochondroma into secondary peripheral chondrosarcoma. MO patients present additional complains but the relevance of those in relation to the syndromal background needs validation. Mutations in two enzymes that are required during heparan sulphate synthesis (EXT1 or EXT2) are known to cause MO. Previously, we have used zebrafish which harbour mutations in ext2 as a model for MO and shown that ext2⁻/⁻ fish have skeletal defects that resemble those seen in osteochondromas. Here we analyse dental defects present in ext2⁻/⁻ fish. Histological analysis reveals that ext2⁻/⁻ fish have very severe defects associated with the formation and the morphology of teeth. At 5 days post fertilization 100% of ext2⁻/⁻ fish have a single tooth at the end of the 5(th) pharyngeal arch, whereas wild-type fish develop three teeth, located in the middle of the pharyngeal arch. ext2⁻/⁻ teeth have abnormal morphology (they were shorter and thicker than in the WT) and patchy ossification at the tooth base. Deformities such as split crowns and enamel lesions were found in 20% of ext2⁺/⁻ adults. The tooth morphology in ext2⁻/⁻ was partially rescued by FGF8 administered locally (bead implants). Our findings from zebrafish model were validated in a dental survey that was conducted with assistance of the MHE Research Foundation. The presence of the malformed and/or displaced teeth with abnormal enamel was declared by half of the respondents indicating that MO might indeed be also associated with dental problems.
Division of Pediatric Hematology-Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7236, USA. firstname.lastname@example.org
BACKGROUND The causes of autistic disorders (AD) are not known. Abnormalities of tumor suppressor genes have suggested that these genes may be important to the development of autism in some cases, and result in an increased risk of developing cancer or other neoplasms. We explore possible associations between AD and childhood cancer. PROCEDURE We reviewed our institutional pediatric cancer database for all new cancer diagnoses 1997-2007. Medical records from patients older than 2 years at last visit were reviewed for a diagnosis of AD. The prevalence of AD was estimated for neoplasms overall and for specific tumor types, and compared with that in the general pediatric population. RESULTS Of 702 eligible patients, 7 (1%; 95% CI:(0.4%, 2.04%)) were labeled as AD, not different than the prevalence of AD in North Carolina's general population (0.65%, P = 0.35). Cancer diagnoses for these 7 children were acute lymphoblastic leukemia (n = 1), acute nonlymphocytic leukemia (n = 2), non-Hodgkin lymphoma (n = 1), Hodgkin Disease (n = 1), brain tumor (n = 1), osteogenic sarcoma (n = 1). CONCLUSIONS These data do not suggest that there is a high concordance between AD and childhood cancer. However, studies of large rigorously characterized AD cohorts will be needed to definitively address this issue.
Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, India. email@example.com
BACKGROUND Hereditary multiple exostosis (HME) is an autosomal dominant bone disorder, characterized by short stature and the presence of multiple benign tumors mainly at the ends of long bones. HME is genetically heterogeneous with two known genes on 8q24 (EXT1) and 11p11 (EXT2), and a third minor locus mapped to 19p (EXT3). The majority of EXT1 and EXT2 mutations result in premature protein truncation and loss of function. MATERIALS AND METHODS We analyzed two autosomal dominant HME families of Indian origin. Linkage analysis using fluorescently labeled microsatellite markers at the candidate gene regions was performed. Mutation analysis was carried out by bidirectional sequencing of purified PCR products. RESULTS We found linkage in one family to EXT1 and in the other family to EXT2. Mutation screening in the EXT1 gene revealed a novel frameshift mutation, a single base deletion in exon 1 (c.142delC). This mutation segregated in all affected members and was absent in the unaffected family members and 60 unrelated controls. In the second family, a previously unreported stop mutation, the substitution c.817C>T, was observed in the EXT2 gene in all affected members and in none of the unaffected family members and 90 unrelated controls. CONCLUSIONS Our findings expand the mutation spectrum of EXT1 and EXT2 and highlight the genetic and phenotypic heterogeneity of HME.
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Brain Dev. 2011 Apr 28;: 21531096
Another promising treatment option for neuroblastoma-associated opsoclonus-myoclonus syndrome by oral high-dose dexamethasone pulse: Lymphocyte markers as disease activity.
Makiko Oguma, Akira Morimoto, Akiko Takada, Yoshifumi Kashii, Tokiko Fukuda, Masato Mori, Takanori Yamagata, Hideo Sugie, Mariko Y Momoi
Department of Pediatrics, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
A one-year-old boy with neuroblastoma (NBoma)-associated opsoclonus-myoclonus syndrome (OMS) was treated by oral high-dose dexamethasone (DEX) pulses (20mg/m(2)/day of DEX for three consecutive days) every 28days for 6months after resection of the tumor. All OMS symptoms improved after the first course of DEX pulse therapy and disappeared after the last course. No adverse effects were observed. Minor deterioration of his developmental quotient was noted 33months after the onset of the disease. NBoma remission has been maintained since treatment. Before DEX pulse therapy, frequency of T lymphocyte, in particular CD4-positive cell decreased markedly resulted in low CD4/8 ratio in the peripheral blood (PB). The frequency of B lymphocyte increased, especially in cerebrospinal fluid. These aberrant values in PB were reversed by DEX pulse therapy and correlated well with the neurological symptoms. A prospective study that assesses the efficacy of this promising and inexpensive treatment for OMS is warranted.
Unilaterally and rapidly progressing white matter lesion and elevated cytokines in a patient with Tay-Sachs disease.
Tomomi Hayase, Jun Shimizu, Tamako Goto, Yasuyuki Nozaki, Masato Mori, Naoto Takahashi, Eiji Namba, Takanori Yamagata, Mariko Y Momoi
Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
We report the case of a girl with Tay-Sachs disease who had convulsions and deteriorated rapidly after an upper respiratory infection at the age of 11 months. At the age of 16 months, her seizures became intractable and magnetic resonance imaging of the brain showed high signal intensity on T2-weighted images and marked swelling in the white matter and basal nucelei of the right hemisphere. Her seizures and right hemisphere lesion improved with glycerol and dexamethasone treatment. When dexamethasone was discontinued, her symptoms worsened and lesions later appeared in the left hemisphere. Her cerebrospinal fluid showed elevated levels of the cytokines TNF-alpha and IL-5. It is considered that inflammation contributes to disease progression in Tay-Sachs disease.
Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
Linkage analysis has reported the chromosomal region 7q21 to be related with autism. This region contains an imprinting region with MECP2-binding sites, and DLX5 is reported to be modulated by MECP2. DLX5 and adjacent DLX6 are homeobox genes working in neurogenesis. From these points, DLX5 and DLX6 are candidate genes for autism. Therefore, we analyzed the expression of DLX5 and DLX6, and also PEG10 as a control in the lymphoblasts of autistic spectrum disorder (ASD) patients by real-time PCR to identify potential abnormality of expression. And we also analyzed DLX5 and DLX6 on ASD patients for mutation by direct sequence. The expression level of DLX5 was not different between ASD and controls but was higher in four ASD patients compared to controls. Clinical features of these four patients were variable. DLX5 expression was biallelic in two ASD patients and two controls, indicating that DLX5 was not imprinted. There was no mutation in DLX5 in ASD. Although DLX5 was not likely to play major role in ASD, genes relating to DLX5 expression and downstream of DLX5 are considered to be candidate genes for some of the ASD patients. In DLX6, we detected a G656A base change (R219H) in two ASD patients who were male siblings. DLX6 may contribute to the pathogenesis of ASD.
Department of Pediatrics, Jichi University, Shimotsuke, Tochigi. firstname.lastname@example.org
A 7-year-old girl was diagnosed with generalized myasthenia gravis and became steroid-dependent. Dose of prednisolone could not be reduced to < 2 mg/kg/day on alternate days, despite adverse effects. Thymectomy was avoided. Oral tacrolimus was initiated at 1.0 - 1.3 mg/kg/day. Ptosis and weakness of the lingual and pharyngeal muscles began to ameliorate 2 weeks later, and disappeared within 2 months. Serum titer of anti-acetylcholine receptor antibody also declined. During the subsequent two years, remission was maintained although prednisolone was reduced to half the original dose. No adverse effects of tacrolimus were noted. This case suggests the usefulness of tacrolimus in the treatment of childhood myasthenia gravis.
Yuko Otake, Takanori Yamagata, Yasuko Morimoto, Mari Imi, Masato Mori, Toshinori Aihara, Takashi Ichiyama, Mariko Y Momoi
Department of Pediatrics, Jichi Medical University, 3311-1 Yaksiji, Shimotsuke, Tochigi, Japan.
The patient was an 11-month-old boy who developed encephalopathy associated with respiratory syncytial virus bronchiolitis. Right hemispheric encephalopathy was indicated by left hemiparesis and a diffuse right hemispheric lesion detected with magnetic resonance imaging. Elevated levels of interleukin-6 in the cerebrospinal fluid during the acute phase suggested the involvement of increased production of one or more cytokines in the pathogenesis of viral related encephalopathy, similarly to that proposed for influenza encephalopathy.
Hideo Yamanouchi, Naoko Kawaguchi, Masato Mori, George Imataka, Takanori Yamagata, Teisuke Hashimoto, Mariko Y Momoi, Mitsuoki Eguchi, Masashi Mizuguchi
Department of Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan. email@example.com
To establish a novel subtype of acute infantile encephalopathy, the clinical and radiologic features of nine infants with acute encephalopathy involving the bilateral frontal lobes were examined. These patients had convulsive status epilepticus with hyperpyrexia followed by a prolonged impairment of consciousness for 2-20 days. After the recovery of consciousness, all the patients manifested regression of verbal function and lack of spontaneity. Some of them also exhibited stereotypic movements, instability of mood, or catalepsy. Transient postictal edema in both frontal lobes was suggested by diffusion-weighted magnetic resonance imaging. Attenuated cerebral perfusion in the frontal lobes was demonstrated by single-photon emission computed tomography at the tenth day after onset or subsequently. Serial studies disclosed atrophic changes in the frontal lobes. All patients manifested regression or retardation of motor and verbal functions. The recovery of intellectual deficit was slower and less prominent than that of motor dysfunction. These unique features suggest that the frontal lobes are the focus of this novel subtype of acute encephalopathy, which we propose to call acute infantile encephalopathy predominantly affecting the frontal lobes.
Two new XPD patients compound heterozygous for the same mutation demonstrate diverse clinical features.
Mitsuo Fujimoto, Suzanne N Leech, Therina Theron, Masato Mori, Heather Fawcett, Elena Botta, Yasuyuki Nozaki, Takanori Yamagata, Shin-Ichi Moriwaki, Miria Stefanini, Mariko Y Momoi, Hidemi Nakagawa, Sam Shuster, Celia Moss, Alan R Lehmann
Department of Dermatology, Jichi Medical School, Japan.
Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are both rare autosomal recessive disorders with defects in DNA repair. They are usually distinct both clinically and genetically but in rare cases, patients exhibit the clinical characteristics of both diseases concurrently. We report two new phenotypically distinct cases of XP with additional features of CS (xeroderma pigmentosum and Cockayne syndrome crossover syndrome (XP/CS)) carrying an identical mutation (G47R) in the XPD gene within the N terminus of the protein. Both patients had clinical features of XP and CS but only one fulfilled most criteria for diagnosing CS. Unusually, patient 1 developed early skin cancer, in contrast to patient 2, who never developed any malignancies. Cells from both these patients have repair defects typical of xeroderma pigmentosum complementation group D (XPD) cells, but also had the phenotype of uncontrolled DNA breakage found specifically in XPD/CS cells and similarly reduced levels of TFIIH. Despite these similarities between our two patients, their clinical features are quite different and the clinical severity correlates with other cellular responses to ultraviolet irradiation.
Department of Pediatrics, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Tochigi 329-0498, Japan.
Methyl-CpG binding protein 2 gene (MECP2), the gene implicated in Rett syndrome, was also reported to be involved in mental retardation and autism. MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a nuclear protein family sharing the methyl-CpG binding domain (MBD) and are related to transcriptional repression. In 65 Japanese autistic patients, all the exons of each gene were screened for mutations by DHPLC, and the results were confirmed by direct sequencing. An R269C mutation that resulted in the addition of cysteine near a cysteine rich region was found in the MBD1 gene in one patient. This mutation was also detected in the patient's father with some phenotypes of autism and his normal sister, but not in 151 controls. Two repeat length polymorphisms,(GGGGCC)2 to 3 and (GGC)4 to 5, were detected in MBD2, and several polymorphisms were detected in each gene. Although our findings could not confirm that the genes of this family are responsible for the etiology in the majority of autistic patients, the R269C mutation in the MBD1 gene may relate to autism. The potential association of the high-polymorphic gene variants with autism needs to be studied further. Furthermore, these polymorphisms are useful for linkage analysis.
Department of Pediatrics, Jichi Medical School, 33311-1 Yakushiji, Minamikawachi, Tochigi 329-0498, Japan.
Early-onset ataxia with oculomotor apraxia and hypoalbuminemia is an autosomal recessive cerebellar ataxia characterized by oculomotor apraxia, peripheral neuropathy, and hypoalbuminemia. Mutations in aprataxin gene located at chromosome 9q13 have been identified recently in Japanese and European patients. This study reports two cases of siblings with early-onset ataxia with oculomotor apraxia and hypoalbuminemia, which manifested early onset before 2 years of age with relatively rapid progression and severe dystonia. Both of the siblings were compound heterozygotes with aprataxin gene mutations, 689 insT and G692A, in exon 5 that encodes the histidine triad domain of the aprataxin protein. The novel missense mutation, G692A, was not present in 40 unrelated and unaffected individuals.
Absence of causative mutations and presence of autism-related allele in FOXP2 in Japanese autistic patients.
Department of Pediatrics, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi, Tochigi 329-0498, Japan.
We analyzed the FOXP2 gene, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, for a possible causative mutation in autism. FOXP2 was reported to be mutated in patients with a severe speech and language disorder. FOXP2 was located on chromosome 7q31, which is one of the loci involved in autism. Autism and specific language impairment share some of their clinical phenotypes. In addition, FOXP2 was expressed abundantly in the brain. We screened all of the exons of FOXP2 for causative mutations in 53 Japanese autistic patients using denaturing high-performance liquid chromatography and direct sequencing. A delCAA in exon 5 causing one glutamine deletion in the first polyglutamine tract was detected in four patients and in 2 of 50 control individuals. The frequency of the TT allele with the G to T base change in intron 15 was significantly high in the autistic population. The other base changes included one silent base change (A569G) in exon 5 and three in introns. Our results may suggest a relationship between autism and the FOXP2 gene or a gene located nearby.
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Tiling resolution array-CGH shows that somatic mosaic deletion of the EXT gene is causative in EXT gene mutation negative multiple osteochondromas patients.
Károly Szuhai, Ivy Jennes, Danielle de Jong, Judith V M G Bovée, Malgorzata Wiweger, Wim Wuyts, Pancras C W Hogendoorn
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands. firstname.lastname@example.org
Multiple osteochondromas (MO) is a hereditary skeletal disorder characterized by the presence of cartilage capped bony outgrowths at bone surface. Causative mutations in EXT1 or EXT2 genes have been described in 85-90 % of MO cases. However, in about 10-15 % of the MO cases, genomic alterations can not be detected, implying the potential role of other alterations. We have designed a custom-made Agilent oligonucleotide-based microarray, containing 44,000 probes, with tiling coverage of EXT1/2 genes and addition of 68 genes involved in heparan sulfate biosynthesis and other related pathways. Out of the 17 patient samples with previously undetected mutations, a low level of deletion of the EXT1 gene in about 10-15% of the blood cells was detected in two patients and mosaic deletion of the EXT2 was detected in one patient. Here we show that for the first time somatic mosaicism with large genomic deletions as the underlying mechanism in MO formation was identified. We propose that the existence of mosaic mutations and not alterations of other heparan sulfate biosynthesis related genes play a significant role in the development of MO in patients who are tested negative for mutations in Exostosins.
Greenwood Genetic Center, Greenwood, South Carolina 29418, USA. email@example.com
Myotonia congenita is a nondystrophic muscle disorder characterized by muscle stiffness and muscle hypertrophy. The disorder can be inherited in an autosomal-dominant (Thomsen disease) or autosomal-recessive (Becker disease) manner. Both forms of myotonia congenita are attributable to mutations in the CLCN1 gene. Treatment with a variety of medications has led to long-term improvement in the clinical course of affected individuals. We describe a Honduran boy with myotonia congenita and a novel p.L287I mutation in the CLCN1 gene. The patient's unaffected father carries the same mutation, most likely reflecting autosomal-recessive myotonia congenita, with an inability to find a second mutation. The patient received carbamazepine treatment for 1 year, resulting in decreased muscle stiffness, increased strength, and improved quality of life in school and with peers.
Dermatol Online J. 2010 ;16 (1):11 20137753
Ana Filipa Duarte, Alberto Mota, Teresa Baudrier, Paulo Morais, António Santos, Rita Cerqueira, Purificação Tavares, Filomena Azevedo
Department of Dermatology, Hospital de São João, EPE, Porto, Portugal. firstname.lastname@example.org.
Piebaldism is a rare disorder present at birth and inherited as an autosomal dominant trait. It results from a mutation in the c-kit proto-oncogene and is associated with a defect in the migration and differentiation of melanoblasts from the neural crest. Clinical manifestations and phenotypic severity strongly correlates with the site of mutation within the KIT gene. Here we report a 3-year-old boy and his 33-year-old father with leukoderma and poliosis associated with clinical criteria for Neurofibromatosis type 1. Genetic study of both revealed a p.Gly610Asp mutation in the KIT gene. This familiar mutation has not yet been reported in the literature. There are rare reports of piebaldism in association with neurofibromatosis type I.
Institute of Psychophysiology and Rehabilitation, Kaunas University of Medicine, Palanga, Lithuania. email@example.com
PURPOSE OF REVIEW Thyroid hormones play important roles in brain development and function. Recent findings concerning thyroid hormones secretion, transport, and metabolism in the brain have provided a better understanding of the role of thyroid hormones in mental disorders. RECENT FINDINGS The intracellular actions of thyroid hormones in brain are determined by a complex of factors, including circulating concentrations of thyroid hormones, availability of free hormone, activity of thyroid hormone transporters and deiodinase enzymes, and activity of thyroid hormone receptors. Individual genetic variations and mutations of thyroid-axis-related proteins influence thyroid hormone activity in the brain and contribute to the presentation of mental disorders, as well as to response to psychiatric treatments. SUMMARY Consideration of molecular mechanism related to genetic alterations in thyroid hormone transport into the neuron, intracellular thyroid hormone metabolism in the brain, as well as polymorphism in thyroid hormone receptors, opens new venues for better understanding of thyroid hormone effects in the brain as well as for finding genetic markers and new targets for the treatment of mental disorders.
Genet Mol Res. 2009 ;8 (1):173-178 19283684
A novel COL1A1 gene-splicing mutation (c.1875+1G>C) in a Brazilian patient with osteogenesis imperfecta.
C Barbirato, M G Almeida, M Milanez, V Sipolatti, M R G O Rebouças, A N Akel Jr, V R R Nunes, A M S Perrone, M Zatz, I D Louro, F Paula
Departamento de Ciências Biológicas, Núcleo de Genética Humana e Molecular, Centro de Ciências Humanas e Naturais, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
Osteogenesis imperfecta is a heterogeneous genetic disorder characterized by bone fragility and deformity, recurrent fractures, blue sclera, short stature, and dentinogenesis imperfecta. Most cases are caused by mutations in COL1A1 and COL1A2 genes. We present a novel splicing mutation in the COL1A1 gene (c.1875+1G>C) in a 16-year-old Brazilian boy diagnosed as a type III osteogenesis imperfecta patient. This splicing mutation and its association with clinical phenotypes will be submitted to the reference database of COL1A1 mutations, which has no other description of this mutation.
Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Nijmegen breakage syndrome (NBS) is a rare DNA repair disorder caused by mutations in the NBS-1 gene (8q21). Patients with this autosomal recessive condition have characteristic facial features, microcephaly present at birth, immunodeficiency, predisposition to malignancy, ionizing radiation hypersensitivity, and growth retardation. We report a 12-year-old boy with NBS associated with porokeratosis; to our knowledge this association has not previously been reported.
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA. firstname.lastname@example.org
The PAX6 gene is a transcription factor expressed early in development, predominantly in the eye, brain and gut. It is well known that mutations in PAX6 may result in aniridia, Peter's anomaly and kertatisis. Here, we present mutation analysis of a patient with aniridia, autism and mental retardation. We identified and characterized a 1.3 Mb deletion that disrupts PAX6 transcriptional activity and deletes additional genes expressed in the brain. Our findings provide continued evidence for the role of PAX6 in neural phenotypes associated with aniridia.
Department of Genetics, University of Medicine and Pharmacy of Craiova, Romania. email@example.com
Darier disease (DD) and Hailey-Hailey disease (HHD) are autosomal dominantly inherited genodermatosis, caused by mutations in ATP2A2 gene and ATP2C1 respectively. We investigated clinical and laboratory two patients - a men with Darier disease and a woman with Hailey-Hailey disease. The patient with Darier disease has mucosal lesions and dental modifications associated with mild mental retardation. At Hailey-Hailey case, the skin lesions are associated with neuropsychiatric and endocrinologic disorders. In both cases, the mutation is inherited from parents. Even if this diseases have similar features, clinical, genetical and histopathological they are distinct entities.
Pauline Chaste, Gudrun Nygren, Henrik Anckarsäter, Maria Råstam, Mary Coleman, Marion Leboyer, Christopher Gillberg, Catalina Betancur
INSERM U513, Université Paris XII, Créteil, France.
Mutations in the Aristaless related homeobox (ARX) gene are associated with a broad spectrum of disorders, including nonsyndromic X-linked mental retardation, sometimes associated with epilepsy, as well as syndromic forms with brain abnormalities and abnormal genitalia. Furthermore, ARX mutations have been described in a few patients with autism or autistic features. In this study, we screened the ARX gene in 226 male patients with autism spectrum disorders and mental retardation; 42 of the patients had epilepsy. The mutation analysis was performed by direct sequencing of all exons and flanking regions. No ARX mutations were identified in any of the patients tested. These findings indicate that mutations in the ARX gene are very rare in autism.(c) 2006 Wiley-Liss, Inc.
J Dermatol. 2006 Aug ;33 (8):550-6 16923137
Dominant dystrophic epidermolysis bullosa caused by a novel G2037R mutation and by a known G2028R mutation in the type VII collagen gene (COL7A1).
Department of Dermatology, Nagoya University Graduate School of Medicine, Aichi, Japan. firstname.lastname@example.org
An autosomal dystrophic epidermolysis bullosa (DDEB) is a hereditary mechanobullous disease characterized by blistering of the skin and the mucous membrane. DDEB is caused by a heterozygous mutation in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils, and phenotypically classified into several types. We experienced two boys with DDEB and examined the mutation analyses of the COL7A1 genes of the two patients and their fathers to clarify the relationship between the genotypes and phenotypes, that is, the mutation sites of COL7A1 gene and the clinical types of DDEB. The case 1 and 2 patients and their fathers revealed a heterozygous nucleotide G to A transition at position 6109 and 6082 in 73 exon of COL7A1, which resulted in a glycine to arginine substitution (G2037R and G2028R), respectively. G2037R found in the case 1 patient was a novel mutation. There was no clear relationship recognized between the two mutation sites in the COL7A1 gene and the clinical variations.