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BACKGROUND: Children born with very low birth weight (VLBW) are at higher risk for cognitive impairment, including language deficits and sensorimotor difficulties. Voice-evoked response (P1m), which has been suggested as a language development biomarker in young children, remains unexplored for its efficacy in VLBW children. Furthermore, the relation between P1m and sensory difficulties in VLBW children remains unclear. METHODS: 40 children with VLBW were recruited at 5-to-6 years old (26 male, 14 female, mean age of months ± SD, 80.0 ± 4.9). We measured their voice-evoked brain response using child-customized magnetoencephalography (MEG) and examined the relation between P1m and language conceptual inference ability and sensory characteristics. RESULTS: The final sample comprised 36 children (23 boys, 13 girls; ages 61-86 months; gestational ages 24-36 weeks). As a result of multiple regression analysis, voice-evoked P1m in the left hemisphere was correlated significantly with language ability (ß = 0.414 P = 0.015) and sensory hypersensitivity (ß = 0.471 P = 0.005). CONCLUSION: Our findings indicate that the relation between P1m and language conceptual inference ability observed in term children in earlier studies is replicated in VLBW children, and suggests P1m intensity as a biomarker of sensory sensitivity characteristics. IMPACT: We investigated brain functions related to language development and sensory problems in very low birth-weight children. In very low birth weight children at early school age, brain responses to human voices are associated with language conceptual inference ability and sensory hypersensitivity. These findings promote a physiological understanding of both language development and sensory characteristics in very low birth weight children.
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A number of studies have been made on the sleep characteristics of children born preterm in an attempt to develop methods to address the sleep problems commonly observed among such children. However, the reported sleep characteristics from these studies vary depending on the observation methods used, i.e., actigraphy, polysomnography and questionnaire. In the current study, to obtain reliable data on the sleep characteristics of preterm-born children, we investigated the difference in sleep properties between 97 preterm and 97 term toddlers of approximately 1.5 years of age using actigraphy. Actigraphy units were attached to the toddlers' waists with an adjustable elastic belt for 7 consecutive days, and a child sleep diary was completed by their parents. In the study, we found that preterm toddlers had more nocturnal awakenings and more daytime activity, suggesting that preterm-born children may have a different process of sleep development in their early development.
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Qualidade do Sono , Sono , Pré-Escolar , Humanos , Recém-Nascido , Actigrafia , Polissonografia , Recém-Nascido PrematuroRESUMO
Our recent study on full-term toddlers demonstrated that daytime nap properties affect the distribution ratio between nap and nighttime sleep duration in total sleep time but does not affect the overall total amount of daily sleep time. However, there is still no clear scientific consensus as to whether the ratio between naps and nighttime sleep or just daily total sleep duration itself is more important for healthy child development. In the current study, to gain an answer to this question, we examined the relationship between the sleep properties and the cognitive development of toddlers born prematurely using actigraphy and the Kyoto scale of psychological development (KSPD) test. 101 premature toddlers of approximately 1.5 years of age were recruited for the study. Actigraphy units were attached to their waist with an adjustable elastic belt for 7 consecutive days and a child sleep diary was completed by their parents. In the study, we found no significant correlation between either nap or nighttime sleep duration and cognitive development of the preterm toddlers. In contrast, we found that stable daily wake time was significantly associated with better cognitive development, suggesting that sleep regulation may contribute to the brain maturation of preterm toddlers.
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Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Sono/fisiologia , Actigrafia/métodos , Feminino , Humanos , Lactente , Recém-Nascido Prematuro/crescimento & desenvolvimento , Masculino , Polissonografia/métodos , Fatores de Tempo , Vigília/fisiologiaRESUMO
The greater omentum is an apron-like peritoneal mesothelial sheet that was described by ultrasound as a floating fluid-filled viscus in ascites during the fetal period. To examine the association between the etiology of fetal ascites and ultrasound findings of the greater omentum, a retrospective study was conducted. Ultrasound findings of fetal omentum were defined as follows: (1) a cyst-like shape with a thin membrane observed as wavy in the ascites, (2) beside the stomach and below the liver, and (3) no blood flow noted on color Doppler. Eleven pregnancies had fetal ascites. A fetal greater omentum was confirmed in eight cases in which ascites were caused by non-peritonitis: fetal hydrops (n = 4), congenital cytomegalovirus infection (n = 2), idiopathic chylous ascites (n = 1), and unknown cause (n = 1). Of these eight cases, no abdominal surgical management was required in three live babies. However, a fetal greater omentum was not confirmed in all three cases of meconium peritonitis. It was suggested that the finding of the greater omentum can be an important clue for estimating the pathophysiological etiology of fetal ascites and helping with postnatal management. It should be reasonable to add the finding of the greater omentum to the detailed ultrasound examination checklist.
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The purpose of the present study is to examine the association between toddlers' sleep arrangements and their nighttime sleep duration and other sleep variables. For this investigation, we performed a study in which child activity and sleep levels were recorded using actigraphy. The parents of 1.5-year-old toddlers (n = 106) were asked to attach an actigraphy unit to their child's waist with an adjustable elastic belt and complete a sleep diary for 7 consecutive days. Questionnaires were used to assess the sleep arrangements of the toddlers. There was a significant negative correlation between nap duration and nighttime sleep duration, suggesting that longer nap sleep induces shorter nighttime sleep duration. Among the sleep arrangements, such as nighttime breastfeeding or co-sleeping, only nighttime breastfeeding predicted shorter nighttime sleep duration. Our findings indicate that shorter naps induce a longer nighttime sleep in 1.5-year-old toddlers while nighttime breastfeeding decreases their nighttime sleep duration.
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Aleitamento Materno , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Sono/fisiologia , Actigrafia , Pré-Escolar , Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Inquéritos e Questionários , Fatores de TempoRESUMO
BACKGROUND: Variants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear. METHODS: We examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail. RESULTS: Pathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly. CONCLUSIONS: Prenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.
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Colágeno Tipo IV/genética , Mutação/genética , Síndrome de Dandy-Walker/genética , Feminino , Humanos , Masculino , Gravidez , Ultrassonografia Pré-Natal/métodosRESUMO
Background: Neonatal hemochromatosis (NH) is a rare but serious disease causing fulminant hepatic failure. The recurrence rate of NH in a subsequent infant of a mother with an affected infant is 70-90%. Recently, antenatal maternal high-dose intravenous immunoglobulin (IVIG) treatment has been reported to be effective for preventing NH recurrence. However, data on the IgG concentrations during this treatment are limited.Objective: We report a Japanese experience and present a pharmacokinetic simulation model of IgG during IVIG treatment.Methods: Women with histories of pregnancy diagnosed with NH were treated with IVIG weekly from the second trimester until the end of gestation. Serum IgG levels during treatment were collected frequently and pharmacokinetics were simulated by a two-compartment model.Results: Six women were included during eight pregnancies. None experienced severe adverse events. Three out of eight infants showed temporary liver dysfunction, but none required any treatment. A simulation study showed that the estimated trough and peak levels of IgG concentrations during IVIG were 2000-3000 and 4000-5000 mg/dl, respectively.Conclusion: This treatment prevented the recurrence of NH in siblings in Japanese women. We examined the details of serum IgG concentrations and introduced a new pharmacokinetic simulation model of IgG concentrations during IVIG treatment.
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Hemocromatose/prevenção & controle , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/farmacocinética , Cuidado Pré-Natal/métodos , Prevenção Secundária/métodos , Adulto , Quimioprevenção/métodos , Relação Dose-Resposta a Droga , Feminino , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Recém-Nascido , Infusões Intravenosas , Japão , Gravidez , Resultado da Gravidez , Recidiva , História Reprodutiva , Estudos Retrospectivos , Irmãos , Resultado do TratamentoRESUMO
The amniotic membrane plays an important role in the physiological maintenance and protection of the embryo. Indeed, dysfunction of the amniotic membrane is thought to have an adverse effect on the continuation of pregnancy. In this report, we examined the pathological changes in the amniotic epithelium in three cases of diffuse chorioamniotic hemosiderosis (DCH) and investigated the cause of necrosis of the amniotic epithelial cells and its relationship with oligohydramnios. Diffuse chorioamniotic hemosiderosis was confirmed in all three cases. More extensive amniotic epithelial necrosis led to more severe hemosiderosis. Immunostaining for 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress, was positive in the amniotic epithelial cells. We speculate that oxidative DNA damage of the amniotic epithelium occurs by decomposition products of blood cells in cases accompanying subchorionic hematomas and pathological DCH. Furthermore, disorder of the amniotic epithelium may disrupt the balance of the amniotic fluid volume and cause oligohydramnios.
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Corioamnionite/patologia , Epitélio/patologia , Hemossiderose/patologia , Estresse Oxidativo , Placenta/patologia , Adulto , Feminino , Humanos , GravidezRESUMO
We report a case of twin anemia-polycythemia sequence with blood chimerism in monochorionic dizygotic twins born to a 30-year-old woman who conceived via ovulation induction. The neonates developed twin anemia-polycythemia sequence; the female twin had anemia and the male had polycythemia. We detected blood chimerism using fluorescence in situ hybridization (FISH). Twin anemia-polycythemia sequence carries not only perinatal risks, but also genetic and immunological implications due to blood chimerism. Although previous reports have described twin-to-twin transfusion syndrome in monochorionic dizygotic twins, we report the first case of twin anemia-polycythemia sequence in monochorionic dizygotic twins.
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Anemia Neonatal/diagnóstico , Quimerismo , Doenças em Gêmeos/diagnóstico , Policitemia/diagnóstico , Gêmeos Dizigóticos , Adulto , Córion , Feminino , Humanos , Recém-Nascido , Masculino , GravidezAssuntos
Obstrução Duodenal/diagnóstico , Obstrução Duodenal/genética , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Atresia Intestinal/diagnóstico , Atresia Intestinal/genética , Perfuração Intestinal/congênito , Perfuração Intestinal/diagnóstico , Fenótipo , Biomarcadores , Biópsia , Obstrução Duodenal/cirurgia , Displasia Ectodérmica/cirurgia , Doenças Genéticas Ligadas ao Cromossomo X/cirurgia , Humanos , Síndromes de Imunodeficiência/cirurgia , Recém-Nascido , Atresia Intestinal/cirurgia , Perfuração Intestinal/cirurgia , Masculino , Doenças da Imunodeficiência Primária , Radiografia , Resultado do TratamentoRESUMO
Recent reports showed that neoadjuvant chemotherapy (NAC) has been successfully applied to treat advanced uterine cervical cancers during pregnancy. However, its side effects on the fetus remain unclear. Here, we report a 33-year-old primipara who underwent four courses of NAC therapy, paclitaxel and cisplatin, from 17 to 27 weeks of gestation due to uterine cervical cancer stage IB2. At 31 weeks of gestation, cesarean section and radical hysterectomy were performed, and a female baby weighing 1446 g was born. Although pre- and postnatal courses were uneventful, neonatal erythroderma over the entire body was observed just after delivery. The pathological diagnosis was ichthyosiform erythroderma, which was later demonstrated to be keratitis-ichthyosis-deafness syndrome, by exome sequencing analysis. Although her skin disorder was consistent with keratitis-ichthyosis-deafness syndrome, the skin condition gradually improved after delivery. These findings suggest that NAC therapy during pregnancy might cause or exacerbate systemic skin lesions in the fetus/neonate.
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Antineoplásicos/efeitos adversos , Eritrodermia Ictiosiforme Congênita/induzido quimicamente , Ceratite/induzido quimicamente , Complicações Neoplásicas na Gravidez , Neoplasias do Colo do Útero , Adulto , Cesárea , Quimioterapia Adjuvante/efeitos adversos , Feminino , Humanos , Histerectomia , Recém-Nascido , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/cirurgia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgiaRESUMO
OBJECTIVE: To investigate the utility of serum pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) as a diagnostic marker of hypophosphatasia (HPP) and an indicator of the effect of, and patient compliance with, enzyme replacement therapy (ERT), we measured PLP, PL, and PA concentrations in serum samples from HPP patients with and without ERT. METHODS: Blood samples were collected from HPP patients and serum was frozen as soon as possible (mostly within one hour). PLP, PL, and PA concentrations were analyzed using high-performance liquid chromatography with fluorescence detection after pre-column derivatization by semicarbazide. We investigated which metabolites are associated with clinical phenotypes and how these metabolites change with ERT. RESULTS: Serum samples from 20 HPP patients were analyzed. The PLP-to-PL ratio and PLP concentration were elevated in all HPP patients. They correlated negatively with serum alkaline phosphatase (ALP) activity and showed higher values in more severe phenotypes (perinatal severe and infantile HPP) compared with other phenotypes. PL concentration was reduced only in perinatal severe HPP. ERT reduced the PLP-to-PL ratio to mildly reduced or low-normal levels and the PLP concentration was reduced to normal or mildly elevated levels. Urine phosphoethanolamine (PEA) concentration did not return to normal levels with ERT in most patients. CONCLUSIONS: The serum PLP-to-PL ratio is a better indicator of the effect of ERT for HPP than serum PLP and urine PEA concentrations, and a PLP-to-PL ratio of <4.0 is a good indicator of the effect of, and patient compliance with, ERT.
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Fosfatase Alcalina/genética , Terapia de Reposição de Enzimas , Hipofosfatasia/tratamento farmacológico , Imunoglobulina G/genética , Fosfato de Piridoxal/sangue , Proteínas Recombinantes de Fusão/genética , Adolescente , Adulto , Fosfatase Alcalina/sangue , Fosfatase Alcalina/uso terapêutico , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Etanolaminas/urina , Feminino , Humanos , Hipofosfatasia/sangue , Hipofosfatasia/patologia , Hipofosfatasia/urina , Imunoglobulina G/uso terapêutico , Lactente , Recém-Nascido , Masculino , Piridoxal/sangue , Ácido Piridóxico/sangue , Proteínas Recombinantes de Fusão/uso terapêutico , Vitamina B 6/metabolismo , Adulto JovemAssuntos
Leucemia Mieloide Aguda/genética , Regressão Neoplásica Espontânea , Proteínas de Fusão Oncogênica/genética , Neoplasias Cutâneas/genética , Medula Óssea/patologia , Proteína p300 Associada a E1A/genética , Feminino , Rearranjo Gênico , Histona Acetiltransferases/genética , Humanos , Recém-Nascido , Leucemia Mieloide Aguda/congênito , Leucemia Mieloide Aguda/patologia , Neoplasias Cutâneas/congênito , Neoplasias Cutâneas/patologiaRESUMO
The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) (MIM# 603736) and genitopatellar syndrome (GPS) (MIM#606170) are allelic diseases caused by KAT6B mutation. Genotype-phenotype correlation is assumed, but a few patients manifest overlapping features of both syndromes. Here we report the case of a boy with SBBYSS. He had a KAT6B mutation previously reported in typical SBBYSS, but he also manifested severe developmental delay, as well as genital features and laryngomalacia requiring tracheostomy that conformed to GPS.
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Blefarofimose/diagnóstico , Blefarofimose/genética , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/genética , Duplicação Gênica , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Histona Acetiltransferases/genética , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Sequências Repetidas Invertidas , Instabilidade Articular/diagnóstico , Instabilidade Articular/genética , Alelos , Anormalidades Craniofaciais/diagnóstico , Análise Mutacional de DNA , Diagnóstico Diferencial , Éxons , Fácies , Estudos de Associação Genética , Humanos , Recém-Nascido , Rim/anormalidades , Masculino , Mutação , Patela/anormalidades , Fenótipo , Transtornos Psicomotores/diagnóstico , Radiografia , Escroto/anormalidades , Ultrassonografia Pré-Natal , Anormalidades Urogenitais/diagnósticoRESUMO
BACKGROUND: Infantile neuronal ceroid lipofuscinosis (INCL) is an autosomal recessive disorder starting in infancy as early as 12-month-old, caused by PPT1 (palmitoyl-protein thioesterase 1) mutations, and characterized by progressive psychomotor deterioration, brain atrophy, myoclonic jerk and visual impairment. INCL can be diagnosed by brain magnetic resonance image (MRI) prior to rapid deterioration stage. To date, there is no INCL patient whose manifestation was caused by uniparental isodisomy (UPiD). PATIENT: We reported a girl diagnosed with INCL. Genetic analysis revealed a novel PPT1 mutation c.20_47del28:p.Leu7Hisfs*21. Only the father of the patient was found as a carrier of this mutation. SNP array showed the mutation became homozygous by paternal UPiD of chromosome 1. DISCUSSION: Although ICNL is a rare disease except in Finland, it is not difficult to diagnose it since the clinical symptoms and MRI findings are characteristic. Genetic testing is useful for definitive diagnosis, and distinction of UPiD is essential for genetic counseling.
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Cromossomos Humanos Par 1 , Proteínas de Membrana/genética , Lipofuscinoses Ceroides Neuronais/genética , Lipofuscinoses Ceroides Neuronais/fisiopatologia , Dissomia Uniparental/genética , Dissomia Uniparental/fisiopatologia , Encéfalo/diagnóstico por imagem , Pré-Escolar , Diagnóstico Diferencial , Feminino , Mutação da Fase de Leitura , Humanos , Lactente , Imageamento por Ressonância Magnética , Lipofuscinoses Ceroides Neuronais/diagnóstico , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Tioléster Hidrolases , Dissomia Uniparental/diagnósticoRESUMO
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by multiple hamartias and hamartomas involving throughout the body. To date, many TSC1 and TSC2 mutations have been reported all over the world, however, few TSC mutation studies have been performed in the Japanese population, and genetic characteristics of Japanese TSC patients are not yet clear. In this study, we analyzed TSC1 and TSC2 in 57 Japanese patients with TSC (8 familial and 49 sporadic; 46 definite and 11 suspect TSC) and identified 31 mutations including 11 TSC1 mutations (two familial and nine sporadic; all definite TSC) and 20 TSC2 mutations (2 familial and 18 sporadic; 19 definite and 1 suspect TSC). We also reviewed all Japanese TSC mutations previously reported. Our study demonstrates significantly higher incidence (P=0.007) of TSC1 mutations among sporadic TSC patients in the Japanese population compared with US and European studies. No differences emerged in mutation distributions and types in precedent studies, excepting low frequency of the TSC2 nonsense mutation. Comparing clinical manifestations, developmental delay and/or mental retardation were milder in TSC1 patients than TSC2 patients for its frequency (P=0.032) and severity (P=0.015); however, no other symptoms were clearly different.
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Povo Asiático/genética , Mutação , Esclerose Tuberosa/etnologia , Esclerose Tuberosa/genética , Proteínas Supressoras de Tumor/genética , Análise Mutacional de DNA/métodos , Humanos , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose TuberosaRESUMO
Establishing a simple and effective mutation screening method is one of the most compelling problems with applying genetic diagnosis to clinical use. Because there is no reliable and inexpensive screening system, amplifying by PCR and performing direct sequencing of every coding exon is the gold standard strategy even today. However, this approach is expensive and time consuming, especially when gene size or sample number is large. Previously, we developed CEL nuclease mediated heteroduplex incision with polyacrylamide gel electrophoresis and silver staining (CHIPS) as an ideal simple mutation screening system constructed with only conventional apparatuses and commercially available reagents. In this study, we evaluated the utility of CHIPS technology for genetic diagnosis in clinical practice by applying this system to screening for the COL2A1, WRN and RPS6KA3 mutations in newly diagnosed patients with Stickler syndrome (autosomal dominant inheritance), Werner syndrome (autosomal recessive inheritance) and Coffin-Lowry syndrome (X-linked inheritance), respectively. In all three genes, CHIPS detected all DNA variations including disease causative mutations within a day. Direct sequencing of all coding exons of these genes confirmed 100% sensitivity and specificity. We demonstrate high sensitivity, high cost performance and reliability of this simple system, with compatibility to all inheritance modes. Because of its low technology, CHIPS is ready to use and potentially disseminate to any laboratories in the world.
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Artrite/diagnóstico , Bioensaio , Síndrome de Coffin-Lowry/diagnóstico , Doenças do Tecido Conjuntivo/diagnóstico , Perda Auditiva Neurossensorial/diagnóstico , Ácidos Nucleicos Heteroduplexes/análise , Descolamento Retiniano/diagnóstico , Síndrome de Werner/diagnóstico , Artrite/genética , Sequência de Bases , Pré-Escolar , Síndrome de Coffin-Lowry/genética , Colágeno Tipo II/genética , Doenças do Tecido Conjuntivo/genética , Enzimas de Restrição do DNA/metabolismo , Eletroforese em Gel de Poliacrilamida , Exodesoxirribonucleases/genética , Éxons , Perda Auditiva Neurossensorial/genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , RecQ Helicases/genética , Reprodutibilidade dos Testes , Descolamento Retiniano/genética , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Sensibilidade e Especificidade , Coloração pela Prata , Síndrome de Werner/genética , Helicase da Síndrome de WernerRESUMO
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency of the enzyme arylsulfatase A encoded by the ARSA gene located on 22q13.33. Typically, in autosomal recessive disease, a patient inherits two mutations from both parents who are heterozygous carriers. However, in some instances, it is possible to develop the disease by uniparental isodisomy (UPiD), in which two copies of the same mutated allele are inherited from only one carrier parent. Here, we report the first patient with MLD caused by UPiD of chromosome 22. The patient has a homozygous missense mutation, P136T, on ARSA. Family study of the ARSA gene and leukocyte enzyme activity revealed that his father and sister were heterozygous carriers, but his mother possessed only wild-type alleles and normal enzyme activity. Karyotypes of the patient and the parents were normal. Microsatellite analysis showed no discrepancy of parentage, and paternal UPiD of chromosome 22 was indicated. Finally, genome-wide single-nucleotide polymorphism array confirmed the region of UPiD was extended to the entire chromosome 22 of the patient.