RESUMEN
Ring chromosomes are uncommon cytogenetic findings but have meanwhile been reported for nearly all human chromosomes. Among the rare observations of ring chromosomes in man, the diagnosis of ring chromosome 18 represents a prominent group. We here describe on the cytogenetic analysis results obtained for a 9 years old male patient of non-consanguineous parents. He had growth and developmental delay, mental and motor retardation, microcephaly, microphtalmia, triangle face, small dysplastic ears, strabismus, epicanthal folds on the left, short stature, cryptorchidism, spasticity, pes equinovarus, pes planus, hypothroidism, stereotypic movements and febrile seizures. Also he had hypomyelinization and multiple hyperintense focuses within the white matter on the MRI. The generalized epileptiform abnormality originated from bilateral Centroparietal region. The metabolic investigations including blood and urine amino acids and lysosomal screening tests were normal. The chromosome analysis identified [46,XY,r(18)/46,XY] in 35% of cells a ring 18 and in 65% of cells normal karyotype in peripheral blood cells examined by standard G-bands by Trypsin using Giemsa (GTG) analysis. The dysmorphic features of the presented patient are discussed to the identification of the genotype-phenotype correlation related to his karyotype.
Asunto(s)
Encéfalo/patología , Discapacidad Intelectual/genética , Imagen por Resonancia Magnética , Cromosomas en Anillo , Convulsiones Febriles/genética , Niño , Cromosomas Humanos Par 18 , Estudios de Asociación Genética , Humanos , Discapacidad Intelectual/patología , Cariotipificación , MasculinoRESUMEN
Monilethrix, a rare autosomal dominant disease characterized by hair fragility and follicular hyperkeratosis, is caused by mutations in three type II hair cortex keratins. The human keratin family comprises 54 members, 28 type I and 26 type II. The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. In our study, Monilethrix was diagnosed on the basis of clinical characteristics and microscopic examination in a family with 11 affected members. Haplotype analysis was performed by three Simple Tandem Repeat markers (STR) and KRT86 gene was sequenced for the identification of the disease causing mutation. In the results of this, autosomal dominant mutation (E402K) in exon 7 of KRT86 gene was identified as a cause of Moniltherix in the large family from Turkey.
Asunto(s)
Pruebas Genéticas/métodos , Enfermedades del Cabello/prevención & control , Queratinas Específicas del Pelo/genética , Queratinas Tipo II/genética , Preescolar , Mapeo Cromosómico , Consanguinidad , Salud de la Familia , Femenino , Enfermedades del Cabello/genética , Haplotipos/genética , Humanos , Masculino , Linaje , Polimorfismo de Nucleótido Simple , TurquíaRESUMEN
Hereditary hearing impairment is a genetically heterogeneous disorder. To date, 49 autosomal recessive nonsyndromic hearing impairment (ARNSHI) loci have been described, and there are more than 16 additional loci announced. In 25 of the known loci, causative genes have been identified. A genome scan and fine mapping revealed a novel locus for ARNSHI (DFNB63) on chromosome 11q13.2-q13.4 in a five-generation Turkish family (TR57). The homozygous linkage interval is flanked by the markers D11S1337 and D11S2371 and spans a 5.3-Mb interval. A maximum two-point log of odds score of 6.27 at a recombination fraction of theta = 0.0 was calculated for the marker D11S4139. DFNB63 represents the eighth ARNSHI locus mapped to chromosome 11, and about 3.33 Mb separate the DFNB63 region from MYO7A (DFNB2/DFNB11). Sequencing of coding regions and exon-intron boundaries of 13 candidate genes, namely SHANK2, CTTN, TPCN2, FGF3, FGF4, FGF19, FCHSD2, PHR1, TMEM16A, RAB6A, MYEOV, P2RY2 and KIAA0280, in genomic DNA from an affected individual of family TR57 revealed no disease-causing mutations.
Asunto(s)
Cromosomas Humanos Par 11/genética , Pérdida Auditiva/genética , Mapeo Cromosómico , Consanguinidad , Genes Recesivos , Genotipo , Pérdida Auditiva/congénito , Humanos , Repeticiones de Microsatélite , LinajeRESUMEN
Mutations in the transmembrane channel-like gene 1 (TMC1) cause prelingual autosomal recessive (DFNB7/11) and postlingual progressive autosomal dominant (DFNA36) nonsyndromic hearing loss. To determine the genetic causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) in the northeast and east of Turkey, 65 unrelated families without mutations in the protein coding region of the GJB2 (GJB2-negative) were analyzed. A genomewide scan for homozygosity and linkage analysis in one of these families revealed a 13.2 cM critical region between D9S273 and D9S153 at chromosome 9p13.2-q21.31 with a maximum two-point lod score of 4.00 at theta=0.0 for marker D9S175. TMC1 is in this critical region. Homozygosity screening with intragenic markers for TMC1 in the remaining 64 families suggested involvement of this gene in three additional families. Subsequent sequencing of TMC1 in these four families revealed four novel homozygous mutations, c.776A>G [p.Tyr259Cys], c.821C>T [p.Pro274Leu], c.1334G>A [p.Arg445His], and c.1083_1087delCAGAT [p.Arg362ProfrX6]. Our results indicate that TMC1 mutations account for at least 6% (4/65) of ARNSHL in GJB2-negative Turkish families from the northeast and east of Turkey.
Asunto(s)
Mutación del Sistema de Lectura , Pérdida Auditiva/genética , Proteínas de la Membrana/genética , Mutación Missense , Secuencia de Aminoácidos , Conexina 26 , Conexinas/genética , Análisis Mutacional de ADN , Femenino , Ligamiento Genético , Pruebas Genéticas , Haplotipos , Pérdida Auditiva/congénito , Humanos , Masculino , Proteínas de la Membrana/química , Datos de Secuencia Molecular , Linaje , Alineación de Secuencia , TurquíaRESUMEN
Homozygosity mapping and linkage analysis in a Turkish family with autosomal recessive prelingual sensorineural hearing loss revealed a 15-cM critical region at 17q25.1-25.3 flanked by the polymorphic markers D17S1807 and D17S1806. The maximum two-point lod score was 4.07 at theta=0.0 for the marker D17S801. The linkage interval contains the Usher syndrome 1G gene (USH1G) that is mutated in patients with Usher syndrome (USH) type 1g and encodes the SANS protein. Mutation analysis of USH1G led to the identification of a homozygous missense mutation D458V at the -3 position of the PDZ binding motif of SANS. This mutation was also present homozygously in one out of 64 additional families from Turkey with autosomal recessive nonsyndromic hearing loss and heterozygously in one out of 498 control chromosomes. By molecular modeling, we provide evidence that this mutation impairs the interaction of SANS with harmonin. Ophthalmologic examination and vestibular evaluation of patients from both families revealed mild retinitis pigmentosa and normal vestibular function. These results suggest that these patients suffer from atypical USH.
Asunto(s)
Pérdida Auditiva Sensorineural/genética , Mutación Missense , Proteínas del Tejido Nervioso/genética , Síndromes de Usher/genética , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Audiometría de Tonos Puros , Mapeo Cromosómico , Cromosomas Humanos Par 17 , Consanguinidad , Análisis Mutacional de ADN , Exones , Femenino , Genes Recesivos , Ligamiento Genético , Marcadores Genéticos , Haplotipos , Homocigoto , Humanos , Enlace de Hidrógeno , Escala de Lod , Masculino , Modelos Moleculares , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/química , Linaje , Polimorfismo Genético , Estructura Terciaria de Proteína , Secuencias Repetidas en Tándem , Turquía/epidemiologíaRESUMEN
Detection of an unbalanced t(4;15) by FISH in a child with multiple congenital anomalies: In this report, we present the clinical history and findings in a 6-month-old male with multiple congenital anomalies, developmental delay, and an initial male karyotype with 4q+. The origin of the additional segment on 4q was unequivocally established by fluorescence in situ hybridization (FISH). Whole chromosome probe for chromosome 4 and chromosome 15-specific a-satellite probe were used. The karyotype was demonstrated to be 46,XY,der(4), t(4;15)(q35;?),inv(9)(p13q13). To the best of our knowledge the above cytogenetic abnormalities with these clinical findings have not been described previously. This case further demonstrates the advantage of FISH in the identification of anomalous chromosome regions and breakpoints.
Asunto(s)
Anomalías Múltiples/genética , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 4 , Hibridación Fluorescente in Situ , Translocación Genética , Humanos , Lactante , Cariotipificación , MasculinoRESUMEN
This study was carried out to determine the frequency of congenital heart defects, cholelithiasis, hypothyroidism and leukemia in 31 children with Down syndrome. Twenty children (71.4%) had congenital heart defects. Ultrasonography was performed on 29 and two of these (6.9%) had cholelithiasis. Tests for hypothyroidism in 24 children identified hypothyroidism in three (12.5%). Leukemia was diagnosed in three children (10%) (one with congenital, two acquired). One patient with congenital hypothyroidism underwent surgery on the third day of life because of annular pancreas and duodenal atresia.
Asunto(s)
Colelitiasis/etiología , Síndrome de Down/complicaciones , Cardiopatías Congénitas/etiología , Hipotiroidismo/etiología , Leucemia/etiología , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , TurquíaRESUMEN
A 36-year-old normal healthy female was karyotyped because all of her five pregnancies had terminated in spontaneous abortions during the first 3 mo. Cytogenetic investigation disclosed a female karyotype with isochromosomes of 2p and 2q replacing the two normal chromosomes 2. Her husband and both of her parents had normal karyotypes. Molecular studies revealed maternal only inheritance for chromosome 2 markers. Reduction to homozygosity of all informative markers indicated that the isochromosomes derived from a single maternal chromosome 2. Except for the possibility of homozygosity for recessive mutations, maternal uniparental disomy 2 appears to have no adverse impact on the phenotype. Our data indicate that no maternally imprinted genes with major effect map to chromosome 2.
Asunto(s)
Aborto Espontáneo/genética , Cromosomas Humanos Par 2 , Isocromosomas , Adulto , Femenino , Impresión Genómica , Humanos , Cariotipificación , Madres , Fenotipo , EmbarazoRESUMEN
We describe a 2-year-old female patient who had megaloblastic anaemia caused by selective vitamin B12 malabsorption (Imerslund-Grasbeck syndrome) and del(21)(q22). To our knowledge, this is the first observation of Imerslund-Grasbeck syndrome associated with del(21)(q22) in the literature.
Asunto(s)
Anemia Megaloblástica/genética , Aberraciones Cromosómicas/genética , Deleción Cromosómica , Cromosomas Humanos Par 21/genética , Deficiencia de Vitamina B 12/genética , Preescolar , Trastornos de los Cromosomas , Consanguinidad , Femenino , Humanos , Cariotipificación , Linaje , SíndromeRESUMEN
Sea gull faeces (616 samples in toto) were examined for enteric human pathogens, and 1.3% and 0.60% were found to contain Salmonella spp. and Shigella spp., respectively. All positive samples were near sewage outfalls and refuse tips. The Salmonella serotype was isolated as S. typhi and the Shigella serotype as S. sonnei. Pathogenic bacteria were isolated from the faecal samples collected only in the Trabzon area.
Asunto(s)
Aves/microbiología , Heces/microbiología , Salmonella typhi/aislamiento & purificación , Shigella sonnei/aislamiento & purificación , Animales , Vectores de Enfermedades , TurquíaRESUMEN
This study involved 999 married women, aged between 15 and 49, at the twelve health centres in the province of Trabzon in order to determine the ratio of consanguineous marriages, the factors affecting this situation, the ratios of abortion and the mortality of children in the first year. This ratio of consanguineous marriages was found 20 percent. The education levels of the great majority of these were low. The average age was 18. These were most frequently between children of paternal aunts and maternal uncles (39%) and these marriages, the ratio of abortion and children mortality were higher than others (P less than 0.05). Furthermore, it has been established that the kind of marriage has considerably decreased in Trabzon lately, but we believe that this reduction will be higher in the future since the education levels rapidly increase.
Asunto(s)
Consanguinidad , Matrimonio/estadística & datos numéricos , Aborto Espontáneo/epidemiología , Adolescente , Adulto , Anciano , Recolección de Datos , Escolaridad , Femenino , Humanos , Mortalidad Infantil , Recién Nacido , Embarazo , Turquía/epidemiologíaRESUMEN
In this study we presented 92 cases with regional lymphadenitis (over 1 cm in diameter) which was caused by BCG vaccination generally performed a few days after birth. The patients were divided into four therapy groups. In group I, the lymphadenitis in 26 cases was excised totally by a surgical operation and they improved in a median period of four weeks (average: 4.4). No therapy was applied in 33 patients constituting group II and their periods of improvement were 28 weeks (average: 29.1). Sixteen cases in group III were given isoniazid (INH) 10 mg/kg for six months in addition to total surgical excision and their healing period was 4.5 weeks (average: 4). Seventeen cases in group IV were administered only INH for six months and the median improvement period was found to be 27 weeks (average: 28.2). The statistical differences in terms of the improvement periods between groups I and III, and groups II and IV were found to be insignificant (p greater than 0.05) but these differences were significant between groups I and II, groups I and IV, groups II and III, and groups III and IV (p less than 0.05). These results show that spontaneous healing is possible. Total excision is the best therapy for BCG lymphadenitis in suppurative forms and INH has no effect in shortening the therapy period.