RESUMEN
Hearing loss is the most frequent sensorineural disorder affecting 1 in 1000 newborns. In more than half of these babies, the hearing loss is inherited. Hereditary hearing loss is a very heterogeneous trait with about 100 gene localizations and 44 gene identifications for non-syndromic hearing loss. Transmembrane channel-like gene 1 (TMC1) has been identified as the disease-causing gene for autosomal dominant and autosomal recessive non-syndromic hearing loss at the DFNA36 and DFNB7/11 loci, respectively. To date, 2 dominant and 18 recessive TMC1 mutations have been reported as the cause of hearing loss in 34 families. In this report, we describe linkage to DFNA36 and DFNB7/11 in 1 family with dominant and 10 families with recessive non-syndromic sensorineural hearing loss. In addition, mutation analysis of TMC1 was performed in 51 familial Turkish patients with autosomal recessive hearing loss. TMC1 mutations were identified in seven of the families segregating recessive hearing loss. The pathogenic variants we found included two known mutations, c.100C>T and c.1165C>T, and four new mutations, c.2350C>T, c.776+1G>A, c.767delT and c.1166G>A. The absence of TMC1 mutations in the remaining six linked families implies the presence of mutations outside the coding region of this gene or alternatively at least one additional deafness-causing gene in this region. The analysis of copy number variations in TMC1 as well as DNA sequencing of 15 additional candidate genes did not reveal any proven pathogenic changes, leaving both hypotheses open.
Asunto(s)
Sordera/genética , Ligamiento Genético , Pérdida Auditiva/genética , Proteínas de la Membrana/genética , Mutación , Análisis Mutacional de ADN , Exones , Familia , Dosificación de Gen , HumanosRESUMEN
We describe a female patient with a small supernumerary marker chromosome (sSMC) present in mosaic and characterized in detail by fluorescence in situ hybridization (FISH) using all 24 human whole chromosome painting probes, multicolor banding (MCB) and subcentromere specific multicolor FISH (subcenM-FISH). The sSMC was demonstrated to be derived from chromosome 5 and the karyotype of our patient was as follows: 47,XX,+mar.ish r(5)(::p13.2 approximately p13.3-->q11.2::) [60%]/46,XX [40%]. Partial trisomy for the proximal 5p and q chromosomal regions is a rare event. A critical region exists at 5p13 for the phenotype associated with duplication 5p. As far as we know, eight similar cases have been published up to now. We describe a new case which, to our knowledge, is the first characterized in such detail. The role of uniparental disomy (UPD) in cases of SMC is also discussed.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 6 , Anomalías Craneofaciales/genética , Cardiopatías Congénitas/genética , Anomalías Múltiples/genética , Niño , Mapeo Cromosómico , Femenino , Marcadores Genéticos , Humanos , Hibridación Fluorescente in Situ , CariotipificaciónRESUMEN
We report a case of Angelman syndrome (AS) with paternal uniparental disomy (pUPD) of chromosome 15. This 6-year-old girl with overgrowth had frequent, but only provoked laughter, was mildly ataxic with limb hypertonia, and had no intelligible speech. She had deep-set eyes, protruding tongue, and prominent chin. The karyotype was normal. DNA analysis with microsatellites from chromosome 15 showed no inheritance of maternal alleles both within and outside the AS critical region. Proximal markers showed reduction to homozygosity of paternal alleles, intermediate markers showed nonreduction, and distal markers reduction, thus suggesting a meiosis II nondisjunction event in the father with two crossovers. This is, to our knowledge, the first reported case of AS due to meiosis II nondisjunction. We present detailed physical measurements in this patient, adding to the clinical description of the milder phenotype in AS due to pUPD.
Asunto(s)
Síndrome de Angelman/genética , Aberraciones Cromosómicas , No Disyunción Genética , Niño , Mapeo Cromosómico , Cromosomas Humanos Par 15 , Femenino , Humanos , Meiosis , Repeticiones de Microsatélite/genéticaRESUMEN
Partial trisomy 17q22-qter is a rare but well-recognized clinical entity. We present a case of partial trisomy for the long arm of chromosome 17, which was detected in a female infant with severe psychomotor and somatic retardation, Stargardt disease, short limbs, and numerous minor anomalies. Differential chromosomal staining demonstrated an excess of genetic material on the long arm of the late replicating X chromosome. FISH and DNA polymorphism analysis showed that the extra material belonged to the distal part of the long arm of chromosome 17 and that there was a partial monosomy of the distal part of the long arm of the derivative X chromosome. The breakpoint regions of this translocation were identified by molecular analysis using polymorphic microsatellite markers on human chromosomes 17 and X. The origin of the abnormal X chromosome was found to be paternal, whereas the origin of the duplicated part of chromosome 17 was maternal. The unbalanced translocation between the paternal X and the maternal chromosome 17 is, therefore, suggested to be due to a postzygotic error.
Asunto(s)
Anomalías Múltiples/genética , Cromosomas Humanos Par 17 , Monosomía , Translocación Genética , Trisomía , Cromosoma X , Preescolar , Mapeo Cromosómico , Femenino , Marcadores Genéticos , Impresión Genómica , Humanos , Cariotipificación , Masculino , Polimorfismo Genético , Desempeño Psicomotor , CigotoRESUMEN
A boy and his father were found to have very small testes and a fragile site on the long arm of chromosome 16. This fragility would not have been detected in culture medium 199.