RESUMO
In a sporadic case of autism and language deficit due to auditory processing defects, molecular genetic studies revealed that a chromosomal deletion occurred in the 13q12-->q13 region. No chromosome abnormalities were detected in the parents. We determined that the deletion occurred on the paternally derived chromosome 13. There are two previous reports of chromosome 13 abnormalities in patients with autism. The deletion in the subject described in this paper maps between the two chromosome 13 linkage peaks described by Bradford et al. (2001) in studies of subjects with autism and language deficits. The 9-Mb region deleted in the patient described here contains at least four genes that are expressed in brain and that play a role in brain development. They are NBEA, MAB21L1, DCAMKL1 and MADH9. These genes therefore represent candidate genes for autism and specific language deficits.
Assuntos
Transtorno Autístico/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 13 , Transtornos da Audição/genética , Percepção da Fala , Pré-Escolar , Mapeamento Cromossômico , Ligação Genética , Humanos , Hibridização in Situ Fluorescente , Transtornos da Linguagem/genética , MasculinoRESUMO
We recently studied a patient who meets criteria for autistic disorder and has a 2q37 deletion. Molecular cytogenetic studies were carried out using DNA isolated from 22 different 2q37 mapped BACs to more precisely define the extent of the chromosome deletion. We also analyzed 2q37 mapped polymorphic markers. In addition DNA sequences of BACs in the deletion region were scanned to identify microsatellite repeats. We describe four new polymorphic microsatellite repeat markers in the 2q37.3 region. These markers enabled us to determine the parental origin of the deletion in our patient. DNA from 8-13 unrelated individuals was used to determine heterozygosity estimates for these markers. We review four genes deleted in our patient - genes whose known functions and sites of expression in the brain and/or bone make them candidates for involvement in autism and/or the osteodystrophy observed in patients with 2q37.3 deletions.
Assuntos
Transtorno Autístico/complicações , Transtorno Autístico/genética , Doenças Ósseas/complicações , Doenças Ósseas/genética , Deleção Cromossômica , Cromossomos Humanos Par 2/genética , Adolescente , Adulto , Transtorno Autístico/fisiopatologia , Osso e Ossos/metabolismo , Encéfalo/metabolismo , Criança , Pré-Escolar , Cromossomos Artificiais Bacterianos , Mapeamento de Sequências Contíguas , Sondas de DNA , Feminino , Deleção de Genes , Marcadores Genéticos/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Repetições de Microssatélites/genética , Polimorfismo Genético/genética , PsicometriaRESUMO
Fluorescent in situ hybridization (FISH) identified a cryptic balanced reciprocal translocation in the mother of an infant with the cri-duchat syndrome. A biotinylated probe from a flow-sorted chromosome 5 cosmid library was used to show the distal deletion of 5p15.2 in the propositus and a translocation of this segment to the distal end of 7 at 7p21 in his mother. In a subsequent pregnancy, the fetus was shown to have normal chromosomes using the same 5 cosmid library probe and a locus-specific probe derived from the 5p15.3 region. The importance of incorporating FISH into the routine diagnostic laboratory is discussed.
Assuntos
Cromossomos Humanos Par 5 , Cromossomos Humanos Par 7 , Síndrome de Cri-du-Chat/genética , Translocação Genética , Adulto , Amniocentese , Bandeamento Cromossômico , Cosmídeos , Síndrome de Cri-du-Chat/diagnóstico , Sondas de DNA , Feminino , Biblioteca Gênica , Humanos , Hibridização in Situ Fluorescente , Técnicas In Vitro , Recém-Nascido , Cariotipagem , GravidezRESUMO
McKusick-Kaufman syndrome is an autosomal recessive multiple malformation syndrome characterized by hydrometrocolpos and polydactyly. We report on a patient with McKusick-Kaufman syndrome and severe hydrops. This case illustrates the necessity of genetic evaluations for all patients with unexplained hydrops.
Assuntos
Anormalidades Múltiplas , Hidropisia Fetal/complicações , Anormalidades Urogenitais , Doenças Uterinas/complicações , Feminino , Genes Recessivos , Humanos , Recém-Nascido , Deformidades Congênitas dos Membros , SíndromeRESUMO
In cases of fetal neural tube defects (NTD), termination of pregnancy without ascertainment of specific etiology may lead to provision of incorrect recurrence risks and erroneous diagnosis in future pregnancies. Four patients are presented who illustrate the etiologic diversity of neural tube defects. The patients were referred for prenatal diagnosis because of elevated maternal serum alphafetoprotein (AFP). All four chose pregnancy termination. Diagnostic methods included fetal ultrasound, amniocentesis for fetal karyotyping and amniotic fluid AFP/acetylcholinesterase (AChE) and/or fetal karyotyping after delivery, and dysmorphology evaluation of the fetus after intact delivery. These cases highlight the benefits of fetal karyotype analysis and of an intact delivery and thorough clinical examination of the fetus when patients choose to terminate pregnancies with fetal anomalies.
