ABSTRACT
The chromosome 1q21.1 duplication syndrome (OMIM# 612475) is characterized by head anomalies, mild facial dysmorphisms, and cognitive problems, including autistic features, mental retardation, developmental delay, and learning disabilities. Speech and language development are sometimes impaired, but no detailed characterization of language problems in this condition has been provided to date. We report in detail on the cognitive and language phenotype of a child who presents with a duplication in 1q21.1 (arr[hg19] 1q21.1q21.2(145,764,455-147,824,207) × 3), and who exhibits cognitive delay and behavioral disturbances. Language is significantly perturbed, being the expressive domain the most impaired area (with significant dysphemic features in absence of pure motor speech deficits), although language comprehension and use (pragmatics) are also affected. Among the genes found duplicated in the child, CDH1L is upregulated in the blood of the proband. ROBO1, a candidate for dyslexia, is also highly upregulated, whereas, TLE3, a target of FOXP2, is significantly downregulated. These changes might explain language, and particularly speech dysfunction in the proband.
ABSTRACT
The 15q11.2 BP1-BP2 region is found duplicated or deleted in people with cognitive, language, and behavioral impairment. We report on a family (a father and 3 male twin siblings) that presents with a duplication of the 15q11.2 BP1-BP2 region and a variable phenotype: the father and the fraternal twin are normal carriers, whereas the monozygotic twins exhibit severe language and cognitive delay as well as behavioral disturbances. The genes located within the duplicated region are involved in brain development and function, and some of them are related to language processing. The probands' phenotype may result from changes in the expression level of some of these genes important for cognitive development.
ABSTRACT
We report on a girl who presents with hearing loss, behavioral disturbances (according to the Inventory for Client and Agency Planning) as well as motor and cognitive delay (according to Battelle Developmental Inventories) which have a significant impact on her speech and language abilities [according to the Peabody Picture Vocabulary Test (ed 3), and the Prueba de Lenguaje Oral de Navarra-Revisada (Navarra Oral Language Test, Revised)]. Five copy number variations (CNVs) were identified in the child: arr[hg18] 7q32.1q33(127109685-132492196)×1, 8p23.1(7156900-7359099) ×1, 15q13.1(26215673-26884937)×1, Xp22.33(17245- 102434)×3, and Xp22.33(964441-965024)×3. The pathogenicity of similar CNVs is mostly reported as unknown. The largest deletion is found in a hot spot for cognitive disease and language impairment and contains several genes involved in brain development and function, many of which have been related to developmental disorders encompassing language deficits (dyslexia, speech-sound disorder, and autism). Some of these genes interact with FOXP2. The proband's phenotype may result from a reduced expression of some of these genes.
ABSTRACT
Introducción. En los últimos años la aplicación de la hibridación in situ fluorescente (FISH) permite el diagnóstico precoz de aneuploidias. El objetivo de este estudio es el análisis descriptivo mediante FISH de los líquidos amnióticos procesados en el laboratorio y la concordancia con el cariotipo. Material y métodos. Análisis de 821 muestras de líquidos amnióticos (enero 2009 a diciembre 2010) remitidas por Medicina Fetal desde la semana 13 a 36 de gestación para estudio prenatal de aneuploidias, (kit Aneuvysion) con sondas centroméricas para los cromosomas X, Y y 18, y locus específicas para los cromosomas 13 y 21. El estudio se completa con el cariotipo mediante método de bandeo G. Resultados. De las 821 muestras, 776 (94,52%) fueron normales y 45 (5,48%) presentaron aneuploidias: en 22 casos (48,88%) el sexo cromosómico del feto fue masculino, en las 23 restantes (51,12%) femenino. La cromosopatía más frecuente fue la trisomía 21 (19 casos en fetos masculinos y 11 femeninos), la de menor presentación fue la trisomía 13 (2 casos) que representa el 0,24% del total de los líquidos amnióticos procesados. En todos los casos, la concordancia con el cariotipo fue del 100%. Conclusiones. El estudio de aneuploidias mediante FISH en núcleos en interfase en líquido amniótico permite un diagnóstico prenatal rápido de las principales cromosomopatías, siendo la trisomía 21 la más frecuentemente detectada. Los resultados del FISH coincidieron en el 100% con el cariotipo, gold estándar en el diagnóstico prenatal de cromosomopatías (AU)
Background. The application of fluorescence in situ hybridization (FISH) techniques in the last few years has led to the prenatal diagnosis of aneuploidies. The objective of this investigation was a descriptive analysis of amniotic fluids processed in the laboratory using FISH and the agreement with the karyotype. Material and methods. A total of 821 amniotic fluid samples (January 2009 to December 2010) at gestational ages 13 to 36 weeks, from Fetal Medicine Unit for prenatal testing for aneuploidies (Aneuvysion kit) with centromeric probes for chromosomes X,Y and 18, and locus specific for chromosomes 13 and 21. The study was complemented by the karyotype by G-banding method. Results. Of the 821 samples, 776 (94.52%) were normal and 45 (5.48%) had aneuploidy: in 22 cases (48.88%) the chromosomal sex of the foetus was male, in the remaining 23 (51.12%) female. The most common chromosomal abnormality detected was trisomy 21 (19 cases in males and 11 cases in female foetuses), the lowest performance was the trisomy 13 (2 cases) representing 0.24% of total processed amniotic fluids. In all cases, the concordance with the karyotype was 100%. Conclusions. The study of aneuploidy by FISH of interphase nuclei present in the amniotic fluid enables rapid prenatal diagnosis of major chromosomal abnormalities, trisomy 21 was more frequently detected. FISH results in 100% agreed with the karyotype, the gold standard in prenatal diagnosis of chromosomal abnormalities (AU)
