Genes and chromosomal breakpoints in the Langer-Giedion syndrome region on human chromosome 8

Abstract

The tricho-rhino-phalangeal syndrome type II (TRPS II, or Langer-Giedion syndrome) is an example of contiguous gene syndromes, as it comprises the clinical features of two autosomal dominant diseases, TRPS I and a form of multiple cartilaginous exostoses caused by mutations in the EXT1 gene. We have constructed a contig of cosmid, lambda-phage, PAC, and YAC clones, which covers the entire TRPS I critical region. Using these clones we identified a novel submicroscopic deletion in a TRPS I patient and refined the proximal border of the minimal TRPS1 gene region by precisely mapping the inversion breakpoint of another patient. As a first step towards a complete inventory of genes in the Langer-Giedion syndrome chromosome region (LGCR) with the ultimate aim to identify the TRPS1 gene, we analyzed 23 human expressed sequence tags (ESTs) and four genes (EIF3S3, RAD21, OPG, CXIV) which had been assigned to human 8q24.1. Our analyses indicate that the LGCR is gene-poor, because none of the ESTs and genes map to the minimal TRPS1 gene region and only two of these genes, RAD21 and EIF3S3, are located within the shortest region of deletion overlap of TRPS II patients. Two genes, OPG and CXIV, which are deleted only in some patients with TRPS II may contribute to the clinical variability of this syndrome.

Multiple exostoses, mental retardation, hypertrichosis, and brain abnormalities in a boy with a de novo 8q24 submicroscopic interstitial deletion

“…Primers and conditions were obtained from the genome data base (GDB), PAC7CA is derived from the sequence of PAC7, which maps distal to the TRPS1 gene [Lü decke et al, 1999], and 46F10CA and 65G5CA are EXT1 intragenic markers [Bernard et al, 2001]. The determination of the deletion breakpoint was solely based on the presence or absence of parental alleles, without including results based on band signal intensity.…”

Trichorhinophalangeal Syndrome Type I

“…10,27,28 In our case series, the analysis of the family identified the patient #4 as the first affected individual and was therefore considered de novo (Fig. In 2000, Momeni et al 8 identified the TRPS1 gene, which maps to the long arm of chromosome 8 at 8q24 and encodes a zinc finger transcription factor.…”

“…In the same aminoacid sequence, the mutations C896S/C896F have been identified before 27,30 but the missense mutation c.2726G > A (p.C909Y) has not been identified in a patient with TRPS up to now. The coding region of the TRPS1 gene and flanking intronic regions were amplified by PCR.…”

Síndrome de Langer-Giedion con deleción 8q23.1-q24.12, diagnosticado por hibridación genómica comparativa

“…2 Sin embargo, el LGS presenta un espectro de variabilidad clínica que depende de los genes afectados en la región deletada. 2,6 Otros hallazgos descritos en la literatura incluyen 1 Pese a la variabilidad en el tamaño de la deleción, todos los pacientes con LGS tienen comprometidos los genes EXT1 y TRPS1. 3,7 A continuación, presentamos el reporte de un paciente de origen colombiano con una deleción 8q23.1-q24.12, detectada por hibridación genómica comparativa array (array comparative genomic hybridization; a-CGH, por sus siglas en inglés) en asociación a la presencia de osteocondromas múltiples, y fenotipo facial compatible con LGS.…”