Dataset Information

A gene for isolated congenital ptosis maps to a 3-cM region within 1p32-p34.1.

ABSTRACT: Hereditary isolated congenital ptosis is an autosomal dominant disorder with incomplete penetrance characterized by a variable degree of unilateral or bilateral drooping of the upper eyelids. We report linkage of this disorder in a large family to markers on chromosome 1p. In our sample of 37 meioses, nine informative markers did not recombine with the disease. D1S2677 gave a maximum two-point LOD score of 8.8 on the assumption of 90% penetrance (theta = 0). D1S447/2733 and D1S1616 flank the disease locus, with two-point LOD scores of 5.6/6.6 (theta = .04) and 4.9 (theta = .05), respectively, defining a region of 2.8 cM. FISH of YACs containing flanking recombinant markers localizes the gene to chromosome 1p32-p34.1. These data establish a map location for an isolated congenital ptosis gene and demonstrate that this disorder is genetically distinct from other extraocular muscle-specific disorders such as congenital fibrosis of the extraocular muscles and blepharophimosis.

SUBMITTER: Engle EC

PROVIDER: S-EPMC1712439 | biostudies-other | 1997 May

REPOSITORIES: biostudies-other

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A gene for isolated congenital ptosis maps to a 3-cM region within 1p32-p34.1.

Engle E C EC Castro A E AE Macy M E ME Knoll J H JH Beggs A H AH

American journal of human genetics 19970501 5

Hereditary isolated congenital ptosis is an autosomal dominant disorder with incomplete penetrance characterized by a variable degree of unilateral or bilateral drooping of the upper eyelids. We report linkage of this disorder in a large family to markers on chromosome 1p. In our sample of 37 meioses, nine informative markers did not recombine with the disease. D1S2677 gave a maximum two-point LOD score of 8.8 on the assumption of 90% penetrance (theta = 0). D1S447/2733 and D1S1616 flank the dis ...[more]

PMID: 9150162

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Project description:BackgroundRecurrent loss of part of the long arm of chromosome 11 is a well established hallmark of a subtype of aggressive neuroblastomas. Despite intensive mapping efforts to localize the culprit 11q tumour suppressor gene, this search has been unsuccessful thus far as no sufficiently small critical region could be delineated for selection of candidate genes.MethodsTo refine the critical region of 11q loss, the chromosome 11 status of 100 primary neuroblastoma tumours and 29 cell lines was analyzed using a BAC array containing a chromosome 11 tiling path. For the genes mapping within our refined region of loss, meta-analysis on published neuroblastoma mRNA gene expression datasets was performed for candidate gene selection. The DNA methylation status of the resulting candidate gene was determined using re-expression experiments by treatment of neuroblastoma cells with the demethylating agent 5-aza-2'-deoxycytidine and bisulphite sequencing.ResultsTwo small critical regions of loss within 11q23 at chromosomal band 11q23.1-q23.2 (1.79 Mb) and 11q23.2-q23.3 (3.72 Mb) were identified. In a first step towards further selection of candidate neuroblastoma tumour suppressor genes, we performed a meta-analysis on published expression profiles of 692 neuroblastoma tumours. Integration of the resulting candidate gene list with expression data of neuroblastoma progenitor cells pinpointed CADM1 as a compelling candidate gene. Meta-analysis indicated that CADM1 expression has prognostic significance and differential expression for the gene was noted in unfavourable neuroblastoma versus normal neuroblasts. Methylation analysis provided no evidence for a two-hit mechanism in 11q deleted cell lines.ConclusionOur study puts CADM1 forward as a strong candidate neuroblastoma suppressor gene. Further functional studies are warranted to elucidate the role of CADM1 in neuroblastoma development and to investigate the possibility of CADM1 haploinsufficiency in neuroblastoma.

Dataset Information

A gene for isolated congenital ptosis maps to a 3-cM region within 1p32-p34.1.

Publications

A gene for isolated congenital ptosis maps to a 3-cM region within 1p32-p34.1.

Similar Datasets

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