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Characterization of a new syndrome that associates craniosynostosis, delayed fontanel closure, parietal foramina, imperforate anus, and skin eruption: CDAGS.

ABSTRACT: We describe the clinical characterization, molecular analyses, and genetic mapping of a distinct genetic condition characterized by craniosynostosis, delayed closure of the fontanel, cranial defects, clavicular hypoplasia, anal and genitourinary malformations, and skin eruption. We have identified seven patients with this phenotype in four families from different geographic regions and ethnic backgrounds. This is an autosomal recessive condition that brings together apparently opposing pathophysiologic and developmental processes, including accelerated suture closure and delayed ossification. Selected candidate genes--including RUNX2, CBFB, MSX2, ALX4, TWIST1, and RECQL4--were screened for mutations, by direct sequencing of their coding regions, and for microdeletions, by fluorescent in situ hybridization. No mutations or microdeletions were detected in any of the genes analyzed. A genomewide screen yielded the maximum estimated LOD score of +2.38 for markers D22S283 and D22S274 on chromosome 22q12-q13. We hypothesize that the gene defect in this condition causes novel context-dependent dysregulation of multiple signaling pathways, including RUNX2, during osteoblast differentiation and craniofacial morphogenesis.

SUBMITTER: Mendoza-Londono R

PROVIDER: S-EPMC1226190 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature

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Characterization of a new syndrome that associates craniosynostosis, delayed fontanel closure, parietal foramina, imperforate anus, and skin eruption: CDAGS.

Mendoza-Londono Roberto R Lammer Edward E Watson Rosemarie R Harper John J Hatamochi Atsushi A Hatamochi-Hayashi Saori S Napierala Dobrawa D Hermanns Pia P Collins Sinead S Roa Benjamin B BB Hedge Madhuri R MR Wakui Keiko K Nguyen Diep D Stockton David W DW Lee Brendan B

American journal of human genetics 20050527 1

We describe the clinical characterization, molecular analyses, and genetic mapping of a distinct genetic condition characterized by craniosynostosis, delayed closure of the fontanel, cranial defects, clavicular hypoplasia, anal and genitourinary malformations, and skin eruption. We have identified seven patients with this phenotype in four families from different geographic regions and ethnic backgrounds. This is an autosomal recessive condition that brings together apparently opposing pathophys ...[more]

PMID: 15924278

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Project description:BACKGROUND: The 13q-deletion syndrome causes human congenital birth defects due to the loss of regions of one long arm of human chromosome 13. A distal critical region for severe genitourinary and anorectal birth defects in the region of 13q32.2-34 has been suggested; we sought to narrow this critical region. METHODS: From patients with karyotypes revealing haploinsufficiency for distal chromosome 13q and their parents, peripheral blood was obtained and lymphocytes were immortalized for DNA isolation. Genetic and molecular cytogenetic methods were used to map deletions. Patient and parental samples were genotyped with a panel of 20 microsatellite markers spanning 13q31.3 qter and deletions identified by loss of heterozygosity. Deletions were also mapped using a panel of 35 BAC clones from the same region as probes for fluorescence in-situ hybridization on patient lymphoblastoid metaphase preparations. The data were synthesized and a deletion map defining the critical region was generated. RESULTS: Eight patients with known deletions around 13q32qter and their parents were analyzed, and categorized into three groups: three patients with anorectal and genitourinary anomalies (hypospadias, penoscrotal transposition), four male patients without anorectal and genitourinary anomalies, and one XY patient with ambiguous genitalia without anorectal anomalies. We mapped the critical region for anorectal and genitourinary anomalies to a approximately 9.5-Mb interval of 13q33.3-q34 delineated by markers D13S280-D13S285; this spans approximately 8% of the chromosome and contains 20 annotated genes CONCLUSION: The critical region of chromosome 13q mediating genitourinary/anorectal anomalies has been mapped, and will be narrowed by additional patients and further mapping. Identification of the gene(s) mediating these syndromic genitourinary defects should further our knowledge of molecular mediators of non-syndromic hypospadias, penoscrotal transposition and anorectal malformations.

Dataset Information

Characterization of a new syndrome that associates craniosynostosis, delayed fontanel closure, parietal foramina, imperforate anus, and skin eruption: CDAGS.

Publications

Characterization of a new syndrome that associates craniosynostosis, delayed fontanel closure, parietal foramina, imperforate anus, and skin eruption: CDAGS.

Similar Datasets

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