Dataset Information

The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP.

ABSTRACT: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.

SUBMITTER: Nikkel SM

PROVIDER: S-EPMC3659005 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP.

Nikkel Sarah M SM Dauber Andrew A de Munnik Sonja S Connolly Meghan M Hood Rebecca L RL Caluseriu Oana O Hurst Jane J Kini Usha U Nowaczyk Malgorzata J M MJ Afenjar Alexandra A Albrecht Beate B Allanson Judith E JE Balestri Paolo P Ben-Omran Tawfeg T Brancati Francesco F Cordeiro Isabel I da Cunha Bruna Santos BS Delaney Louisa A LA Destrée Anne A Fitzpatrick David D Forzano Francesca F Ghali Neeti N Gillies Greta G Harwood Katerina K Hendriks Yvonne M C YM Héron Delphine D Hoischen Alexander A Honey Engela Magdalena EM Hoefsloot Lies H LH Ibrahim Jennifer J Jacob Claire M CM Kant Sarina G SG Kim Chong Ae CA Kirk Edwin P EP Knoers Nine V A M NV Lacombe Didier D Lee Chung C Lo Ivan F M IF Lucas Luiza S LS Mari Francesca F Mericq Veronica V Moilanen Jukka S JS Møller Sanne Traasdahl ST Moortgat Stephanie S Pilz Daniela T DT Pope Kate K Price Susan S Renieri Alessandra A Sá Joaquim J Schoots Jeroen J Silveira Elizabeth L EL Simon Marleen E H ME Slavotinek Anne A Temple I Karen IK van der Burgt Ineke I de Vries Bert B A BB Weisfeld-Adams James D JD Whiteford Margo L ML Wierczorek Dagmar D Wit Jan M JM Yee Connie Fung On CF Beaulieu Chandree L CL White Sue M SM Bulman Dennis E DE Bongers Ernie E Brunner Han H Feingold Murray M Boycott Kym M KM

Orphanet journal of rare diseases 20130427

<h4>Background</h4>Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.<h4>Methods and results</h4>Clinical information on fifty-two individuals with SRCAP mutations was collected using stand ...[more]

PMID: 23621943

Similar Datasets

Project description:BackgroundA variety of human genetic diseases is known to be caused by mutations in genes encoding chromatin factors and epigenetic regulators, such as DNA or histone modifying enzymes and members of ATP-dependent chromatin remodeling complexes. Floating-Harbor syndrome is a rare genetic disease affecting human development caused by dominant truncating mutations in the SRCAP gene, which encodes the ATPase SRCAP, the core catalytic subunit of the homonymous chromatin-remodeling complex. The main function of the SRCAP complex is to promote the exchange of histone H2A with the H2A.Z variant. According to the canonical role played by the SRCAP protein in epigenetic regulation, the Floating-Harbor syndrome is thought to be a consequence of chromatin perturbations. However, additional potential physiological functions of SRCAP have not been sufficiently explored.ResultsWe combined cell biology, reverse genetics, and biochemical approaches to study the subcellular localization of the SRCAP protein and assess its involvement in cell cycle progression in HeLa cells. Surprisingly, we found that SRCAP associates with components of the mitotic apparatus (centrosomes, spindle, midbody), interacts with a plethora of cytokinesis regulators, and positively regulates their recruitment to the midbody. Remarkably, SRCAP depletion perturbs both mitosis and cytokinesis. Similarly, DOM-A, the functional SRCAP orthologue in Drosophila melanogaster, is found at centrosomes and the midbody in Drosophila cells, and its depletion similarly affects both mitosis and cytokinesis.ConclusionsOur findings provide first evidence suggesting that SRCAP plays previously undetected and evolutionarily conserved roles in cell division, independent of its functions in chromatin regulation. SRCAP may participate in two different steps of cell division: by ensuring proper chromosome segregation during mitosis and midbody function during cytokinesis. Moreover, our findings emphasize a surprising scenario whereby alterations in cell division produced by SRCAP mutations may contribute to the onset of Floating-Harbor syndrome.

Dataset Information

The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP.

Publications

The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure