Dataset Information

Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency.

ABSTRACT:

Purpose

Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved.

Methods

Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types ofSOX5 alterations. Functional consequences of selected substitutions were investigated.

Results

Microdeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated.

Conclusions

This study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features.

SUBMITTER: Zawerton A

PROVIDER: S-EPMC9063678 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency.

Zawerton Ash A Mignot Cyril C Sigafoos Ashley A Blackburn Patrick R PR Haseeb Abdul A McWalter Kirsty K Ichikawa Shoji S Nava Caroline C Keren Boris B Charles Perrine P Marey Isabelle I Tabet Anne-Claude AC Levy Jonathan J Perrin Laurence L Hartmann Andreas A Lesca Gaetan G Schluth-Bolard Caroline C Monin Pauline P Dupuis-Girod Sophie S Guillen Sacoto Maria J MJ Schnur Rhonda E RE Zhu Zehua Z Poisson Alice A El Chehadeh Salima S Alembik Yves Y Bruel Ange-Line AL Lehalle Daphné D Nambot Sophie S Moutton Sébastien S Odent Sylvie S Jaillard Sylvie S Dubourg Christèle C Hilhorst-Hofstee Yvonne Y Barbaro-Dieber Tina T Ortega Lucia L Bhoj Elizabeth J EJ Masser-Frye Diane D Bird Lynne M LM Lindstrom Kristin K Ramsey Keri M KM Narayanan Vinodh V Fassi Emily E Willing Marcia M Cole Trevor T Salter Claire G CG Akilapa Rhoda R Vandersteen Anthony A Canham Natalie N Rump Patrick P Gerkes Erica H EH Klein Wassink-Ruiter Jolien S JS Bijlsma Emilia E Hoffer Mariëtte J V MJV Vargas Marcelo M Wojcik Antonina A Cherik Florian F Francannet Christine C Rosenfeld Jill A JA Machol Keren K Scott Daryl A DA Bacino Carlos A CA Wang Xia X Clark Gary D GD Bertoli Marta M Zwolinski Simon S Thomas Rhys H RH Akay Ela E Chang Richard C RC Bressi Rebekah R Sanchez Russo Rossana R Srour Myriam M Russell Laura L Goyette Anne-Marie E AE Dupuis Lucie L Mendoza-Londono Roberto R Karimov Catherine C Joseph Maries M Nizon Mathilde M Cogné Benjamin B Kuechler Alma A Piton Amélie A Klee Eric W EW Lefebvre Véronique V Clark Karl J KJ Depienne Christel C

Genetics in medicine : official journal of the American College of Medical Genetics 20191003 3

<h4>Purpose</h4>Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pa ...[more]

PMID: 31578471

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Dataset Information

Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency.

Purpose

Methods

Results

Conclusions

Publications

Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency.

Similar Datasets

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