SOX11-related syndrome: report on a new case and review

Abstract

The SOX11 gene is a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate.Recently, SOX11 variants were linked to cases of overlapping syndromes collectively termed SSRIDDs, which are mainly associated with variants in BAF complex genes. Patients with these various syndromes exhibit a spectrum of features including developmental delay, intellectual disability, feeding difficulties, hypotonia, short stature, microcephaly, fifth finger hypoplasia, behavioural problems and seizures. We report a novel de novo mutation in SOX11, c.146T>A [p.Ile49Asn], found by exome sequencing in a middle eastern child with intellectual deficiency, developmental delay, microcephaly, thick scalp hairs, long eyelashes and eyebrows, and low-set ears. No abnormalities of fingers were noted. The SOX11-related SSRIDD and a review of SOX11 reported cases are discussed.

SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile

“…We confirm that ocular malformations-coloboma, lens abnormalities, and microphthalmia-occur in SOX11 syndrome. [24][25][26][27] These are recapitulated in sox11 null zebrafish, confirming the specificity of the finding. 28 In our cohort, 10% of patients had oculomotor apraxia.…”

“…Centre, London Health Sciences Foundation, London Health Sciences Centre, London, Ontario, Canada; 4 Biosciences Institute, Newcastle University, Newcastle Upon Tyne, United Kingdom; 5 Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; 6 16 Ambulanzzentrum UKSH, Institut für Humangenetik, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; 17 Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India; 18 Medical Genetics Laboratory, Bambino Gesu Children's Hospital, Rome, Italy; 19 Paediatric Department, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; 20 Angers University Hospital Center, Angers, France; 21 Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; 22 Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 23 EA7364 RADEME, Institute of Medical Genetics, Lille University Hospital, Lille University, Lille, France; 24 Faculty of Nutritional Science, Sagami Women's University, Sagamihara, Japan; 25 Department of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan; 26 Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan; 27 Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan; 28 Department of Orthopedic Surgery, Keio University School of Medicine, Keio University, Tokyo, Japan; 29 Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium; 30…”

Consolidation of the clinical and genetic definition of aSOX4-related neurodevelopmental syndrome

“…SOX4 and SOX11 (SOXC) heterozygous variants have been described in patients with neurodevelopmental syndromes, mild dysmorphisms and various other inconstant anomalies 9–17. The two disease phenotypes are similar, an observation consistent with findings in animal models that SOX4 and SOX11 are co-expressed in various progenitor cell types and have additive or redundant roles in many developing organs, including the brain, skeleton, heart and eye 18–24.…”

Catalogue for Transmission Genetics in Arabs (CTGA) Database: Analysing Lebanese Data on Genetic Disorders

“…Almost all of these are syndromic conditions, with a combination of clinical features not described elsewhere. For instance, variants of MCA/MR (multiple congenital anomalies/mental retardation) conditions with new constellations of features [14,15], novel phenotypes associated with genes known to cause other related genetic diseases [16,17], and other syndromic congenital disorders [18,19]. The absence of these disorders in other genetic databases like OMIM points to the rarity of these conditions.…”