Disruption of ST5 is associated with mental-retardation and multiple congenital anomalies

Ina Göhring¹, Andreas Tagariello¹, Sabine Endele¹, Claus C Stolt², Michella Ghassibé³, Malcolm Fisher⁴, Christian T Thiel⁵, Udo Trautmann⁵, Miikka Vikkula³, Andreas Winterpacht⁵, David R FitzPatrick⁴, Anita Rauch^6,*

¹ Institute of Human Genetics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany;
² Institute of Biochemistry, Emil-Fischer Centre, Friedrich-Alexander University Erlangen-Nuremberg, Germany;
³ de Duve Institute, Université catholique de Louvain, Brussels, Germany;
⁴ Medical and Developmental Genetics Section, MRC Human Genetics Unit, Edinburgh, Belgium;
⁵ Institute of Human Genetics, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, United Kingdom;
⁶ Institute of Medical Genetics, University of Zurich, CH-8603 Schwerzenbach-Zurich, Germany

Correspondence to: Anita Rauch, Institute of Medical Genetics, University of Zurich, Schorenstrasse 16, Schwerzenbach, 8603, Switzerland; anita.rauch{at}medgen.uzh.ch

Accepted 10 September 2009

We observed a patient with a cryptic subtelomeric de novo balanced translocation 46,XY.ish t(11;20)(p15.4;q13.2) presenting with severe mental retardation, muscular hypotonia, seizures, bilateral sensorineural hearing loss, submucous cleft palate, persistent ductus Botalli, unilateral cystic kidney dysplasia and frequent infections. Fluorescence in situ hybridization mapping and sequencing of the translocation breakpoints showed that no known genes are disrupted at 20q13.2 and that ST5 (suppression of tumorigenicity 5; MIM 140750 [OMIM] ) is disrupted on 11p15.4. By quantitative PCR from different human tissues we found ST5 relatively evenly expressed in fetal tissues. ST5 expression was more pronounced in adult brain, kidney and muscle than in the corresponding fetal tissues, whereas expression in other tissues was generally lower than in the fetal tissue. Using RNA in situ hybridization in mouse we found that St5 is expressed in the frontal cortex during embryonic development. In adult mouse brain expression of St5 was especially high in the hippocampal area and cerebellum. Hence we suppose that ST5 plays an important role in central nervous system development probably due to disturbance of DENN-domain mediated vesicle formation and neurotransmitter trafficking. Thus, our findings implicate ST5 in the etiology of mental retardation, seizures and multiple congenital anomalies.

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