The original Lujan Syndrome Family has a novel missense mutation (p.N1007S) in the MED12 gene

Charles E. Schwartz ¹, Patrick S Tarpey ², Herbert A Lubs ³, Alain Verloes ⁴, Melanie M May ³, Hiba Risheg ³, Michael J Friez ³, P Andrew Futreal ⁵, Sarah Edkins ⁶, Jon W Teague ⁶, Sylvain Briault ⁷, Cindy Skinner ³, Astrid Bauer-Carlin ³, Richard J Simensen ³, Sumy M Joseph ³, Julie R Jones ³, Jozef Gecz ⁸, Michael R Stratton ⁹, F Lucy Raymond ¹⁰ and Roger E Stevenson ^3*

¹ JC Self Research Institute, United States
² Wellcome Trust Sanger Institute, United Kingdom
³ Greenwood Genetic Center, United States
⁴ Robert Debre University Hospital, France
⁵ Wellcome Trust Sanger Institute, United States
⁶ Wellcome Trust Sanger Institute, France
⁷ Centre Hospilalier Regional d'Orleans, France
⁸ Women and Children's Hospital, University of Adelaide, Australia
⁹ Sanger Institute, United Kingdom
¹⁰ University of Cambridge, United Kingdom

^* To whom correspondence should be addressed. E-mail: res{at}ggc.org.

Accepted 27 February 2007

Abstract

A novel missense mutation in the Mediator of RNA Polymerase II Transcription Subunit 12 gene, MED12, has been found in the original family with Lujan syndrome and in a second family (K9359) that was initially considered to have Opitz-Kaveggia (FG) syndrome. A different missense mutation in MED12 has been previously reported in the original family with Opitz-Kaveggia syndrome and in five other families with compatible clinical findings. Neither sequence alteration has been found in over 1,400 control X chromosomes. Lujan (Lujan-Fryns) syndrome is characterized by tall stature with asthenic habitus, macrocephaly, tall narrow face, maxillary hypoplasia, high narrow palate with dental crowding, small or receding chin, long hands with hyperextensible digits, hypernasal speech, hypotonia, mild to moderate mental retardation, behavioral aberrations and dysgenesis of the corpus callosum. Although Lujan syndrome has not been previously considered to be in the differential diagnosis of Opitz-Kaveggia syndrome, there are some overlapping clinical manifestations, specifically dysgenesis of the corpus callosum, macrocephaly/relative macrocephaly, tall forehead, hypotonia, mental retardation and behavioral disturbances. Thus it appears that these two XLMR syndromes are allelic, having mutations in the MED12 gene.

Keywords: FG syndrome, Lujan syndrome, Lujan-Fryns syndrome, MED12, X-linked mental retardation with Marfanoid habitus

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