Abstract A recent study suggested that a dodecamer du- plication in exon 42 of the HOPA gene in Xq13 may be a significant factor in the etiology of X-linked mental retar- dation. In an effort to investigate this possibility, we de- termined the incidence of the dodecamer duplication in cohorts of non-fragile X males with mental retardation from three countries, cohorts of fragile X males from two countries, 43 probands from families with X-linked men- tal retardation and control cohorts from three countries. The duplication was found in 3.6–4.0% of male patients from two non-fragile X groups (Italy and South Carolina), in 1.2% from another non-fragile X group (South Africa), but in no male patients from families with X-linked men- tal retardation (South Carolina). The dodecamer duplica- tion was also found in several white males with fragile X syndrome from France (5%) and South Africa (22.2%). Additionally, the duplication was found in 1.5% of South Carolinian newborn males, 2.5% South Carolinian male college students, 5% Italian male controls and 4.5% of the white South African controls. None of the black South African non-fragile X individuals with mental retardation, the fragile X or the control samples tested carried the du- plication, suggesting that the duplication is rare in the black South African population. The incidence of the du- plication was not significantly different between any of the groups in the study. Therefore, results of our studies in four different populations do not corroborate the findings of the previous study, and indicate that the HOPA dode- camer duplication does not convey an increased suscepti- bility to mental retardation. Introduction The preponderance of males among patients with mental retardation (MR) has focused considerable attention on the search for X-linked genes that alter brain structure or function. More than 120 X-linked mental retardation (XLMR) syndromes and 60 families with non-syndromic XLMR have been described (Lubs et al. 1999). Twenty- two genes for syndromic XLMR and four genes for non- syndromic XLMR have been cloned. An additional 53 loci for syndromic XLMR have been regionally mapped and at least 10 non-overlapping linkage regions for non-syn- dromic XLMR have been delineated (Lehrke 1974; Gedeon et al. 1996; Lubs et al. 1999; Stevenson et al. 1999). A 12 bp duplication (CAGCAACACCAG) in a gene located at Xq13 has been implicated as a possible cause of mental retardation in males (Philibert et al. 1998a; Philibert et al. 1998b). The duplication was identified while sequenc- ing fragments of genomic DNA containing large trinu- cleotide repeats. The gene contains a CAG-rich opa repeat sequence and has been named the human opposite paired (HOPA) gene (GenBank accession no. AF071309). When three cohorts of non-fragile X males with mental retardation (NFXMR) males were screened, it was found that 3.7%, 7.3%, and 14% of patients had the dodecamer duplication in exon 42 of the HOPA gene (Philibert et al. 1998b). The frequency of the duplication in the first two cohorts was shown to be significantly higher than in the control groups. The function of the HOPA gene is unknown. It is ex- pressed in a number of tissues including brain (Philibert et Michael J. Friez · Fahmida B. Essop · Amanda Krause · Lucia Castiglia · Angela Ragusa · Khalid Sossey-Alaoui · Retecher L. Nelson · Melanie M. May · Ron C. Michaelis · Anand K. Srivastava · Charles E. Schwartz · Roger E. Stevenson · Andrea Goldman · Laurent Villard · John W. Longshore Evidence that a dodecamer duplication in the gene HOPA in Xq13 is not associated with mental retardation Hum Genet (2000) 106 : 36–39 Digital Object Identifier (DOI) 10.1007/s004399900202 Received: 1 October 1999 / Accepted: 4 November 1999 / Published online: 4 December 1999 ORIGINAL INVESTIGATION M. J. Friez · K. Sossey-Alaoui · R. L. Nelson · M. M. May · R. C. Michaelis · A. K. Srivastava · C. E. Schwartz · R. E. Stevenson · J. W. Longshore (✉) Greenwood Genetic Center, Greenwood, South Carolina, 29646, USA e-mail: john@ggc.org, Tel.: +1-864-9418130, Fax: +1-864-9418133 F.B. Essop · A. Krause · A. Goldman Department of Human Genetics, School of Pathology, The South African Institute for Medical Research and the University of the Witwatersand, P.O. Box 1038, Johannesburg, 2000, South Africa L. Castiglia · A. Ragusa Laboratorio di Patologia Genetica, Istituto Oasi (I.R.C.C.S.), Troina, Italy L. Villard (✉) INSERM U491, Faculté de Médecine La Timone, Marseille, France e-mail: villard@medecine.univ-mrs.fr, Tel.: +33-4-91784477, Fax: +33-4-91804319 © Springer-Verlag 1999