American Journal of Medical Genetics 122A:261–265 (2003) Clinical Report Narrowing the Candidate Region of Albright Hereditary Osteodystrophy-Like Syndrome by Deletion Mapping in a Patient With an Unbalanced Cryptic Translocation t(2;6)(q37.3;q26) Daniela Giardino, 1 * Palma Finelli, 1,2 Giulietta Gottardi, 1 Gabriella De Canal, 1 Matteo Della Monica, 3 Fortunato Lonardo, 3 Gioacchino Scarano, 3 and Lidia Larizza 1,2 1 Laboratorio di Citogenetica, Istituto Auxologico Italiano, Milan, Italy 2 Dipartimento di Biologia e Genetica, Universita ` degli Studi, Milan, Italy 3 U.O.C. di Genetica Medica, Osp. G. Rummo, Benevento, Italy We here describe a submicroscopic translo- cation affecting the subtelomeric regions of chromosomes 2q and 6q identified in a patient referred to us because of mental retardation, obesity, brachydactyly, and short stature. FISH analysis using subtelo- meric probes showed a 46,XY,der(2)t(2;6) (q37.3;q26) in the propositus, and a balanced t(2;6) in his father and sister. FISH with region-specific genomic clones made it pos- sible to map the 2q37.3 breakpoint precisely to the region covered by BAC 585E12, and the 6q26 breakpoint to between the regions encompassed by 414A5 and 480A20. The 2q subtelomeric deletion has often been found in patients with Albright hereditary osteo- dystrophy (AHO)-like syndrome but, to the best of our knowledge, the 2q37.3-qter mono- somy ascertained in our patient is the smal- lest so far described within the syndrome’s critical interval, and may thus enhance the search for the responsible genes. ß 2003 Wiley-Liss, Inc. KEY WORDS: 2qter deletion; AHO-like syndrome; candidate gene region; 6q partial trisomy INTRODUCTION There have been a number of reports concerning patients with a 2q37 deletion who present with Albright hereditary osteodystrophy (AHO)-like syndrome, also called brachydactyly-mental retardation syndrome (OMIM 600430) [Phelan et al., 1995; Wilson et al., 1995; Power et al., 1997; Voit-Szoboszlai et al., 1998; Bijlsma et al., 1999; Reddy et al., 1999]. The critical region of the gene(s) responsible for the characteristic features of this syndrome has been identified as 2q37.3- qter [Phelan et al., 1995], and narrowed to the interval delimited by the centromeric marker D2S338 [Wilson et al., 1995]; the critical region for the skeletal mal- formations associated with AHO-like syndrome has been restricted to 10 cM (5 Mb) from D2S338 to D2S125 [Bonaglia et al., 2000]. It has been shown that 2q is frequently involved in the cryptic familial sub- telomeric rearrangements associated with syndromic mental retardation [Bijlsma et al., 1999; Bacino et al., 2000; Speleman et al., 2000; Giardino et al., 2001], and a recent clinical report has proposed the Glypican 1 gene as a candidate for brachydactyly, one of the major characteristics of the AHO-like phenotype [Syrrou et al., 2002]. Other likely candidates include the vasoactive intestinal peptide receptor (RDCI) gene [Power et al., 1997] and the STK25 gene, which has been mapped to 2q37 by syntenic homology. We here report the results of clinical and genetic studies of a patient carrying a terminal 2q deletion and 6q duplication due to the malsegregation of a paternal balanced translocation. Precise FISH mapping of the 2q deletion centromeric boundary made it possible to restrict it to the minimal deletion region for AHO-like syndrome. Comparison of the patient’s clinical descrip- tion with those of the other reported cases of 2q37- deleted AHO-like syndrome may help to clarify the spectrum of the AHO-like phenotype and identify the candidate gene(s). Grant sponsor: Italian Ministry of Health (to Istituto Auxolo- gico Italiano); Grant number: 030.11/RF00.133. *Correspondence to: Dr. Daniela Giardino, Ph.D., Lab. Cito- genetica Medica, Istituto Auxologico Italiano, Via Ariosto 13, 20145 Milano, Italy. E-mail: giardino@auxologico.it Received 4 November 2002; Accepted 24 March 2003 DOI 10.1002/ajmg.a.20287 ß 2003 Wiley-Liss, Inc.