BRACHYDACTYLY AND MENTAL-RETARDATION - AN ALBRIGHT HEREDITARY OSTEODYSTROPHY-LIKE SYNDROME LOCALIZED TO 2Q37

We report five patients with a combination of brachymetaphalangia and mental retardation, similar to that observed in Albright hereditary os teodystrophy (AHO). Four patients had cytogenetically visible de novo deletions of chromosome 2q37. The fifth patient was cytogenetically no rmal and had normal bioactivity of the alpha subunit of Gs (Gs alpha), the protein that is defective in AHO. In this patient, we have used a combination of highly polymorphic molecular markers and FISH to demon strate a microdeletion at 2q37. The common region of deletion overlap involves the most telomeric 2q marker, D2S125, and extends proximally for a maximum distance of 17.6 cM. We suggest this represents a consis tent phenotype associated with some deletions at 2q37 and that genes i mportant for skeletal and neurodevelopment lie within this region. Scr eening for deletions at this locus should be considered in individuals with brachymetaphalangia and mental retardation. Furthermore, 2q37 re presents a candidate region for type E brachydactyly.