A newly defined X linked mental retardation syndrome associated with alpha thalassaemia.

In 1981 three northern European families were described in which a severely mentally retarded son also had haemoglobin H (Hb H) disease.' These findings were of interest because Hb H disease, a relatively severe manifestation of a thalassaemia, is rare in northern Europeans although it is frequently seen in Mediterranean and Oriental racial groups in which it is not known to be associated with an increased frequency of mental retardation. Furthermore, whereas the common forms of Hb H disease are always inherited in a mendelian fashion, in these northern European families this appeared not to be so. Hb H disease occurs when a greater than 50% reduction in synthesis of the a globin chains of adult haemoglobin (Hb A, a212) results in the accumulation of excess 1 globin chains which form 14 tetramers (Hb H). The common mendelian forms of HbH disease result from mutations of both allelic a globin complexes, most commonly owing to deletions or less frequently to small rearrangements or point mutations. The a globin complex is located close to the telomere of the short arm of chromosome 16, within band 16pl3.3. By 1990, a total of 13 subjects with a thalassaemia and mental retardation (ATR) had been identified and two distinct syndromes were delineated.34 Eight patients had large (1 to 2 megabases) deletions of the tip of chromosome 16p; the clinical features of this so called ATR-16 syndrome were rather variable, in