Huntington's disease in Saudi Arabia.

We read with interest the letter by Scrimgeour et al' in the November issue of this Journal. Our hospital, King Faisal Specialist Hospital and Research Centre, is the major re-ferral centre for tertiary care in this country and, over a period of six years, four native Saudi families have been diagnosed with Huntington's disease at our hospital. One of these families (family 1) was described by Scrimgeour et al' in their letter. The second family lives in Qatif, an old city on the Arabian Gulf. Members of the third family live in the mid-northern area of the Arabian peninsula and are of Bedouin (nomad) origin, while the fourth family live in Qassim, the central part of the peninsula. The inheritance is clearly autosomal dominant in all. The disease starts around early adult life with mood and personality changes, clumsiness, and chorea. Brain MRI scan confirmed striking caudate atrophy with increased bicaudate diameter. All metabolic and haematological tests were normal. Apart from a maternal grandfather from family 1 who married into a Moroccan family, there were no known foreign antecedents. Analysis of the trinucleotide repeat in the Huntington gene IT15 (4p16.3) by means of PCR confirmed the presence of an expanded repeat in members of families 2, 3, and 4. The findings in family 2 were included in the world wide study of the Huntington's disease mutation' organised by Dr Hayden's group. A DNA study in the third and fourth families was done with the help of the were found in all affected patients within a range of 42 to 50. Similar findings were seen among other Huntington's disease cases from different nations and ethnic groups.2" As indicated in these reports, CAG expansion is highly specific for Huntington's disease and is not seen in other neuropsychiatric disorders with which Huntington's disease can be confused clinically. While the comment of Scrimgeour et al' that the disease gene was transmitted to the Saudi families by Europeans visiting the Red Sea or the Arabian Gulf may be true, we think this is unlikely. Such ethnic intermixing could not be substantiated in our cases; we think this is particularly unlikely in native nomads. Marriage outside the tribe is a very uncommon practice. It is more likely that a fresh mutation accounted for Huntington's disease in these families. The new mutation rate in Huntington's disease, previously deemed to be exceedingly rare, is now known to be …