Neural tube defects and the 13q deletion syndrome: Evidence for a criticalregion in 13q33-34

Neural tube defects (NTD) are common findings in the 13q deletion syndrome, but the relationship between the 13q- syndrome and NTDs is poorly understo od. We present a child with a 13q deletion and lumbosacral myelomeningocele , This was a boy with microcephaly, telecanthus, minor facial anomalies, an d ambiguous genitalia. Cytogenetic and fluorescence in situ hybridization a nalysis showed a de novo 46,XY,del(13) (q33.2-->qter) with no visible trans location, By using microsatellite markers, the deletion breakpoint was mapp ed to a 350-kb region between D13S274 and D13S1311 and was paternal in orig in. An analysis of 13q deletions with NTDs, including the present case, sug gests that a deletion in 13q33-34 is sufficient to cause an NTD, The deleti ons associated with NTDs are distal to and nonoverlapping with the previous ly defined critical region in 13q32 for the major malformation syndrome [Br own et al,, 1999: Am J Hum Genet 57: 859-866], Our analysis also suggests t hat one or more genes in 13q33-34 produces NTDs by haploinsufficiency. (C) 2000 Wiley-Liss, Inc.