Normal expression of the Fanconi anemia proteins FAA and FAC and sensitivity to mitomycin C in two patients with Seckel syndrome

Seckel syndrome is a rare autosomal recessive disorder. The classical prese ntation includes pre- and postnatal growth deficiency, mental retardation, and characteristic facial appearance. There have been several reports of as sociated hematological abnormalities and chromosomal breakage, findings sug gestive of Fanconi anemia (FA), We tested for these findings in two Arabic patients with this syndrome, We compared the growth profile of lymphoblasto id cells from our patients and their parents with the FA group A cell line HSC72 in the presence and absence of mitomycin C (MMC). By Western analysis , we also determined the expression of FAA and FAG, two FA disease gene pro ducts that together account for approximately 80% of FA. Unlike HSC72 cells , cells from the patients were resistant to MMC, and both FAA and FAC prote ins were expressed at similar levels in all cell lines, There is an increas ing recognition of clinical variability and perhaps genetic heterogeneity i n Seckel syndrome, Our results demonstrate that cross-link sensitivity comp arable to FA is not a uniform finding in patients with Seckel syndrome. Am. J. Med. Genet, 83:388-391, 1999, (C) 1999 Wiley-Liss, Inc.