Molecular analysis in newborns from Texas affected with galactosemia

The spectrum of mutations in the Galactose‐1‐phosphate uridyl transferase (GALT) gene is described in 11 cases of classic galactosemia and 38 of Duarte‐2 type identified by the Texas Newborn Screening Program. Blinded studies were done by automated DNA sequencing of all the 11 exons and the exon‐intron boundaries of the GALT gene using genomic DNA isolated from dry blood spots. Fourteen different mutations (11 missense mutations, 2 nonsense mutations and 1 splicing mutation) were detected in 94 of the 98 mutant alleles (diagnostic efficiency of 96%). The prevalent mutations were N314D (41%), Q188R (37%) and K285N (4%). The other less frequent mutations were IVS2‐2A>G and S135L (3% each), T138M (2%) and T23A, H184Q, Y251S, L195P, Q207X, L264X, Q344K, and A345D (1% each). Three novel mutations, T23A, Q207X, and A345D, were identified. Our study supports previous findings that N314D and Q188R are prevalent in Hispanics and Whites and K285N was only observed in Whites. The IVS2‐2A‐>G mutation is probably ethnic specific because it was identified exclusively in Hispanics. S135L, a prevalent mutation in Blacks, was also present in 3 Hispanics. Two unusual genotypes were observed in 2 patients homozygous for the Duarte‐2 N314D allele and heterozygous for a novel mutation (Q207X‐ N314D/N314D in a classic galactosemia and T23A‐ N314D/N314D in a Duarte‐2 case). The detection of GALT gene mutations in newborns from Texas should focus first on N314D, Q188R, K285N, IVS2‐2A>G, S135L and T138M. Other exons and exon‐intron boundaries would have to be studied if either one or no mutations are found in the primary screening. © 2001 Wiley‐Liss, Inc.