Gene dosage effects for soluble isocitrate dehydrogenase (IDH1) were investigated in four unrelated cases with abnormalities involving the long arm of chromosome 2. Case 1 was trisomic for 2q33.3----qter, Case 2 monosomic for 2q33.3----q35, Case 3 trisomic for 2q11.2----q24.2, and Case 4 monosomic for 2q23----q24.2. These abnormalities were de novo except in Case 1, where trisomy 2q resulted from a maternal translocation. The red cell IDH1 levels were significantly reduced in Cases 1 (41.4% of normal value) and 2 (51.9%), while they were normal in Cases 3 and 4. The low IDH1 level also in the father of Case 1 (43.6%), together with the common electrophoretic phenotype of IDH1 in red cells as well as leukocytes, led us to suppose that Case 1 was really heterozygous for common and probable null alleles, and that the IDH1 gene locus could be excluded from 2q33.3----qter. On the other hand, normal IDH1 values in the parents of Case 2 were consistent with the hemizygosity for this locus in Case 2. The results suggested that the IDH1 locus could be assigned to the 2q33.3 band, especially the proximal portion of it.
SummaryIn an attempt to determine the critical monosomic segment involved in 4p-syndrome, we studied the precise breakpoints of five inherited cases with the syndrome using a high-resolution banding technique. The 5 patients ranged in age at diagnosis from newborn to 15 months, 4 of whom could be clinically diagnosed as having 4p-syndrome. Common clinical features included mental retardation, low birth weight, growth failure, hypotonia, microcephaly, peculiar facial dysmorphia and ear malformations. Karyotypes of the 5 were 46,XX,-4, +der(4),t(4;21) (p16.1 ;q22.3)pat; 46,XX,-4,+der(4), inv ins(4;9)(p15.32p16.3;q34.3)pat; 46,XX, rec(4),del p,inv(4)(p15.2q35)pat; and 46,XX,-4, + der(4),t(4;18) (pl5.2;pll.21)mat (two cases, related). The results suggested that monosomy for the proximal half of the 4p16 band is sufficient to express 4p-syndrome.
The regional localization of the gene coding for soluble acid phosphatase (ACP1) has been under debate in the two different chromosome regions, 2p23 or 2p25. Gene dosage studies in a case with a karyotype of 46,XX,dir dup(2) (p25.1----p25.3) showed that the ACP1 activity was increased to 1.4 times the mean value of normal individuals with the same ACP1 phenotype, while the level of soluble malate dehydrogenase (MDH1) was normal. These gene dosage effects indicated that the ACP1 gene locus can be mapped to 2p25.
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