Yoshiharu Wakita

Probable assignment of soluble isocitrate dehydrogenase (IDH1) to 2q33.3

SummaryGene 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.

Assignment of ABO locus to 9q31.3----qter by study of a family in which an intrachromosomal shift involving chromosome 9 is segregating

SummaryA family in which an intrachromosomal shift, dir ins(9) (q22.1q31.3;q34.3), was segregating is described. A meiotic crossing over in the noninsertional loop of the carrier mother appeared to have resulted in the proband with a recombinant chromosome 9 duplicating the interstitial segment 9q22.1→q31.3. The study of ABO and AK1 phenotypes in the family showed that the proband was also a recombinant for the ABO locus. These results allowed us to assign the ABO locus to 9q31.3→qter on the cytogenetic basis.

Duplication of 2p25: confirmation of the assignment of soluble acid phosphatase (ACP1) locus to 2p25

SummaryThe 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.

The critical monosomic segment involved in 4p- syndrome: A high-resolution banding study on five inherited cases

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) (p15.2;p11.21)mat (two cases, related). The results suggested that monosomy for the proximal half of the 4p16 band is sufficient to express 4p-syndrome.

Interstitial deletion of the long arm of chromosome 2: A case report and review of the literature

SummaryA girl with mental retardation and multiple anomalies was shown to have a de novo interstitial deletion of the long arm of chromosome 2(2q23.3→q24.2) by the use of high resolution banding technique. Review of the literature revealed that her clinical features resembled those of the previously reported cases with monosomy for the middle portion of 2q.

De novo complex chromosome rearrangement in identical twins with multiple congenital anomalies

SummaryA de novo and apparently balanced complex chromosome rearrangement (CCR) was found in monozygotic (MZ) twin infants with multiple congenital anomalies. The rearrangement involved 4 chromosomes with 6 breakpoints including 2p23, 2q13, 2q21.1, 3p23, 11q13.1, and 12q24.1. This seems to be the first report of a CCR in MZ twins. The relationship between this chromosome abnormality and MZ twinning is discussed.

Pallister-Killian syndrome: Cytogenetic and biochemical studies

SummaryPallister-Killian syndrome is characterized by specific dysmorphic features and tissue-limited mosaicism for tetrasomy 12p. We describe an additional case of a stillborn neonate, who had not only the specific craniofacial features seen in the syndrome but also various internal malformations. Cytogenetic study showed that an extra F-like chromosome was found in 43% of lymphocytes and in 90% of fibroblasts. The high resolution G-banded pattern of the extra chromosome was consistent with an interpretation of an i(12p). The diagnosis of tetrasomy 12p was further confirmed by four-fold gene dosage effects in fibroblasts for GAPD and LDH-B, whose locus was both assigned to the 12p. The proportion of tetrasomic cells in fibroblasts decreased remarkably during long-term cultures. These results suggest that the tissue specific mosaicism in the syndrome is not simply a result of preferential selection against lymphocytes carrying the marker but may be related to the time of mosaic formation as well as the somatic selection of different intensity in different tissues.

Reproductive risk of paracentric inversion carriers: Report of two unrelated cases with paracentric inversion of the long ARM of chromosome 3

SummaryTwo unrelated cases with a paracentric inversion involving the long arm of a chromosome 3 were described. One case was a 29-year-old female with habitual spontaneous abortions. The karyotype was 46,XX,inv(3)(q25q27). The other case was a two year one month-old girl with growth and psychomotor retardation and multiple minor anomalies. She was found to have a recombinant chromosome 3 resulting from a paternal paracentric inversion. The karyotype of the patient was 46,XX, rec(3),dup(q26.3),inv(3)(q12q29)pat. The review of previously reported cases showed a considerable risk for live-born recombinants derived from parental paracentric inversions and the analysis of reproductive histories of inversion carriers suggested a possible contribution of this type of chromosome abnormalities to the cause of spontaneous abortions.

Distal 14q trisomy syndrome in two siblings: Further delineation of its phenotype

SummaryWe describe two siblings with distal 14q trisomy resulting from a maternal translocation t(5;14)(p15.33;q31.2): a male newborn infant who died at the age of 1 month and a prenatally diagnosed male fetus. They showed almost identical phenotypic abnormalities. Review of the literature suggests the occurrence of a distal 14q trisomy syndrome, which is clinically characterized by mental retardation, growth failure, frontal bossing, facial asymmetry, hypertelorism, sparse eyebrows and eyelashes, short prominent nose, cupid bow upperlip, micrognathia, and low-set and posteriorly rotated ears. It seems likely that triplication of the segment 14q32.1→qter is critical for clinical manifestation of this syndrome.