A case of childhood acute myeloid leukemia AML (M5) with a neocentric chromosome neo(1)(qter→q2324::q2324→q43→neo→q43→qter) and tetrasomy of chromosomes 8 and 21

Hyperdiploidy is rarely observed in childhood acute myeloid leukemia (AML). Described here is the case of a 2½-year-old girl with AML-M5 and 51 chromosomes characterized by double tetrasomy of chromosomes 8 and 21 and also a neocentric derivative chromosome neo(1)(qter→q2324::q2324→q43→neo→q43→qter). Little is known about the prognostic significance of these chromosomal abnormalities in childhood AML. In the actual case, complete remission was achieved after chemotherapy, which continued for 7 months. No acquired neocentric chromosome 1 has been described previously, even though neocentromere formation has been reported for other chromosomes in neoplasms.     

Tetrasomy 9p caused by idic (9) (pter→q13→pter)

Cytogenetic investigation on a malformed male infant showed an extra chromosome similar to chromosome 9 in all metaphases studied. GTG, CBG, and G-11 staining suggested that the extra chromosome was an abnormal 9, permitting the identification of the chromosome constitution as 47,XY, +idic (9) (pter→q13→pter).     

Two novel β-thalassemia alleles: Poly A signal (AATAAA→AAAA) and −92 C→T

β-Thalassemia (β-thal) is a hereditary anemia caused by mutations in the β-globin gene encoding the β-globin chain of hemoglobin A. In its homozygous form, the disease is characterized by a hemolytic hypochromic anemia, hepatosplenomegaly, skeletal deformation, mongoloid facies, and cardiac enlargement. The heterozygous form is usually asymptomatic but is sometimes associated with moderate anemia and splenomegaly. More than 100 β-thal mutations have been detected in the β-globin gene (Kazazian, 1990). Here we report two new β-thal mutations and observation of another rare allele, which was found previously in a single individual. © 1995 Wiley-Liss, Inc.     

Atypical phenotype associated with deletion (15) (pter → q11::q13 → qter)

We report on a 10-year-old boy with an interstitial deletion within the region of bands 15q11 → q13. Authors have associated the manifestation of the Prader-Willi syndrome (PWS) with variable deletions involving the bands q11 → q13. Our patient had atypical manifestations not usually associated with PWS, ie, normal stature, proportionally sized hands and feet, normal genitalia, and was nonambulatory and severely mentally retarded. This case emphasized the clinical diversity seen in proximal 15q deletions in the region considered to be correlated with the PWS.     

Interstitial deletion 2q31→q33

We present an 8-month-old female with severe retardation of growth and development, multiple congenital anomalies, and an interstitial deletion del(2)(q31→q33) including results of cytogenetic and gene marker studies. The manifestations of this infant are compared with those of four other known patients with a partial del(2q).     

Monosomy 9p24→pter and trisomy 5q31→qter: Case report and review of two cases

Partial deletion of the short arm of chromosome 9 (p24→pter) and partial duplication of the long arm of chromosome 5 (q32→qter) were observed in an abnormal boy who died at age 8 weeks of a complex cyanotic cardiac defect. He also had minor anomalies, sagittal craniosynostosis, triphalangeal thumbs, hypospadias, and a bifid scrotum. Two other infants with similar cytogenetic abnormalities were described previously. These patients had severe congenital heart defect, genitourinary anomalies, broad nasal bridge, low hairline, apparently low-set ears, short neck, and triphalangeal thumbs, in common with our patient. We suggest that combined monosomy 9p23,24→pter and trisomy 5q31,32→qter may constitute a clinically recognizable syndrome. © 1995 Wiley-Liss, Inc.     

Malformation syndrome of duplication 12q24.1→qter

While duplication and deletion of the short arm of chromosome 12 cause well-recognized syndromes, duplication of the long arm of chromosome 12 is rarely observed. We are reporting a duplication of chromosome 12 distal to band q24.1 in a five-month-old child. His chromosome constitution is 46,XY,-4, + der(4),t(4:12)(p16;q24.1)mat. The balanced translocation is also carried by his maternal grandmother and two of the mother's brothers. The malformation syndrome consisted of unusual facial appearance and anomalies of the musculoskeletal, cardiovascular, genitourinary, and central nervous systems. Four previously reported patients had similar break points on chromosome 12 with similar malformations; therefore, phenotype-karyotype correlation suggests a definitive malformation syndrome associated with duplication of chromosome region 12q24.1→qter.     

Duplication 11p11.3 → 14.1 to meiotic crossing-over

An infant with macular dysfunction, cleft lip and palate, and developmental delay was shown to have an inverted duplication of 11p11.3→p14.1 on the basis of meiotic recombination subsequent to an intrachromosomal “shift” in his mother. A half-sister had previously been shown [3] to have the reciprocal recombinant with resultant deletion of 11p11.3→11p14.1.     

Adjacent-2 disjunction of a maternal t(9;22) leading to duplication 9pter→q22 and deficiency of 22pter→q11.2

The proposita presented at birth with multiple congenital anomalies including craniofacial anomalies, bilateral cleft lip and palate, abnormalities of the urogenital system, talipes equinovarus, and the DiGeorge sequence. Cytogenetic investigation showed a 46,XX,- 22,+der(9)t(9;22)(q22;q11.2) karyotype. The mother, maternal uncle, and maternal grandmother of the infant are carriers of a reciprocal balanced translocation involving chromosomes 9 and 22 at regions q22 and q11.2, respectively. The unbalanced karyotype seen in the proposita arose due to an adjacent-2 disjunction of the quadrivalent in the mother. Prenatal diagnosis of the second pregnancy of this woman showed a similar karyotype. Review of the literature shows that adjacent-2 disjunction may occur preferentially when certain chromosomes are involved in translocations.     

Familial ligand-defective apolipoprotein B-100: Simultaneous detection of the ARG3500→GLN and ARG3531→CYS mutations in a French population

Familial ligand-defective apolipoprotein B-100 (FDB) is an autosomal dominant disorder leading to plasma LDL cholesterol elevation and coronary artery disease (CAD). Two specific mutations in the APOB gene—R3500Q and R3531C—induce FDB. We report an original method to detect both mutations simultaneously, based upon PCR-mediated, site-directed mutagenesis and double restriction of a unique PCR product. With this method we have investigated the prevalence of these mutations in 1,040 French patients. The R3500Q mutation was found in five probands. Genotypes were determined for 10 APOB polymorphic markers and were consistent with the common European ancestral haplotype previously reported. The only exception was one FDB proband who did not harbor the 48 repeat allele of the 3′HVR. Additionally, the first two R3531C mutations were identified in French probands. Genotypes were consistent with a previously reported haplotype, suggesting that this is another mutation of European ancestry. Hum Mutat 10:160–163, 1997. © 1997 Wiley-Liss, Inc.     

Duplication 9q34→qter identified by chromosome painting

We have studied an infant with multiple anomalies and a 46,XY,12p+ karyotype. Parental chromosomes were normal, and it was not possible to determine the identity of the extra material on chromosome 12 cytogenetically. Chromosome painting with probes from a chromosome 9 library identified this material as coming from chromosome 9, and cytogenetics established the duplication as 9q34→qter. Comparison of this patient with others reported with partial dup(9q) documented excellent concordance of minor anomalies, most notably dolichocephaly, “;deep-set”; eyes, short horizontal palpebral fissures, beaked nose, micrognathia, arachnodactyly, and developmental delay. Identification of cytogenetically indeterminate abnormalities by molecular cytogenetics is very important, as it permits prognosis to be offered for families of newborn infants with unbalanced karyo-types. © 1993 Wiley-Liss, Inc.     

Trisomy 1q42→qter in a sister and brother: Further delineation of the “trisomy 1q42→qter Syndrome”

We report on a 22-year-old woman and her 21-year-old brother with mild mental retardation, long face, prominent forehead, retrognathia, and (relative) macrocephaly. At birth they were small for date, their length is now below the 10th centile. Chromosome analysis demonstrated a nearly pure trisomy 1q42→qter in both patients due to unbalanced segregation of a paternal reciprocal balanced translocation 46,XY,t(1;15) (q42;p11). This is the second report of a nearly pure trisomy 1q42→qter. When comparing the manifestations of our patients with those of other reported cases we conclude that the most characteristic clinical manifestations of this syndrome are macrocephaly, prominent forehead, micro/retrognathia, large fontanelle, intrauterine growth retardation, postnatal growth retardation, and mental retardation. © 1995 Wiley-Liss, Inc.     

Replication banding and molecular studies of a mosaic,unbalanced dic(X;15)(xpter→xq26.1::15p11→15qter)

We present a patient with a chromosomal mosaicism involving the X chromosome. One cell line is 45,X and the other has a de novo paternally derived dicentric X;15 translocation. Her karyotype is therefore 45,X/45,X,dic(X;15)(Xpter→Xq26.1: : 15p11→15 qter) based on G-banding. The presence of 2 centromeres on the derivative X was confirmed by fluorescence in situ hybridization (FISH) and a deletion of Xq26.1→qter was confirmed by polymerase chain reaction (PCR) using DXS52 and DXYS154. Replication banding studies indicate that the derivative X is late replicating. Based on these studies, it is unclear whether inactivation has spread to proximal 15q. The patient has a unique phenotype distinct from Ullrich-Turner or Prader-Willi syndromes, but includes ataxia and language delay which are commonly seen in Angelman syndrome. These findings are contrary to those anticipated since deficiency of paternal genes at 15q12 typically leads to Prader-Willi syndrome. Molecular analysis of PCR-based polymorphisms of chromosome 15 and X indicates that uniparental disomy is not present for the X chromosome or chromosome 15 in either cell line. It is hypothesized that her phenotype results from the interaction of the 2 abnormal genotypes. Each abnormality may be diluted by the mosaicism and, in the derivative X line, by the possible variation among cells of inactivation spreading to chromosome 15. © 1995 Wiley-Liss, Inc.     

Girl with combined cellular immunodeficiency,pancytopenia, malformations,deletion 11q23.3 → qter,and trisomy 8q24.3 → qter

We describe here a 3‐year‐old girl demonstrating combined cellular immunodeficiency of B‐ and T‐cells, pancytopenia, multiple anomalies, and severe mental retardation. Cytogenetic analysis and fluorescent in situ hybridization (FISH) indicated an unbalanced translocation of chromosomes 8q and 11q, resulting in monosomy 11q23.3‐qter and trisomy 8q24.3‐qter. The association of cellular immunodeficiency and partial deletion 11q and/or partial trisomy 8q has not been described previously; however, the 11q deletion has been reported with humoral immunodeficiency or pancytopenia. Some one‐third to one‐half of patients with partial monosomy 11q were reported to have pancytopenia, which has been related to the absence of the 11q23‐q24 region. Our case narrows down the critical interval for thrombo‐ or pancytopenia to 11q23.3‐q24 and excludes both the ATM (which resides on 11q23.1) and the MLL genes as possible candidate genes. We are proposing that haploinsufficiency of the NFRKB gene on 11q24‐q25 and/or the ETS‐1 proto‐oncogene on 11q24 may have caused or contributed to the immunodeficiency (decreased levels of B‐ and T‐lymphocytes) in our patient. © 2002 Wiley‐Liss, Inc.     

Diagnosis of chromosome 3 duplication q23→qter,deletion p25→pter in a patient with the C (trigonocephaly) syndrome

The cells of a deceased patient previously reported to have the C (trigonocephaly) syndrome were reinvestigated because his phenotype resembled that of a patient with a duplication-deficiency of chromosome 3. This diagnosis was confirmed using fibroblasts grown from frozen cells, and his mother was shown to carry an inversion of chromosome 3 in her peripheral blood leukocytes. His findings are compared to those of another patient with the C trigonocephaly syndrome with normal chromosomes and to others from the literature. At least one other patient from the literature has a phenotype compatible with “3q duplication syndrome”.     

Interstitial Duplication of 7(q22→q34)

We report on a 3-year-old boy with an interstitial duplication of 7(q22→q34), confirmed with fluorescent in-situ hybridization. He had post-natal growth retardation, developmental delay, frontal and parietal bossing, deep-set eyes, strabismus, bilateral optic nerve hypoplasia, and mild dilatation of the cerebral ventricles. His Phenotype was not significantly different from that of the three previously reported patients with interstitial duplication of the smaller segment 7(q22→q31). © 1993 Wiley-Liss, Inc.     

Inverted duplication of 22pter → q11.21 in cat-eye syndrome

A young man was diagnosed as having Zimmerman-Laband syndrome (ZLS) on the basis of gingival fibromatosis and absence of nails on thumbs and halluces in addition to other anomalies. He also had profound mental retardation.