Duplication of segment 1p21 following paternal insertional translocation, ins(6;1)(q25;p13.3p22.1)

A moderately mentally retarded 3 year old boy showed minor anomalies including a prominent forehead and flat occiput, exophthalmos, large and prominent ears, high arched palate, umbilical hernia, sacral dimple, and irregular position of the toes. Cardiac sonography disclosed a chorda running through the left ventricle. Cytogenetic investigation of the family showed a balanced insertional translocation of segment 1p13→p22 into distal 6q in the father which had led, through unbalanced segregation, to duplication of 1p13.3→p22.1 in the proband. Familial duplication of such a small interstitial segment of 1p has not been reported previously, and the paucity of abnormal physical findings in the proband compared to previous patients with a similar aberration is remarkable.


Keywords: chromosome duplication 1p; dual colour FISH; unbalanced insertional translocation     

Familial reciprocal translocation, t(2;10)(p24;q26), resulting in duplication 2p and deletion 10q

We describe a familial reciprocal translocation between the distal part of the short arm of chromosome 2 and the long arm of chromosome 10. Five individuals in two generations had multiple congenital anomalies. Their karyotypes were 46, XX or XY,−10, + der(10), t(2;10)(p24;q26). Seven persons were balanced translocation carriers whose karyotypes were 46, XX or XY, t(2;10)(p24;q26). Common manifestations included mental retardation, strabismus, narrow high-arched palate, wide alveolar ridges, other facial abnormalities, genital abnormalities and mutism. The phenotype of the unbalanced individuals is compared to that of previously published cases of the syndrome of partial duplication 2p and to reported patients with partial deletion of 10q.     

Adrenal myelolipoma with translocation (3;21)(q25;p11)

Adrenal myelolipoma (ML) is a rare, benign, nonfunctioning tumor-like lesion composed of mature adipose tissue interspersed with bone marrow-like hematopoietic elements in various proportions. It occurs usually in adults and is frequently asymptomatic in about half of cases. The histogenesis of adrenal ML is not clear and this lesion has been found to be associated with endocrine disorders, other adrenal dysfunction and tumors, and hyperstimulation with adrenocorticotropic hormone. Specific chromosomal abnormalities, however, have not been observed in such cases. Herein, we report a typical case of adrenal ML found incidentally in a 26-year-old man. Conventional cytogenetic techniques demonstrated balanced translocation between bands 3q25 and 21p11 in 9 of 20 metaphases analyzed in cultured tumor cells. To the best of our knowledge, this is the first reported case of adrenal ML showing chromosomal abnormality. This finding would indicate that adrenal ML is a bona fide neoplasm and the possibility of derivation from misplaced hematopoietic cells may be alternatively taken into consideration in view of the similar genetic changes in hematopolietic neoplasms.     

Interstitial del(20)(q11.2q12) - clinical and molecular cytogenetic characterization

A 2-year-old male patient with dysmorphic facial features and multiple congenital anomalies suggestive of a chromosome syndrome is presented. The facial features consisted of a large and high forehead, mild metopic ridging, a small triangular face, depressed nasal bridge, microphthalmia (right more than the left), protruding ears, and mildly prominent anteverted nose with long and smooth philtrum. Cytogenetic analysis showed 46,XY,del(20)(q11.2q12). Parental karyotypes were normal. Molecular characterization of del(20)(q11.2q12) by high-resolution microarray comparative genomic hybridization (arrayCGH) showed an approximately 6.8 Mb deletion. To our knowledge this is the first report of a de novo interstitial del(20)(q11.2q12) characterized by arrayCGH.     

Interstitial deletion of chromosome 5 in a neonate due to maternal insertion,ins(8;5)(p23;q33q35)

We describe an infant girl with an interstitial deletion of chromosome bands 5q33 to 5q35 inherited from a maternal interchromosomal insertion ins(8;5)(p23;q33q35) which was demonstrated by fluorescent in situ hybridization with whole chromosome paints. Physical anomalies included hypertonicity, microcephaly, short neck, apparently low-set ears, micrognathia, camptodactyly, mild rocker bottom feet, and hammer toe. Cardiac anomalies included a large ventricular septal defect, patent ductus arteriosus, pulmonary hypertension and hypoplastic right ventricle. She died at age 3 months. Am. J. Med. Genet. 86:289–293, 1999. © 1999 Wiley-Liss, Inc.     

Interstitial deletion of chromosome 5 in a neonate due to maternal insertion, ins(8;5)(p23;q33q35).

We describe an infant girl with an interstitial deletion of chromosome bands 5q33 to 5q35 inherited from a maternal interchromosomal insertion ins(8;5)(p23;q33q35) which was demonstrated by fluorescent in situ hybridization with whole chromosome paints. Physical anomalies included hypertonicity, microcephaly, short neck, apparently low-set ears, micrognathia, camptodactyly, mild rocker bottom feet, and hammer toe. Cardiac anomalies included a large ventricular septal defect, patent ductus arteriosus, pulmonary hypertension and hypoplastic right ventricle. She died at age 3 months.     

Molecular and clinical characterization of a recurrent cryptic unbalanced t(4q;18q) resulting in an 18q deletion and 4q duplication

Recurrent constitutional non-Robertsonian translocations are very rare. We present the third instance of cryptic, unbalanced translocation between 4q and 18q. This individual had an apparently normal karyotype; however, after subtelomere fluorescence in situ hybridization (FISH), he was found to have a cryptic unbalanced translocation between 4q and 18q [ish der(18)t(4;18)(q35;q23)(4qtel+,18qtel-)]. Oligonucleotide array comparative genomic hybridization (aCGH) refined the breakpoints in this child and in the previously reported child and indicated that the breakpoints were within 20 kb of each other, suggesting that this translocation is, indeed, recurrent. A comparison of the clinical presentation of these individuals identified features that are characteristic of both 18q- and 4q+ as well as features that are not associated with either condition, such as a prominent metopic ridge, bitemporal narrowing, prominent, and thick eyebrows. Individuals with features suggestive of this 4q;18q translocation but a normal karyotype warrant aCGH or subtelomere studies.     

Familial,balanced insertional translocation of chromosome 7 leading to offspring with deletion and duplication of the inserted segment, 7p15 → 7p21

We report an uncle and niece with duplication and deletion, respectively, of segment 7p15 → 7p21 originating from a balanced, intrachromosomal insertion in their mothers. The proposita had prenatal and postnatal growth deficiency, retarded psychomotor development, microcephaly, wide cranial sutures, ocular hypertelorism, small palpebral fissures, apparently low-set and malformed ears, cleft palate, congenital heart defect, hypoplasia of the distal phalanx of first fingers, rocker-bottom feet, persistent cloaca, and imperforate anus. She died at three months. Her maternal uncle has duplication of this segment and is alive at 32 years. He has severe mental deficiency, but normal growth; communicating hydrocephalus was diagnosed at three months.     

Familial partial trisomy 6q syndromes resulting from inherited ins (5;6) (q33;q15q27)

Two cases are reported of familial partial trisomy 6q syndrome due to segregation of ins(5;6) (q33;q15q27) in three generations. The common clinical features include growth and mental retardation, feeding difficulty during infancy, microcephaly with downward slanting palpebral fissures, flattened nasal bridge with anteverted and flared nares, long philtrum, high arched palate, partially opened and protruding mouth with receding chin, deep transverse creases of the ears, three creases on the 4th fingers, clinodactyly of the 5th fingers with a single crease, and other dermatoglyphic findings. These characteristic features of two patients appear to make partial trisomy 6q a clinically recognizable syndrome.     

Subtelomeric familial translocation t(2;7)(q37;q35) leading to partial trisomy 7q35→qter: Molecular cytogenetic analysis and clinical phenotype in two generations

Few patients with trisomy of the most distal region of chromosome 7q have been described. We report on a familial translocation t(2;7)(q37;q35) leading to trisomy 7q35→7qter in a child and her paternal uncle and a minimal deletion of distal 2q as demonstrated by FISH with probes located in the chromosome 2q subtelomeric region. The clinical phenotype included macrocephaly and low‐set ears, also found in other reported patients trisomic for the distal part of chromosome 7q. Phenotypic findings probably useful for the clinical diagnosis include normal size at birth, large head with frontal bossing, low‐set ears of normal shape, small nose and low nasal bridge, feeding difficulties in infancy, and severe neurodevelopmental delay. Am. J. Med. Genet. 93:349–354, 2000. © 2000 Wiley‐Liss, Inc.     

Peripheral T-cell lymphoma with t(6;14)(p25;q11.2) translocation presenting with massive splenomegaly

Recurrent chromosomal translocations associated to peripheral T-cell lymphomas (PTCL) are rare. Here, we report a case of PTCL, not otherwise specified (NOS) with the karyotype 46,Y,add(X)(p22),t(6;14)(p25;q11) and FISH-proved breakpoints in the IRF4 and TCRAD loci, leading to juxtaposition of both genes. A 64-year-old male patient presented with mild cytopenias and massive splenomegaly. Splenectomy showed diffuse red pulp involvement by a pleomorphic medium- to large-cell T-cell lymphoma with a CD2+ CD3+ CD5? CD7? CD4+ CD8+/? CD30? TCRbeta-F1+ immunophenotype, an activated cytotoxic profile, and strong MUM1 expression. The clinical course was marked by disease progression in the bone marrow under treatment and death at 4 months. In contrast with two t(6;14)(p25;q11.2)-positive lymphomas previously reported to be cytotoxic PTCL, NOS with bone marrow and skin involvement, this case was manifested by massive splenomegaly, expanding the clinical spectrum of PTCLs harboring t(6;14)(p25;q11.2) and supporting consideration of this translocation as a marker of biological aggressiveness.     

Derivative (7)t(7;8)(q34;q21). a new additional cytogenetic abnormality in acute promyelocytic leukemia

Cytogenetic abnormalities in acute myelocytic leukemia (AML) have been identified as one of the most important prognostic factors. The t(15;17) is associated with high rates of complete remission and event-free survival. Secondary chromosomal changes are also present in approximately one third of patients with newly diagnosed acute promyelocytic leukemia (APL). Indeed, the gain of whole chromosome 8 may be involved in the course of APL under C-MYC gene dosage effect theory. Complete or partial loss of the long arm of chromosome 7 region has been recognized in preleukemic myelodysplasia or unfavorable AML. We report here two original APL cases in which a new additional chromosomal abnormality, der(7)t(7;8)(q34;q21), is associated with the t(15;17)(q22;q21). This recurrent abnormality results in a partial loss of 7q associated with a partial 8q trisomy. As the 7q and 8q breakpoints were similar in both cases, the involvement of these critical regions in the pathogenesis and outcome of APL disease has to be determined.     

Molecular cytogenetic characterization of a recombinant chromosome rec(22)dup(22q)inv(22)(p13q12.2)

In 1985, Frydman et al. [1985: Clin Genet 27:414-419] described a syndrome characterized by growth failure, microcephaly, persistent hyperplastic primary vitreous (PHPV) with microphthalmia, cleft palate, connective tissue abnormality, mental retardation, and spastic quadriplegia. The syndrome was termed as oculo-palato-cerebral dwarfism. The first patients described were offsprings of a consanguineous couple of Moroccan Jewish descent, suggesting autosomal recessive inheritance. An additional case was reported by Pellegrino et al. [2001: Am J Med Genet 99:200-203] in 2001. The clinical features were milder than the original cases, and there was no consanguinity. We report a third patient with oculo-palato-cerebral syndrome, supporting autosomal recessive inheritance, and a detailed comparison with the previous cases. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html.