Partial monosomy 9p (9p22.2-->pter) and partial trisomy 18q (18q21.32-->qter) in a female infant with anorectal malformations

We report a female infant with a karyotype of 46,XX,der(9)t(9;18)(p22.2;q21.32)pat and the phenotypic features of craniofacial dysmorphisms, developmental delay, hypotonia, horizontal nystagmus, strabismus, congenital heart defects, clubfoot, and anorectal malformations with an anterior ectopic anus and a stenosed anal opening. Array comparative genomic hybridization revealed a 16.93-Mb deletion at 9p24.3-p22.2 encompassing the FREM1 gene and a 20.43-Mb duplication at 18q21.32-q23 encompassing the PIGN gene. We speculate that dual genome imbalances in FREMI at 9p22.3 and in PIGN at 18q21.3 are most likely responsible for the abnormal development of anorectum in this patient.     

Trisomy 9p due to paternal translocation, t(9;13) (q13;q12).

A 16-year-old girl with trisomy 9p is described. She had a short stature, severe mental retardation and the following abnormal clinical findings: peculiar face with hypertelorism, downward slanting palpebral fissures, convergent strabismus, a bulbous nose with broad and prominent bridge, short upper lip, narrow, high-arched palate; short neck with low hairline; severe kyphoscoliosis and a congenital clubfoot deformity; hypoplasia and dysplasia of several phalanges of the fingers and toes and some nails, a delay by about 6 years in bone age, and remarkable dermatoglyphic patterns. The father and 3 other family members carried a balanced translocation between chromosomes 9 and 13, t(9;13)(q13;q12).     

An infant with trisomy 9pter yields 9q22 resulting from 3:1 segregation in a 46,XX t(1;9) (p36;q22) mother.

A newborn infant with a 47,XY,+ der(.),t(1;9) (p36;q22)mat chromosome complement and the clinical features of the 9p trisomy is described. A review of the reproductive histories of five cases with trisomy 9pter yields 9q21 or 22 indicate that the balanced translocation mothers of these infants may have as high as a 23% chance of producing a chromosomally unbalanced offspring due to 3:1 disjunction.     

Spectral karyotyping and fluorescence in situ hybridization analysis of de novo partial trisomy 7p (7p21.2-->pter) and partial monosomy 12q (12q24.33-->qter)

An 8-year-old boy presenting with hypotonia, moderate mental retardation, developmental delay, and psychomotor retardation is reported. Magnetic resonance imaging of the brain at age 3 years revealed a Dandy-Walker variant. Cytogenetic analysis of the peripheral blood revealed a derivative chromosome 12 with unknown additional material attached to the distal region of the long arm of chromosome 12. The parental karyotypes were normal. Spectral karyotyping (SKY) using the 24-color SKY probes and fluorescence in situ hybridization (FISH) using the specific 7p, 7q, 12p, and 12q telomeric probes confirmed a duplication of distal 7p and a deletion of terminal 12q. The karyotype of the proband was designated as 46,XY.ish der(12)t(7;12) (p21.2;q24. 33)(SKY+, 7pTEL+, 12qTEL-). The present case provides evidence for the association of partial trisomy 7p (7p21.2-->pter) and partial monosomy 12q (12q24.33-->qter) with a cerebellar malformation and the usefulness of SKY and FISH in the identification of a de novo aberrant chromosome resulting from an unbalanced translocation.     

Partial trisomy 10p and familial translocation t(7;10)(p22;p12)

Summary A girl with partial trisomy for the short arm of chromosome 10(p12pter) due to mal chromosome segregation in the father 46,XY,t(7;10)(p22;p12) is described. The major abnormalities in this case are: mottled skin, mid-facial hypoplasia, low percentiles for weight, length, and head circumference, and club feet.To whom offprint requests should be sent     

Complex rearrangement involving 9p deletion and duplication in a syndromic patient: genotype/phenotype correlation and review of the literature

We describe a 7-year-old boy with a complex rearrangement involving the whole short arm of chromosome 9 defined by means of molecular cytogenetic techniques. The rearrangement is characterized by a 18.3 Mb terminal deletion associated with the inverted duplication of the adjacent 21,5 Mb region. The patient shows developmental delay, psychomotor retardation, hypotonia. Other typical features of 9p deletion (genital disorders, midface hypoplasia, long philtrum) and of the 9p duplication (brachycephaly, down slanting palpebral fissures and bulbous nasal tip) are present. Interestingly, he does not show trigonocephaly that is the most prominent dysmorphism associated with the deletion of the short arm of chromosome 9. Patient's phenotype and the underlying flanking opposite 9p imbalances are compared with that of reported patients and the proposed critical regions for 9p deletion and 9p duplication syndromes.     

Synthesis of alpha-Manp-(1-->2)-alpha-Manp-(1-->3)-alpha-Manp-(1-->3)-Manp, the tetrasaccharide repeating unit of Escherichia coli O9a, and alpha-Manp-(1-->2)-alpha-Manp-(1-->2)-alpha-Manp-(1-->3)-alpha-Manp-(1-->3)-Manp, the pentasaccharide repeating unit of E. coli O9 and Klebsiella O3

The tetrasaccharide repeating unit of Escherichia coli O9a, alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->3)-D-Manp, and the pentasaccharide repeating unit of E. coli O9 and Klebsiella O3, alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->3)-D-Manp, were synthesized as their methyl glycosides. Thus, selective 3-O-allylation of p-methoxyphenyl alpha-D-mannopyranoside via a dibutyltin intermediate gave p-methoxyphenyl 3-O-allyl-alpha-D-mannopyranoside (2) in good yield. Benzoylation (-->3), then removal of 1-O-methoxyphenyl (right arrow4), and subsequent trichloroacetimidation afforded the 3-O-allyl-2,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate (5). Condensation of 5 with methyl 4,6-O-benzylidene-alpha-D-mannopyranoside (6) selectively afforded the (1-->3)-linked disaccharide 7. Benzoylation of 7, debenzylidenation, benzoylation, and deallylation gave methyl 2,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->3)-2,4,6-tri-O-benzoyl-alpha-D-mannopyranoside (11) as the disaccharide acceptor. Coupling of 11 with (1-->2)-linked mannose disaccharide donor 17 or trisaccharide donor 21, followed by deacylation, furnished the target tetrasaccharide and pentasaccharide, respectively.     

New 11(15-->1)abeotaxane, 11(15-->1),11(10-->9)bisabeotaxane and 3,11-cyclotaxanes from Taxus yunnanensis

Chemical examination of the seeds of Chinese yew, Taxus yunnanensis Cheng et L. K. Fu resulted in the isolation of an 11(15-->1)abeotaxane, an 11(15-->1), 11(10-->9)bisabeotaxane and two 3,11-cyclotaxanes. The structures of these new taxoids were established as 13alpha-acetoxy-5alpha-cinnamoyloxy-11(15-->1)abeotaxa-4(20),11-diene-9alpha,10beta,15-triol (1), 20-acetoxy-2alpha-benzoyloxy-4alpha, 5alpha, 7beta, 9alpha, 13alpha-pentahydroxy-11(15-->1), 11(10-->9) bisabeotax-11-eno-10,15-lactone (2), 2alpha,10beta-diacetoxy-5alpha-cinnamoyloxy-9alpha-hydroxy-3,11 -cyclotax-4(20)-en-13-one (3) and 10beta-acetoxy-2alpha,5alpha,9alpha-trihydroxy-3,11-cyclotax-4(20)-en-13-one (4) on the basis of spectral analyses.     

Ambiguous genitalia by 9p deletion inherent to a dic(Y;9)(q12;p24)

We describe here a 3-month-old male infant with brachy-plagyocephaly, short neck, widely spaced nipples, mild hypertonia, and ambiguous external genitalia but with both testes in the scrotum and no Müllerian derivates. His karyotype was 45,X,der(Y;9)(q12;p24).ish der(Y;9)(DYZ3+,SRY+,9ptel-) de novo. This patient's impaired sex differentiation is consistent with gonadal dysgenesis and compares with the male-to-female sex reversal secondary to a partial 9p deletion in spite of an intact Yp or SRY locus documented in 24 patients including a sex-reversed girl with a (Y;9) dicentric derivative. As for the cytogenetic findings, this case represents the second instance of a de novo pseudodicentric (Y;9) chromosome with loss of both distal 9p and Yq12 regions, apparent intactness of SRY, and consistent or preferential inactivation of the Y centromere. In addition, the possible 9p23p-p22 duplication observed in this case evokes the concomitant 9p22-p21 duplication documented in the previous girl with a (Y;9) derivative. Hence, these striking similarities point to a nonrandom Y;9 rearrangement in patients with either sex reversal or gonadal dysgenesis. Even if the present pseudodicentric derivative had inactivated the Y centromere, the existence of some variant cells points to functional dicentricity as it has been documented in other Y;autosome dicentric derivatives.     

Partial trisomy 8p (8p11.2-->pTER) and deletion of 13q (13q32-->qTER): case report

We report a female infant with partial trisomy 8p (8p11.2-->pter) and deletion of 13q (13q32-->qter). She was born with mild hypotonia, intrauterine growth retardation, microcephaly, micrognathia, large low set ears, pectus excavatum, anteriorly placed anus, and bilateral clinodactyly. Echocardiography showed left ventricular hypertrophy, bicuspid aortic valve, dilatation of the aorta and pulmonary artery, and prolapse of atrio-venticular valve leaflets. Cytogenetic investigation of her sister and her father showed that the altered region resulted from a balanced translocation between the part of the long arm of chromosome 13 and short arm of chromosome 8. In partial trisomy 8p, the clinical picture of the patients comprises hypotonia, structural brain abnormalities, facial anomalies including a large mouth with a thin upper lip, a high arched palate, a broad nasal bridge, an abnormal maxilla or mandible, malformed, low set ears, and orthopedic anomalies. Although patients with proximal deletions of 13q that do not extend into band q32 have mild to moderate mental and growth delays with variable minor anomalies, patients with more distal deletions including at least part of band q32 usually have major malformations such as retinoblastoma, mental-motor growth retardation, malformation of brain and heart, anal atresia, and anomalies of the face and limbs. To our knowledge partial trisomy 8p and partial monosomy of 13q have not been reported previously in the same person.     

46,XX,der(2)t(2;10)(2pter-->2q37::10p13-->10pter)[127]/45,X,der(2)t(2;10) (2pter-->2q37::10p13-->10pter)[23]. Karyotype-phenotype correlation and genetic counselling in complex karyotypes

We describe a female child with complex cytogenetic anomalies consisting in partial trisomy of the short arm of chromosome 10, terminal deletion of the long arm of chromosome 2 and--at the same time--a mosaicism for X monosomy. To our knowledge, this is the first case reported in which 10p trisomy is associated to a 2qter deletion. Due to the scarcity of cases reported with pure trisomy, it has not been possible to define the 10p+ syndrome precisely yet. Comparison of our proband's phenotype to both the 2q37 deletion and 10p trisomy showed more features described in 2q37- subjects than in 10p+ ones. We also discuss the difficulties of genetic counseling in children with complex aberrations.     

Phenotypic and cytogenetic spectrum of 9p trisomy

Trisomy 9p is one of the most frequent autosomal anomalies compatible with long survival rate. The spectrum of clinical severity in trisomy 9 roughly correlates with the extent of trisomic chromosome material. Trisomy 9p is a clinically well delineated syndrome and of all stigmata craniofacial dysmorphism is most specific. In this study we report five cases with de novo trisomy 9p. The study aimed at the identification of the genotype/phenotype correlations in patients with different breakpoints. GTG banding, DAPI stain, whole chromosome paint, centromere, telomere and 9p21 specific locus probes demonstrated that partial trisomy 9p in case 1 was due to isochromosome 9p with translocation of the long arm of re-arranged chromosome 9 onto the short arm of chromosome 13, cases 2 and 3 had intrachromosomal duplication of the short arm of chromosome 9 [dup(9)(p21p24)], case 4 had "classical" 9p trisomy and case 5 had duplication of whole short arm and part of the long arm of chromosome 9 (partial 9 trisomy). Although cases 1 to 4 had trisomy involving 9p, cases 1 and 2 exhibited the classical clinical manifestations of 9p trisomy, while cases 3 and 4 had additional features overlapping with Coffin-Siris syndrome. The present study strengthens the association of Coffin-Siris syndrome and 9p, the significance of such observations may point to possible gene location of Coffin-Siris syndrome on 9p. Case 5 had additional manifestations more than those typical of trisomy 9p which could be due to duplication of 9q21 region. Wide gap between 1st and 2nd toes, observed in the studied cases, can be added to the phenotype of this trisomy. Three of our cases had brain malformations, case 3 had dilated ventricles with hypogenesis of corpus callosum, case 4 had agenesis of corpus callosum, and case 5 had Dandy-Walker malformation. We also suggest that dosage effects of genes located in 9pter-q22 contribute to the etiology of Dandy-Walker syndrome. We recommend MRI studies as a routine in all cases with trisomy 9p.     

Trisomy 9p in a girl whose mother has a translocation t(9;20)(q12;p13)

Summary R banding of the fine structure of the chromatids has enabled us to study a new case of trisomy for the short arm of chromosome 9. The syndrome+9p was due to nondisjunction of a maternal translocation t(9;20)(q12;p13).     

Tertiary trisomy of 10p15.pter and 14pter.ql3 due to maternal translocation t(10;14)(p15;q13)

Double partial trisomy resulting from 3:1 segregation of the respective chromosomal segments of the chromosomes involved in a balanced translocation in meiosis is rarely reported in the literature. We present here a first patient with multiple congenital malformations associated with double partial trisomy of 10pter-p15 and 14pter-q13 resulting from 3:1 segregation of maternal balanced translocation t(10;14)(p15;q13). Proximal partial trisomy of chromosome 14 and subterminal trisomy of the short arm of the chromosome 10 are rare. The present case is the first case with double partial trisomy of these segments resulting from 3:1 segregation of a maternal balanced translocation.     

Duplication 5q and deletion 9p due to a t(5;9)(q34;p23) in 2 cousins with features of Hunter-McAlpine syndrome and hypothyroidism

We report on 2 similarly affected cousins with a compound imbalance resulting from a familial t(5;9)(q34;p23) and entailing both an ～17-Mb 5q terminal duplication and an ～12-Mb 9p terminal deletion as determined by G-banding, subtelomere FISH, and aCGH. The proband's karyotype was 46,XX,der(9)t(5;9)(q34;p23)mat.ish der(9)t(5;9)(q34;p23)(9pter-,5qter+).arr 5q34q35(163,328,000-180,629,000)×3, 9p24p23(194,000-12,664,000)×1. Her cousin had the same unbalanced karyotype inherited from his father. The clinical phenotype mainly consists of a distinct craniofacial dysmorphism featuring microcephaly, flat facies, down slanting palpebral fissures, small flat nose, long philtrum, and small mouth with thin upper lip. Additional remarkable findings were craniosynostosis of several sutures, craniolacunia and preaxial polydactyly in the proband and hypothyroidism in both subjects. The observed clinical constellation generally fits the phenotypic spectrum of the 5q distal duplication syndrome (known also as Hunter-McAlpine syndrome), except for the thyroid insufficiency which can likely be ascribed to the concurrent 9p deletion, as at least 4 other 9pter monosomic patients without chromosome 5 involvement had this hormonal disorder. The present observation further confirms the etiology of the HMS phenotype from gain of the 5q35→qter region, expands the clinical pictures of partial trisomy 5q and monosomy 9p, and provides a comprehensive list of 160 patients with 5q distal duplication.     

Synthesis of beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->6)-[beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->3)]-beta-D-GlcpOLauryl, an oligosaccharide with anti-tumor activity

A concise and effective synthesis of lauryl heptasaccharide 17 was achieved from the key intermediates lauryl 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-beta-D-glucopyranosyl-(1-->3)-2,4-di-O-benzoyl-beta-D-glucopyranoside (10) and isopropyl 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-beta-D-glucopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-1-thio-beta-D-glucopyranoside (15). The key trisaccharide glycosyl acceptor 10 was constructed by coupling 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-alpha-D-glucopyranosyl trichloroacetimidate (3) with lauryl 6-O-acetyl-2,4-di-O-benzoyl-beta-D-glucopyranoside (9), followed by deacetylation. The thioglycoside donor 15 was obtained by condensation of 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (11) with isopropyl 4,6-O-benzylidene-1-thio-beta-D-glucopyranoside (12), followed by debenzylidenation and acetylation. A bioassay of the inhibition of S180 noumenal tumors showed that lauryl heptasaccharide 17 could be employed as a potential agent for cancer treatment.     

A severely mental and motor retarded boy with monosomy 9pter-->p22 trisomy 10q26-->qter due to paternal reciprocal translocation 46,XY,t(9;10)(p23;q26)

We report on a twenty-two months old male patient with hypotonia, mental and motor retardation and trigonocephaly. Standard GTG banding chromosomal analysis (from metaphyses of a periferal blood lymphocyte culture) showed 46,XY, der(9) monosomy 9pter-->p22, trisomy 10q26--> qter karyotype. This unbalanced translocation resulted from the father's t(9,10) (p22;p26) karyotype. Deletions of the terminal part of 9p and partial trisomy of chromosome 10q are rare chromosomal disorders. To our knowledge, this is the first case report in the literature of a deletion of 9pter-->p22.3 and a duplication of 10q26-->qter. We assume that the clinical anomalies are due to der(9) monosomy 9pter-->p22, trisomy 10q-->26qter.     

Molecular characterization of near-complete trisomy 17p syndrome from inverted duplication in association with cryptic deletion of 17pter

Trisomy of the short arm of chromosome 17 (T17P) is a genomic disorder presenting with growth retardation, motor and mental retardation and constitutional physical anomalies including congenital heart defects. Here we report a case of near-complete T17P of which the genomic dosage aberrations were delineated by chromosomal microarray along with conventional diagnostic modalities. A 9-year-old Korean boy was admitted because of esophageal obstruction. He showed clinical manifestations of T17P, along with atypical features of scoliosis, corpus callosum agenesis, and seizure. Chromosome analyses revealed an inverted duplication of the chromosomal segment between 17p11.2 and 17p13.3. Chromosomal microarray revealed a duplication of the most of the short arm of chromosome 17 (size ~ 19.09 Mb) along with a cryptic deletion of a small segment of 17p terminal end (17pter) (~ 261 Kb). This is the first report of molecular characterization of near-complete T17P from inverted duplication in association with 17pter microdeletion. The fine delineation of the extent of genomic aberration by SNP-based microarray could help us better understand the molecular mechanism and genotype–phenotype correlations in T17P syndrome.     

Type and contretype signs in monosomy and trisomy 9p. On a case 46,XY, del (9) (pter yields p12:).

A 15-month-old male with a partial monosomy 9p is reported. The comparative analysis with other cases of 9p monosomy demonstrates a typical phenotype which when compared to that of 9p trisomy, permits the delineation of fifteen "type and contretype" signs.     

Trisomy 9p with an isochromosome of 9p

An 18 1/2-year-old female is described with moderately severe mental retardation, the phenotype of the trisomy 9p syndromy, and an isochromosome for the short arm of a chromosome 9, contained in an unique karyotype, 46,XX,-9,t(7q9q),+ iso 9p.