Partial trisomy 8q and partial monosomy 18p: a case report

We report clinical observations and cytogenetic studies of an inherited partial trisomy 8q and partial monosomy 18p. A full trisomy 8 syndrome (Warkany syndrome) is a clinically recognized syndrome. Partial trisomy 8q has been reported sporadically in the literature with variable phenotypes. Partial monosomy 18p, deletion of the short arm of chromosome 18, is also a well-recognized syndrome. This is the first report to the best of our knowledge of partial trisomy for distal 8q and partial monosomy for distal 18p occurring together in a patient.     

Partial trisomy of distal 5q and partial monosomy of Xp as a result of mating between two translocation carriers: a female with a balanced translocation t(X;5)(p11;q31) and a male with a der(13;14)(q10;q10)--a case report and a family study

This paper presents the family of a dysmorphic child with the phenotypic features of Turner's syndrome and 5q trisomy, whose parents are both carriers of a balanced translocation. The parents' karyotypes are 46,X,t(X;5)(p11.1;q31) and 45,XY,der(13;14)(q10;q10), respectively.     

Partial trisomy 18q11.2-->qter due to de novo unbalanced translocation of chromosomes 15 and 18 analyzed by fluorescence in situ hybridization

This report presents a case with partial trisomy 18q resulting from de novo unbalanced translocation of chromosomes 15 and 18 displaying the features of pure trisomy. This is the first reported case with partial trisomy 18q due to unbalanced translocation between chromosomes 15 and 18. Clinical findings of our case have been compared with the reported cases' had partial trisomy 18q and the importance to recognize the cases with chromosome abnormalities to give genetic counseling and prenatal diagnosis for subsequent pregnancies has emphasized.     

Severe psychomotor retardation in a boy with a supernumerary derivative chromosome resulting in partial trisomy 21 and partial trisomy 7p

We report on a 12-year-old boy with a supernumerary chromosome der(21)t(7; 21)(p21; q21.3)mat, resulting in a partial trisomy 21 and a partial trisomy 7p. The patient has a severe psychomotor retardation. Although he has most of chromosome 21 in three copies, he does not have a phenotype of Down syndrome (DS). In addition to cytogenetic analysis, molecular analysis confirmed that the "DS critical region" on chromosome 21 (21q22) is not present in three copies, since the breakpoint of the partial trisomy 21 was found to be located distal to the marker locus D21S145 but proximal to D21S226. The patient's severe mental retardation is probably due to the small telomeric 7p trisomy, having the breakpoint between markers D7S507 and D7S488. In comparison with previously published cases of partial trisomy 7p, the phenotype of this patient indicates that there is a region around the distal part of band 7p21 that in three copies might contribute to many of the facial features common to patients with partial trisomy 7p.     

Prenatal diagnosis of de novo partial trisomy 18p and partial monosomy 18q recurrent in a family with fatal aortic coarctation

Aortic coarctation is a life-threatening defect when it occurs with cardiorespiratory failure. Its genetic cause remains unknown. A woman was pregnant twice, both with male fetuses that had partial trisomy 18p, partial monosomy 18q, and aortic coarctation. The syndrome may relate to the aortic coarctation and pulmonary hypoplasia and is life-threatening. ArrayCGH analysis suggested a de novo 17.7 Mb deletion of chromosome 18q21.33 → qter (58,413,193 bp to 76,116,029 bp) and a de novo 12.4 Mb duplication of chromosome 18pter → p11.21 (1543 bp to 12,438,430 bp) at the telomeric end of chromosome 18. To the best of our knowledge, the present chromosomal breakpoint with rearrangement has not been previously described. This chromosome aberration may be responsible for this syndrome.     

De novo partial trisomy 18p and partial monosomy 18q in a patient with anorectal malformation

Anorectal malformations (ARM) encompass a broad clinical spectrum which ranges from mild anal stenosis to severe anorectal anomalies such as complex cloacal malformations. The overall incidence of ARM is around 1 in every 2,500 live births. Although causative genes for a few syndromic forms have been identified, the molecular genetic background of most ARM remains unknown. The present report describes a patient with a de novo 13.2-Mb deletion of chromosome 18q22.3-qter and a 2.2-Mb de novo duplication of chromosomal region 18pter-p11.32 located at the telomeric end of chromosome 18q. The patient presented with ARM and the typical features of 18q- syndrome (De-Grouchy syndrome). The combination of a partial duplication of the short arm and a partial deletion of the long arm of chromosome 18 has been described in 16 previous cases. However, this is the first report of an association between this complex chromosomal rearrangement and ARM.     

Monosomy 9pter and trisomy 9q34.11qter in two sisters due to a maternal pericentric inversion

Pericentric inversions of chromosome 9 leading to unbalanced live-born offspring are relatively rare and so far only four cases have been reported. Here we present two sisters with an unbalanced recombinant chromosome 9 which resulted from a large maternal pericentric inversion inv(9)(p24.3q34.1). Further molecular characterisation of the aberrant chromosome 9 by 250k SNP array analysis showed a terminal 460 kb loss of 9p24.3 and a terminal 8.9 Mb gain of 9q34.11. We compared the clinical features of these two patients with the previous reported four cases as well as with patients with similar sized 9pter deletions or 9qter duplications. Based upon this study, we suggest that the recombinant chromosome 9 phenotype is mainly the result of duplication of a 3.4 Mb region of chromosome 9q34.11q34.13.     

"Cri-du-chat" syndrome in a patient born to a mother with a paracentric inversion of chromosome 5q

We report the case of a female child presented at birth with hypotonia, growth retardation and respiratory distress. Chromosome study from peripheral blood showed a 46,XX,del(5)(p14pter) karyotype. Parental chromosome studies revealed that the mother carried an apparently balanced paracentric inversion of long arms of one chromosome 5, giving the karyotype 46,XX,inv(5)(q12q32), whereas paternal karyotype was normal. The maternal abnormality was confirmed by fluorescence in situ hybridization (FISH) and was not present in the daughter's metaphases. Microsatellite analysis in the proposita and her parents permitted us to conclude that the deleted chromosome 5 was paternal in origin, as usually described. Therefore, as might have been expected, maternal paracentric inversion of chromosome 5q and "cri-du-chat syndrome" presented by the daughter were not related.     

Proximal trisomy 13q and distal monosomy 8p in a dysmorphic and mentally retarded patient with an isodicentric chromosome 13q and a 13q/8p translocation chromosome

A 40 year-old dysmorphic and mentally retarded female is reported with a de novo unbalanced chromosomal rearrangement (karyotype: 46,XX,der(8)t(8;13)(p23;q123),idic(13)(pter-->q123: q123-->pter) resulting in an isodicentric chromosome 13 and a double aneusomy including partial trisomy 13 (13pter-q123) and distal monosomy 8p (8pter-p23). The main clinical findings consist of developmental/mental retardation, behavioural disturbances and minor congenital defects, not consistent with the clinical pattern of either of the two aneusomies. A mechanism for the chromosome rearrangement is proposed and the absence of specific physical findings in the present patient is discussed in the light of the available literature data.     

Multiorgan autoimmunity in a Turner syndrome patient with partial monosomy 2q and trisomy 10p

Turner syndrome is a condition caused by numeric and structural abnormalities of the X chromosome, and is characterized by a series of clinical features, the most common being short stature and gonadal dysgenesis. An increased frequency of autoimmune diseases as well as an elevated incidence of autoantibodies has been observed in Turner patients.     

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.     

Duplication of CXC chemokine genes on chromosome 4q13 in a melanoma-prone family

Copy number variations (CNVs) have been shown to contribute substantially to disease susceptibility in several inherited diseases including cancer. We conducted a genome-wide search for CNVs in blood-derived DNA from 79 individuals (62 melanoma patients and 17 spouse controls) of 30 high-risk melanoma-prone families without known segregating mutations using genome-wide comparative genomic hybridization (CGH) tiling arrays. We identified a duplicated region on chromosome 4q13 in germline DNA of all melanoma patients in a melanoma-prone family with three affected siblings. We confirmed the duplication using quantitative PCR and a custom-made CGH array design spanning the 4q13 region. The duplicated region contains 10 genes, most of which encode CXC chemokines. Among them, CXCL1 (melanoma growth-stimulating activity α) and IL8 (interleukin 8) have been shown to stimulate melanoma growth in vitro and in vivo. Our data suggest that the alteration of CXC chemokine genes may confer susceptibility to melanoma.     

Partial trisomy 7q and probable partial monosomy of 5p in the son of a mother with a reciprocal translocation between 5p and 7q

Summary An underweight male newborn revealed a complex pattern of abnormal findings including severe neurologic dysfunction, a catlike cry, defective ossification of the calvarian bones, hypertelorism, downward slanting palpebral fissures, epicanthal folds, a short and flat nose with a flattened bridge, broad thumbs, clenched fingers 3–5 on the right hand, simian creases, a congenital heart defect, internal hydrocephalus, and bilateral hydronephrosis. He died on day 26 of his life. Chromosome examination disclosed a maternally inherited reciprocal translocation between 5p and 7q, resulting most probably in monosomy of 5q15 and trisomy of 7q32qter (46,XY, der (5), t(5;7)(p15;q32)mat).     

Molecular analysis of recombination in a family with Duchenne muscular dystrophy and a large pericentric X chromosome inversion.

It has been demonstrated in animal studies that, in animals heterozygous for pericentric chromosomal inversions, loop formation is greatly reduced during meiosis. This results in absence of recombination within the inverted segment, with recombination seen only outside the inversion. A recent study in yeast has shown that telomeres, rather than centromeres, lead in chromosome movement just prior to meiosis and may be involved in promoting recombination. We studied by cytogenetic analysis and DNA polymorphisms the nature of meiotic recombination in a three-generation family with a large pericentric X chromosome inversion, inv(X)(p21.1q26), in which Duchenne muscular dystrophy (DMD) was cosegregating with the inversion. On DNA analysis there was no evidence of meiotic recombination between the inverted and normal X chromosomes in the inverted segment. Recombination was seen at the telomeric regions, Xp22 and Xq27-28. No deletion or point mutation was found on analysis of the DMD gene. On the basis of the FISH results, we believe that the X inversion is the mutation responsible for DMD in this family. Our results indicate that (1) pericentric X chromosome inversions result in reduction of recombination between the normal and inverted X chromosomes; (2) meiotic X chromosome pairing in these individuals is likely initiated at the telomeres; and (3) in this family DMD is caused by the pericentric inversion.     

Identification and characterization of a novel gene disrupted by a pericentric inversion inv(4)(p13.1q21.1) in a family with cleft lip

Cleft lip with or without cleft palate is a common birth defect affecting 1 in every 700 live births. Several genetic loci are believed to be involved in the pathogenesis of syndromic and non-syndromic clefting. We identified a pericentric inversion of chromosome 4, inv(4)(p13q21) that segregates with cleft lip in a two-generation family. By using a combination of fluorescence in situ hybridization, yeast artificial chromosome, bacterial artificial chromosome contig mapping, and database searching we mapped and sequenced the inversion breakpoint region. The pericentric inversion disrupts a gene (ACOD4) on chromosome 4q21 that codes for a novel acyl-CoA desaturase enzyme. The 3.0 kb human ACOD4 cDNA spans approximately 170 kb and is composed of five exons of ACOD4. The inversion breakpoint is located in the second exon. The 3.0 kb mRNA is expressed at high level in fetal brain; a lower expression level was found in fetal kidney. No expression of ACOD4 was detected in fetal lung or liver or in adult tissues. The five exons code for a protein of 330 amino acids, with a predicted molecular weight of 37.5 kDa. The protein is highly similar to acyl-CoA desaturases from Drosophila melanogaster to Homo sapiens. The catalytically essential histidine clusters and the potential transmembrane domains are well conserved.     

A submicroscopic unbalanced subtelomeric translocation t(2p;10q) identified by fluorescence in situ hybridization: fetus with increased nuchal translucency and normal standard karyotype with later growth and developmental delay, rhombencephalosynapsis (RES)

Reaching an accurate diagnosis in children with mental retardation associated or not with dysmorphic signs is important to make precise diagnosis of a syndrome and for genetic counseling. A female case with severe growth and development delay, dysmorphic features and feeding disorder is presented. Antenataly, the fetus was observed to have increased nuchal translucency and a slight hypoplastic cerebellum. A standard karyotype was normal. RES and a submicroscopic unbalanced subtelomeric translocation t(2p; 10q) were demonstrated after birth. We show that within the framework of a collaborative approach, a concerted research of submicroscopic subtelomeric rearrangements should be performed in case of mental retardation associated with facial dysmorphic features, and when other etiologies or non-genetic factors (iatrogenic, toxic, infectious, metabolic...) have been ruled out.     

Meiotic analysis of a pericentric inversion, inv(7) (p22q32), in the father of a child with a duplication-deletion of chromosome 7

In a family in which a large pericentric inversion of chromosome 7 is segregating, two of the four progeny of inversion heterozygotes show severe psychomotor retardation and have the karyotype 46,XX,rec(7),dup q,inv(7)(p22q32), derived from crossing-over within the inversion. Meiotic analysis in one of the heterozygotes revealed no evidence of inversion loops in well-spread pachytene cells. In approximately 20% of cells in diakinesis, the presumptive bivalent 7 had only one chiasma. Two alternatives to the reversed loop mode of meiotic pairing of inversions are proposed. Review of the literature supports the view that "small" pericentric inversions have a much better genetic prognosis than "large" pericentric inversions.     

Partial trisomy 7q and monosomy 13q in a child with disorder of sex development: Phenotypic and genotypic findings

Terminal 7q duplication and terminal 13q deletion are two conditions with variable phenotypes including microcephaly, thumb a-/hypoplasia, cortical dysplasia, microphtalmia, intellectual disability and dysmorphic features. We describe a boy born to a mother with a reciprocal t (7;13) who combines both a terminal 7q33-qter duplication and terminal 13q33-qter deletion through the inheritance of a derivative chromosome 13 (der (13)). The patient presented with developmental delay, facial and non-facial dysmorphic features, hypertonia, genital abnormality and skeletal malformation but no thumb a-/hypoplasia or microphtalmia. Knowing the exact breakpoints of his chromosomal aberrations using high resolution array CGH (aCGH) and comparison of his phenotypes with those of 24 and 59 previously published cases of 7q duplication and 13q deletion, respectively, allow us to further narrow the size of the proposed critical regions for microcephaly, thumb a-/hypoplasia and hypo/hypertonia on chromosome 13.     

11q Aneuploidy: Partial monosomy and trisomy in the children of a mother with a t(3;11)(p27;q23) translocation

Summary A woman with a balanced translocation t(3;11)(p27;q23) has had three abnormal children. The first child died in infancy, and of the two survivors who show segregation of the derivative maternal translocated chromosomes, one exhibits partial trisomy 11q and the other partial monosomy 11q. The two cases are compared with each other and with reported examples. Moreover, 11q break points are discussed.     

A de novo 3p13 deletion induced by a complex chromosomal rearrangement combined with a pericentric inversion of chromosome,inv(3)(p13q12), and a translocation between chromosome 3 and 8, t(3;8)(q13.1;q24.2), in a child with developmental delay

A de novo complex chromosomal rearrangement is very rare but likely to be present in a child with developmental disabilities and physical alterations. A child presented in this study showed global developmental delay and some typical phenotypes. Initial karyotyping and FISH analysis in the patient showed an apparently de novo balanced translocation between chromosome 3 and 8, t(3;8)(q13.1;q24.2). Further analysis using multiplex ligation-dependent probe amplification and array-based comparative genomic hybridization revealed a cryptic microdeletion on 3p13 region. Nearly one-third of balanced rearrangements are reported to involve cryptic disruptions at breakpoints, however, the microdeletion of the proposita was present in non-translocated region of the chromosome 3. After careful reevaluation of the results, a pericentric inversion, inv(3)(p13q13.1) that induced deletion was revealed. The clinical features of developmental delay in cognition, language, and motor function and facial and physical phenotype of the proposita were similar to those found in the children with 3p13 deletion. This case shows that combined molecular cytogenetic techniques with routine karyotyping are very useful to identify subtle genomic changes associated with abnormal phenotypes.