Familial pericentric inversion of the X chromosome [inv(X)(p11q28)]

A familial pericentric inversion of the X chromosome [46,X,inv(X)(p11q28)] and [46,inv(X)(p11q28), Y] is reported. The carriers of the inv(X) presented no clinical symptoms. Either the inverted or the normal X chromosome may be late replicating.     

Familial pericentric inversion (3)(p12q24)

Summary A large kindred with a familial pericentric inversion of chromosome 3, (p12q24), was found after an investigation initiated by a young female with three spontaneous first-trimester abortions. Altogether 22 (33%) inversion carriers were discovered, 9 females and 13 males. 6 women and 9 men were included in the fertility and segregation analyses because they were all either sexually mature or past maturity. The abortion frequency was below the average European rate in both the inversion carrier group and the cytogenetically normal relative group; 6%: 3%, respectively. The mean numbers of pregnancies and live births (1.8–3.1) did not vary significantly in the two comparison groups. The segregation analysis among the inversion carriers showed a good correspondence to the theoretical 11 ratio (1613). Males and females contributed equally. No duplication/deletion syndromes have been found in the kindred; all family members are phenotypically normal. We report a balanced familial pericentric inversion with no adverse effects. This chromosome aberration could be an example of a harmless chromosome polymorphism.     

Chromosome 3 duplication q21 leads to qter deletion p25 leads to pter syndrome in children of carriers of a pericentric inversion inv(3) (p25q21).

Close phenotypic similarity between two cases carrying a rec(3) dup q,inv(3) (p25q21), 12 additional infants from the same inv (3)(p25q21) kindred who lived less than 1 year, and eight cases studied in other medical centers has led us to postulate the existence of a distinct chromosome 3 duplication-deletion syndrome. In the presence of trisomy for (3)q21 leads to qter and monosomy for (3)p25 leads to pter, the facial dysmorphy is unique: a distorted head shape due to irregular cranial sutures, thick low eyebrows, long eyelashes, persistent lanugo, distended veins on the scalp, hypertelorism, oblique palpebral fissures, a very short nose with a broad depressed bridge and anteverted nares, protruding maxilla, thin upper lip, micrognathia, low-set ears, and a short webbed neck. Port-wine stains, congenital glaucoma, cloudy corneas, cleft palate and harelip also occur frequently. Each infant has difficulty sucking and swallowing. Congenital anomalies of the cardiovascular system, of midgut rotation, and of the urogenital system are noted for the infants who died neonatally. Most frequent is a ventricular septal defect, followed by atrial septal defect, patent ductus arteriosus, patent foramen ovale, and coarctation of the aorta. Omphalocele, umbilical hernia, hyperplastic kidneys, polycystic kidneys, double ureter, hydro-ureter, hydronephrosis, and undescended testes often occur. The extremities are short in proportion to the length of the trunk. Clinodactyly, coxa valga, talipes, and spina bifida are frequently observed.     

Chromosome segregation in a man heterozygous for a pericentric inversion, inv(9)(p11q13), analyzed by using sperm karyotyping and two-color fluorescence in situ hybridization on sperm nuclei

Analysis of sperm karyotypes and two-color fluorescent in situ hybridization (FISH) on sperm nuclei were carried out in a man heterozygous for the pericentric inversion inv(9)(p11q13). Sperm chromosome complements were obtained after in vitro fusion of zona-free hamster oocytes and donor sperm. A total of 314 sperm complements was analyzed: 153 (48.7%) carried the inverted chromosome 9 and 161 (51.3%) carried the normal one. None of the sperm complements contained a recombinant chromosome 9, suggesting that no chiasmata were formed in the heterochromatic region. The frequency of structural chromosome aberrations unrelated to the inversion (8.3%) and the frequency of conservative aneuploidy (3.2%) were within the limits observed in our control donors. The proportions of X-bearing (47.3%) and Y-bearing sperm (52.7%) were not significantly different from the expected 1:1 ratio. The percentage of disomy for chromosome 21 was analyzed by two-color FISH in 10 336 sperm nuclei. The disomy rate for chromosome 21 (0.30%) was not significantly different from that found in our controls. These results suggest that the risk for this man of producing chromosomally abnormal offspring or spontaneous abortions was not increased, and do not support the existence of an interchromosomal effect for chromosome 21. Received: 28 October 1996     

Two Down syndrome patients with rec(21),dupq,inv(21)(p11;q2109) from a familial pericentric inversion

Aneusomie de recombinaison arose from a familial pericentric inversion of a chromosome 21. Two female patients had a typical Down syndrome; one of them had slight psychomotor retardation. There was partial trisomy 21q2109----qter in these two patients but ZnCu SOD activity was normal.     

Pericentric inversion inv(7)(p11q21.1): report on two cases and genotype-phenotype correlations

We report on two unrelated cases of pericentric inversion 46,XY,inv(7)(p11q21.1) associated with distinct pattern of malformation including mental retardation, development delay, ectrodactyly, facial dismorphism, high arched palate. Additionally, one case was found to be characterized by mesodermal dysplasia. Cytogenetic analysis of the families indicated that one case was a paternally inherited inversion whereas another case was a maternally inherited one. Molecular cytogenetic studies have shown paternal inversion to have a breakpoint within centromeric heterochromatin being the cause of alphoid DNA loss. Maternal inversion was also associated with a breakpoint within centromeric heterochromatin as well as inverted euchromatic chromosome region flanked by two disrupted alphoid DNA blocks. Basing on molecular cytogenetic data we hypothesize the differences of clinical manifestations to be produced by a position effect due to localization of breakpoints within variable centromeric heterochromatin and, alternatively, due to differences in the location breakpoints, disrupteding different genes within region 7q21-q22. Our results reconfirm previous linkage analyses suggested 7q21-q22 as a locus of ectrodactily and propose inv (7)(p11q21.1) as a cause of recognizable pattern of malformations or a new chromosomal syndrome.     

Cytogenetic analysis of sperm from a man heterozygous for a pericentric inversion, inv (3) (p25q21).

Human sperm chromosomes were studied in a man heterozygous for a pericentric inversion of chromosome 3(p25q21). The pronuclear chromosomes were analyzed after in vitro penetration of golden hamster eggs. A total of 144 sperm were examined: 69.2% were chromosomally balanced and 30.8% were recombinant. Of the balanced complements, the proportion with a normal chromosome 3 (37.6%) was approximately equal to the proportion with an inverted 3 (31.6%). Of the recombinant complements, the proportion of sperm with a duplication q/deletion p (17.3%) was approximately equal to the reciprocal event of duplication p/deletion q (13.5%). The recombinant chromosome 3 with a duplication q and deletion p has been observed in several abnormal children, but the duplication p/deletion q has never been reported. My results demonstrate that both recombinant chromosomes are produced as expected from an unequal number of crossovers within an inversion loop. In all likelihood the duplication p/deletion q chromosome is an early embryonic lethal because of the amount of genetic material deleted. The proportions of X-bearing (48.9%) and Y-bearing sperm (51.1%) were not significantly different from the expected 1:1 ratio. There was no evidence for an interchromosomal effect. Of the three inversions studied by human sperm chromosome analysis, recombinant chromosomes have been observed only in this case.     

Pericentric inversion of chromosome 2 (p11 q13) in unrelated families (author's transl)]

A pericentric inversion of chromosome 2 has been detected in 4 unrelated families. The break points are identical in band 2p11 and band 2q13. Reproductive history of these couples is analyzed. The pathology of these particular regions of chromosome 2 is discussed.     

Recombination aneusomy of subtelomeric regions of chromosome 5, resulting from a large familial pericentric inversion inv(5)(p15.33q35.3)

We present a family with three cases of recombination aneusomy rec(5)dup(5q) originating from a large parental pericentric inversion of chromosome 5. The proband--a 6-year-old girl with mental retardation, speech delay, microcephaly, and slight facial dysmorphism--was referred for subtelomere testing. FISH with a Multiprobe Chromoprobe T System (CytoCell) and with several BAC clones mapping to both subtelomere regions of chromosome 5, revealed a recombinant chromosome rec(5)dup(5q) originating from a paternal pericentric inversion inv(5)(p15.33q35.3). The same inversion was present in the proband's father's twin-brother and rec(5)dup(5q) was also identified in his two mentally retarded daughters. The distance of breakpoints from the telomere was: 0.234-1.4 Mb for 5p and 4.1-4.8 Mb for 5q. HR-CGH analysis confirmed the duplication of the 5q subtelomeric region but did not identify any concomitant deletion in the 5p subtelomere. Precise mapping of the aneusomic regions in the proband enabled mapping the cat cry and speech delay to 5p15.33, making the earlier localizations of these features more precise. Our family shows that the large pericentric inversion with both breakpoints at subtelomeric regions of chromosome 5 is associated with a high risk of rec(5)dup(5q) in the progeny.     

Electron microscopic investigations of synaptonemal complexes in an infertile human male carrier of a pericentric inversion inv(1)(p32q42)

Summary Electron microscopic investigations of surface spread synaptonemal complexes in spermatocytes from a 37-year-old man ascertained for infertility detected a pericentric inv(1), and subsequent lymphocyte analysis placed the break-points at p32 and q42. Most spermatocytes showed a maturation arrest at mid-pachytene explaining the azoospermia. As in two other comparatively large loop-forming pericentric inversions, initiation of synapsis took place in the middle of the inverted segment. Thus there is no indication of interstitial synaptic initiation being restricted to special pairing sites along the length of the chromosome. All spermatocytes investigated at mid-pachytene showed inversion loops, none of which was fully synapsed with a specific delay in pairing of the heterochromatic block 1qh and adjacent segments. The loops were of similar size in all the cells examined and synaptic adjustment had not taken place. There was no indication of a preferential association between the inv(1) bivalent and the XY configuration, and a functional disturbance of the X seems an unlikely reason for the meiotic maturation arrest. The most likely cause may be the failure of adequate synapsis of the inverted segment and the possibly associated pairing abnormalities of other homologues, including asynapsis and/or precocious desynapsis.     

Complex translocation t(9;21)(9;22)(q12p13)(q12q11) in the family of a child with 9p trisomy syndrome

Summary Leukocyte peroxidase activity was estimated in 5 patients with the juvenile form of neuronal ceroid lipofuscinosis (Spielmeyer-Vogt's disease) and in 15 healthy controls. In contradiction to recent reports normal activity of p-phenylene diamine mediated peroxidase was found in the patients. The possible role of contamination of the white cell preparation with hemoglobin is discussed.     

Six cases of partial duplication-deficiency 21 syndrome: 21(dupq22delp23) due to maternal pericentric inversion: inv(21)(p12;q22). A family study

Six probands, apparently not related, with a minimal phenotype of Down's syndrome were investigated between 1970 and 1984 in our laboratory. We found in all of them an identical chromosomal abnormality 46,XX or XY,-21,+ der21(dupq22delp23). The der 21 was due to aneusomie de recombinaison, each mother having an abnormal chromosome 21: inv(21)(p12;q22). The fathers' caryotypes were normal. All parents were young and healthy. Pedigrees were established in order to find a relationship between these families. Four of our probands could be related. Familial investigations are still in progress for the last two cases; the ancestors being born in the same small geographical area (within 50 km2) we think that we shall be able to establish a relationship with the others families.     

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.     

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.     

Prenatal detection of a paracentric inversion 16(q11.2q13)

We report the prenatal detection of an inherited paracentric inversion 16(q11.2q13).     

inv(13)(p12;q14)一家系报道

先证者,女,汉族,２４岁,身高１．６１米,体重６０．１公斤。因连续生两胎畸形儿夭折就诊。第一胎为足月顺产,唇裂、腭裂、双足各为６趾,５０天时因呼吸道感染而死亡。第二胎,足月顺产,体征似第一胎,生下两天死亡。对先证者进行外周血染色体检查,计数５０个细胞...     

Novel variant Ph translocation t(9;22;11)(q34;q11.2;p15)inv(9)(p13q34) in chronic myeloid leukemia involving a one-step mechanism

Chronic myeloid leukemia (CML) is a clonal malignant disorder of a pluripotent hematopoietic stem cell characterized by the presence of a Philadelphia (Ph) chromosome. Less than 10% of patients present variant Ph chromosomes involving 1 or more additional chromosomes, other than chromosomes 9 and 22, with uncertain prognosis. There are mainly 1- or 2-step mechanisms proposed to explain the genesis of variant Ph chromosomes depending on whether the involved chromosomes are simultaneously broken and rejoined or if a standard t(9;22) occurs first. By combined standard cytogenetic and FISH analysis we detected a novel variant Ph translocation among chromosomes 9, 11 and 22 in a patient with CML without progression to an accelerated phase of the disease after 7 years, with the derivative chromosome 9 also having an acquired pericentric inversion. This novel case illustrates the use of FISH in metaphase to confirm a new rearrangement not previously described in variant Ph formation and that the present karyotype could have originated by a 1-step mechanism with 4 simultaneous breakages without deletion of ABL1.     

Recurrent proximal 18p monosomy and 18q trisomy in a family with a maternal pericentric inversion of chromosome 18

We report a recurrent partial monosomy of 18p10-->11.2 and proximal partial trisomy of 18q10-->21.3 caused by a maternal pericentric inversion of chromosome 18, involving breakpoints p11.2 and q21q21.3 Based on cytogenetics and FISH analysis, we speculate that the recurrent chromosome abnormality in the proband and in the fetus was the result of a translocation, possibly in a germ cell or germ cell precursor, between the maternal normal 18 and her inverted 18, resulting in maternal germinal mosaicism, i.e. 46,XX,inv(18)/46,XX,t[18;inv(18)][q10;q10]. The unbalanced karyotype of the proband and the fetus is 46,XY,+18,der[18;inv(18)][q10;q10]. To the best of our knowledge, there are no reports of this combination of proximal 18p monosomy and proximal 18q trisomy. The other interesting observation was association of Hirschsprung's disease in the proband.