9p Deletion and distal 9q duplication due to a paternal pericentric inversion 9(p22q32)

A female infant with 46,XX,rec(9), dup q,inv(9)(p22q32)pat is presented. She had a duplication from 9q32 to qter and a deletion from 9q22 to 9pter. Phenotypical abnormalities observed corresponded with features noted in cases with distal dup (9q), while pathognomonic features of del(9p) syndrome were not observed.     

Pericentric inversion of chromosome 16 in a large kindred: Spectrum of morbidity and mortality in offspring

Constitutional pericentric inversions of chromosome 16 are rare in the general population. We report here a large kindred who carry an inv(16)(p13q22) rearrangement. In general, individuals with the inv(16) are in good health but prone to reproductive loss. Two different types of recombinant offspring were identified in this family and analyzed at the molecular level using probes from the α-globin and polycystic kidney disease loci. Both were associated with serious major malformations. © 1992 Wiley-Liss, Inc.     

Pericentric inversion of chromosome 4 giving rise to dup(4p) and dup(4q) recombinants within a single kindred

Theoretically, every pericentric inversion can give rise, during meiosis, to 2 alternate recombinant chromosomes. One of these will have a duplication of short arm material and deletion of long arm material (dup p), and the other, a duplication of a long arm material and deletion of short arm material (dup q). However, most published cases have been limited to a single recombinant type occurring within a given kindred. Here we document a large pericentric inversion of chromosome 4 which gave rise, within 2 generations of a kindred, to both dup p and dup q recombinants. The family was ascertained by the birth of a baby girl with multiple congenital anomalies suggestive of Wolf-Hirschhorn syndrome, and was found to have a dup 4q recombinant. Subsequent studies of her father and of her 27-year-old mentally retarded aunt showed a balanced inv(4) (p15.32q35) and a dup 4p recombinant, respectively. Given that: (a) the balanced inversion involves approximately 87% of the length of chromosome 4; (b) the predicted meiotic pairing would be homosynapsis with loop formation; (c) the size of the segments distal to the breakpoints of the inversion are of similar and relatively small size; and (d) both recombinants are compatible with life, then the risk for recurrence of a recombinant in this family is high. Genetic counseling addressed these issues, and to date, both chronic villus sampling (CVS) and amniocentesis have been provided for prenatal diagnosis. © 1993 Wiley-Liss, Inc.     

Recombinant chromosome 18 resulting from a maternal pericentric inversion

We report on a newborn girl with duplication of 18q12.2→18qter and deficiency of 18p11.2→18pter which resulted from meiotic recombination of the maternal pericentric inversion, inv(18) (p11,2q12.2). Her clinical manifestations were compatible with those of partial trisomy 18q syndrome. We review the previously reported 9 cases in 8 families of rec(18) resulting from recombination of a parental pericentric inversion. © 1994 Wiley-Liss, Inc.     

Abnormalities resulting from a familial pericentric inversion of chromosome 18

A female infant is reported with duplication/deficiency of chromosome number 18 due to a familial pericentric inversion of chromosome 18. This patient had many of the classical findings of trisomy 18.     

Pericentric inversion, inv(9) (p22 q32), in the father of a child with a duplication-deletion of chromosome 9 and gene dosage effect for adenylate kinase-1

A pericentric inversion of chromosome 9 was detected in the father of a child with partial trisomy involving the long arms and partial monosomy of the short arms of chromosome 9. A gene dosage effect was demonstrated for adenylate kinase 1 in erythrocytes.     

Chromosome segregation in an infertile man carrying a unique pericentric inversion, inv(21)(p12q22.3), analysed using fluorescence in situ hybridization on sperm nuclei: significance for clinical genetics. A case report

We report the case of a 40-year-old patient referred to our centre after 3 years of infertility. Karyotyping with the aid of fluorescence in situ hybridization (FISH) analysis showed a unique pericentric inversion of chromosome 21:46,XY,inv(21)(p12q22.3). This type of intrachromosomal structural rearrangement can lead to chromosome imbalance in offspring by producing unbalanced gametes if an odd number of crossover events occur within the inverted segment. Therefore, partial trisomy/monosomy with clinical consequences can be observed in the progeny of carriers. Semen samples from the inversion carrier were analysed by FISH using a combination of probes [a subtelomeric 21q probe and a locus-specific Down's syndrome critical region (DSCR) probe] to evaluate the proportion of recombinant chromosomes. Sperm-FISH analysis of 3400 spermatozoa revealed a 67.4% rate of balanced chromosomes (normal or inverted). The frequencies of recombinant chromosomes with duplication of the long arm and deletion of the short arm, and vice versa, were 11.2 and 21.4%, respectively. The risk for the couple of conceiving a child with an unbalanced chromosome 21 is estimated to be around 32%. This case study shows the utility of sperm-FISH analysis in the genetic counselling of a pericentric inversion in a male carrier to assess the frequency of recombinant chromosomes and therefore evaluate the probability of having a normal conception.     

Paracentric inversion involving the long arm of chromosome 9 resulting in deletion of abl gene

We report on a new chromosomal finding in a newborn male with hypertelorism, apparently low-set malformed ears with patent canal, micrognathia with narrow high-arched palate, bilateral webbing of neck with low posterior hairline, widely spaced nipples, and complex heart anomalies. Initially, what appeared to be a simple paracentric inversion of the long arm of chromosome 9, that is, 46,XY, inv(9)(q31q34) by routine GTG-banding technique was later determined to be a paracentric inversion with deletion of the band 9q34.1 by FISH technique using an abl unique sequence DNA probe. Thus the cytogenetic diagnosis was modified to 46,XY,der(9) inv(9)(q31q34.1)del(q34.1). Nevertheless, the presence of telomeric repeat sequences in the inverted chromosome 9 suggests that either healing has occurred by adding [TTAGGG]_n sequences to the nontelomeric end (q31) by the enzyme telomerase or telomeric sequences were not affected during this inversion process. This abnormality is a rare occurrence and has never been reported before either because of a high rate of lethality or it has been undetected by routine cytogenetic techniques. The other abnormal cases with apparent paracentric inversions could also have a complex nature with congenital anomalies associated with loss of “few” DNA sequences as exemplified here. Am. J. Med. Genet. 68:409–411, 1997. © 1997 Wiley-Liss, Inc.     

Sapira SK,Orr-Urtreger A,Gagos S,Shaffer LG (1997): Constitutional mosaicism for a chromosome 9 inversion resulting in recombinant aneusomy in an offspring. Am J Med Genet 69:360-364

The abstract of the article referenced was published incorrectly. Below is the correct abstract. The publisher regrets this error.     

Study on segregation and risk for abnormal offspring in carriers of pericentric inversion of the (p11←q13) segment of chromosome 2

Pericentric inversion of chromosome 2 was detected in four unrelated families. All these inversions involved the segment p11←q13. The pedigree data are considered in comparison with other cases reported in the literature. Segregation data and possible reproductive failures are discussed.     

A pericentric inversion of chromosome 9 and a rearrangement involving chromosomes 9 and 10, observed in two generations. Clinical description of chromosome 9 (p12-p21) deletion syndrome

The clinical picture associated with a deletion of a central part of the short arm of chromosome no. 9 is described in two siblings. The clinical signs differ from those described in deletion of the terminal part of the short arm. Pericentric inversion of chromosome no. 9, combined with a rearrangement involving chromosomes 9 and 10, was found in the mother and the maternal grandmother of the propositus.     

Ullrich-turner syndrome (45,X/46,X,i[Xq]) in a child with a familial inversion of chromosome 3

We report a girl with shortness of stature and minor anomalies representing a mild form of the Ullrich-Turner syndrome. Cytogenetic studies showed 3 distinct anomalies: (1) a familial pericentric inversion, inv(3) (p25q21)pat, in all cells examined; (2) monosomy X (45,X) in 70% of cells; (3) isochromosome X (46,X,i(Xq)) in 30% of cells. The karyotype designation is: 45,X,inv(3) (p25q21)pat/46,X,i(Xq), inv(3) (p25q21)pat. The pedigree, which was originally interpreted as representing the segregation of a 2;3 translocation, is corrected and updated. Reproductive risks in families with pericentric inversions are discussed.     

Balanced complex rearrangement involving chromosomes 8, 9, and 12 in a normal mother,derivative chromosome 9 with recombinant chromosome 12 in her daughter with minor anomalies

We report on a 19-month-old girl with a derivative chromosome 9 and a recombinant chromosome 12 resulting from a maternal balanced complex rearrangement involving chromosomes 8, 9, and 12. The karyotype of the phenotypically normal mother was 46,XX,t(8;12) (9;12) (8qter→8p23::12q12→12q15::9q32→9qter;9pter→9q32::12q15→12qter;12pter→12q12::8p23→8pter). The child's karyotype was 46,XX,?9,?12, +der(9) (9pter→9q32::12q15→12qter),+rec(12) (12pter→12q15::9q32→9qter) mat. The child had severe growth retardation, minor anomalies including trigonocephaly, hypertelorism, broad nasal root, apparently low-set and posteriorly angulated ears, triangular face, pectus carinatum, clinodactyly of fifth fingers, and almost normal psychomotor development. To the best of our knowledge, there have been only 3 previous reports of recombination derived from parental complex chromosome rearrangements. In the recombination products, the chromosomes were apparently balanced and the offspring had no clinical abnormalities. The present case exhibited abnormalities and may have a submicroscopic aberration of 12q arising from crossing over during maternal meiotic pairing, although her chromosomes appeared to be balanced. © 1993 Wiley-Liss, Inc.     

Trisomy 9 syndrome: Report of a case with Crohn disease and review of the literature

We report on a 6-year-old boy with mosaic trisomy 9. The patient was born at 42 weeks of gestation to a 27-year-old G1 white woman. Birth weight was 2,820 g, length 52 cm, and Apgar scores were 4 and 6 at 1 and 5 min, respectively. The infant presented with apparently low-set ears, overfolded helices, epicanthal folds, prominent nasal bridge, high-arched palate, micrognathia, bilateral dislocated hips, left genu recurvatum, and cryptorchidism. Chromosome analysis showed an unusual karyotype: 47,XY,+inv(9qh+)/47,XY,+mar. The marker chromosome was thought to be a remnant of the inv(9qh+) chromosome. The mother's karyotype was 46,XX,inv(9qh+), while the father's was 46,XY. At age 5 months, the patient developed seizures and gastroesophageal reflux. Crohn disease was diagnosed at age 2 years, although symptoms began at age 1 year. Recurrent bouts of pneumonia have occurred since the patient's birth. Severe psychomotor retardation was also noted. Trisomy 9 syndrome was first reported in 1973. Over 30 cases have been reproted since then. Of these case reports, only 5 patients were older than 1 year. Inflammatory bowel disease has been reported in association with other chromosome abnormalities, but to our knowledge, has not been reported in trisomy 9 syndrome. © Wiley-Liss, Inc.     

Unusual cytogenetic mosaicism involving chromosome 14 abnormalities in a child with an MR/MCA syndrome and abnormal pigmentation

An 8-year-old female child with mental retardation (MR), multiple congenital anomalies (MCA) and irregular pigmentation was shown to have karyotypic mosaicism involving chromosome 14 abnormalities. Four cell lines were found in both peripheral blood lymphocytes and skin fibroblasts and were represented by: a normal karyotype, an isopseudodicentric 14q [iso psu dic(14)], a ring 14 [r(14)], and a monosomy 14 [mono(14)]. Our results are compared with reported cases involving multiple abnormalities of specific chromosomes. Karyotypic mosaicism of comparable chromosome 14 abnormalities is rare, with only one known previous case. Detailed analysis of karyotypic mosaicism of rare chromosomal abnormalities is essential to determine meaningful correlations with specific patterns of malformation.     

Mosaic trisomy 16 in a thriving infant; maternal heterodisomy for chromosome 16

Lindor NM, Jalal SM, Thibodeau SN, Bonde D, Sauser KL, Karnes PS. Mosaic trisomy 16 in a thriving infant; maternal heterodisomy for chromosome 16
Clin Genet 1993: 44: 185–189. © Munksgaard, 1993
Trisomy 16 is the most common trisomy in spontaneous abortions and is usually, if not always, lethal in the nonmosaic state. We report a liveborn infant with trisomy 16 mosaicism first diagnosed by amniocentesis at 20 weeks gestation. At birth, the infant was growth retarded and mildly dysmorphic. At age 14 months she was developmentally normal and had facial asymmetry. Her length, weight and head circumference were normal. Pure trisomy 16 was found in cells from the placenta. A normal female karyotype was found in lymphocytes from the infant. Skin fibroblasts revealed a trisomy 16 karyotype in 6 of 30 cells. Molecular analysis showed maternal uniparental heterodisomy, indicating that the trisomic conceptus arose from a nondisjunction of maternal meiosis. Fibroblasts may be the tissue of choice for detection of low-level trisomy 16 mosaicism.