Mosaic chromosome 18 anomaly delineated in a child with dysmorphism using a three-pronged cytogenetic techniques approach: a case report (original) (raw)
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An Indian diagnostic laboratory case report on mosaic chromosome 18
International Journal of Scientific Reports
Distal 18q deletion syndrome, and ring chromosome 18 are structural abnormalities involving chromosome 18. Distal or terminal deletion event is characterized by deletion of a region from the terminal end of a chromosome, while in ring chromosome, the telomeric ends of both the arms of homologous chromosomes are lost, causing the sticky ends to fuse together to form a ring. Clinical findings vary in each case depending on the type of abnormality, and the region of chromosome affected. This case report focuses on the chromosome 18 abnormality detected in the proband tested with the clinical indication of cleft lip, congenital anomaly, and feeding difficulty. Parental karyotyping to rule out de-novo or abnormality due to inheritance, clinical correlation, genetic counseling and high resolution microarray was recommended.
Cytogenetic investigation of a child with a mosaic isochromosome 18q and ring 18q
European Journal of Medical Genetics, 2007
We report on a baby girl from non-consanguineous Palestinian parents with intrauterine growth retardation, low birth weight, and developmental delay. She had a short stature, microcephaly, a prominent metopic suture, a glabellar haemangioma, exophthalmos, hypertelorism, upslanting palpebral fissures, horizontal nystagmus, flat nose, cleft lip and palate, a short neck, widely spaced nipples, umbilical hernia, flexion deformity of the wrist, ulnar deviation of fingers, and right club foot. Cortical atrophy, enlarged ventricles, a thin corpus callosum, thoracic hemivertebrae, and a ventricular septal defect were detected as well. High resolution chromosome analysis identified in 92% of cells an isochromosome 18 and in 8% of cells a ring 18. Molecular cytogenetic investigations confirmed that it was an i(18q) and a r(18q). The hypothesis to account for this anomaly and its corresponding phenotype are discussed.
American Journal of Medical Genetics, 2003
Isopseudodicentric chromosome 18 is very rare and results in a combination of partial trisomy and partial monosomy of chromosome 18. We report here a hypotrophic newborn with a lateral cleft lip and palate and multiple craniofacial dysmorphisms, a combined heart defect, unilateral hypoplasia of the kidney, bilateral aplasia of thumbs, and generalized contractures. Cytogenetic analysis revealed an isopseudodicentric chromosome 18 with breakpoint in 18q (46,XX,psu idic(18)(pter ! q22.1::q22.1 ! pter)). The isopseudodicentric chromosome 18 was observed in 100% of blood lymphocytes and umbilical cord fibroblasts, thus indicating a non-mosaic finding of the isopseudodicentric chromosome in the child. An elongated derivative chromosome 18 had also been found prenatally in amniotic cells. In contrast, a terminal deletion (18qÀ) was detected in placental cell cultures. The breakpoint was mapped to a 0.9 Mb region on 18q22.1 (located 64.8-65.7 Mb from the telomere of the p-arm) by a novel quantitative PCR approach with SYBR green detection. The results indicate an identical breakpoint of the isopseudodicentric chromosome 18 in the child and the 18qÀ chromosome in the placenta. To our knowledge this is the first report that a fetus carrying an isopseudodicentric chromosome 18 with breakpoint in 18q (46,XX,psu idic(18)(pter ! q22.1::q22.1 ! pter)) in non-mosaic form can be viable, but is associated with severe congenital malformations of the child.
Minor dysmorphism in a child with inherited ring chromosome 18
Medical Research Journal, 2013
The most frequent structural abnormalities of chromosome 18 are deletions and ring chromosome. Clinical features of ring chromosome 18 depend on the extent of the deleted chromosomal segments, the 18p and 18q deletion syndromes. We report on a 6-year-old female child who was presented to the children with special needs clinic, the National Research Center, with a complaint of hyperactivity and occasional episodes of loss of concentration simulating atypical absence seizure. She had a minor nonspecific pattern of dysmorphism and growth retardation; height, head circumference, and body weight measurements were below 2.5 SD. Electroencephalography for the child indicated generalized epileptogenic discharge whereas brain MRI did not indicate any abnormality. Cytogenetic analysis of the patient showed 46,XX, r(18)(65%)/46,XX, double size r(18)(35%); the mother showed the 46,XX, r(18) karyotype in all studied metaphases whereas her father showed the normal male karyotype 46,XY. Fluorescent in-situ hybridization showed that the ring chromosome 18 had deletion of both 18p and 18q subtelomeres. The transmission of ring chromosome 18 from the mother to her daughter with a mosaic karyotype of double-size ring chromosome that resulted only in minor dysmorphism has not been documented in previous studies.
A patient with mosaic partial trisomy 18 resulting from dicentric chromosome breakage
American Journal of Medical Genetics Part A, 2005
We present a patient with minor dysmorphic features and a mosaic karyotype with two different abnormal cell lines, both involving abnormalities of chromosome 18. Twenty percent of cells studied (4/20) had 46 chromosomes with a large derivative pseudoisodicentric chromosome 18. This chromosome was deleted for 18pter and duplicated for part of proximal 18p (18p11.2 based on fluorescence in situ hybridization (FISH) studies and all of 18q. The two copies of portions of chromosome 18 were fused in an inverted fashion (duplicated for 18qter->18p11.3). The smaller der(18) was present in 80% of cells studied (16/20) and had a normal q-arm, while the p-arm was missing the subtelomere region but had duplication of a part of 18p. FISH studies showed that the larger derivative 18 contained the 18q subtelomere at each end, but the 18p subtelomere was absent, consistent with fusion of two regions within 18p resulting in deletion of the subtelomeric regions. The smaller der(18) was also missing the 18p subtelomere (with normal 18q as expected). Further testing with BAC clones mapping within 18p11.2 showed that these sequences were duplicated and inverted in both of the der(18)s. These findings lead us to hypothesize that the smaller der(18) was derived from the larger, dicentric 18 following anaphase bridge formation, with breakage distal to the duplicated segment. © 2005 Wiley-Liss, Inc.
Clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18
American Journal of Medical Genetics, 2001
We report here a child with a ring chromosome 5 (r(5)) associated with facial dysmorphology and multiple congenital abnormalities. Fluorescent in situ hybridization (FISH) using bacterial artificial chromosome (BAC) clones was performed to determine the breakpoints involved in the r(5). The 5p deletion extended from 5p13.2-3 to 5pter and measured 34.61 Mb (range: 33.7e35.52 Mb) while the 5q deletion extended from 5q35.3 to 5qter and measured 2.44 Mb (range: 2.31e2.57 Mb). The patient presented signs such as microcephaly, hypertelorism, micrognathia and epicanthal folds, partially recalling those of a deletion of the short arm of chromosome 5 and the "cri-du-chat" syndrome.
Molecular Cytogenetics, 2010
Background: Several cases have been reported of patients with a ring chromosome 18 replacing one of the normal chromosomes 18. Less common are patients with a supernumerary ring chromosomes 18. High resolution whole genome examination in patients with multiple congenital abnormalities might reveal cytogenetic abnormalities of an unexpected complexity. Results: We report a 24 years old male patient with lower spinal anomalies, hypospadia, bifid scrotum, cryptorchism, anal atresia, kidney stones, urethra anomalies, radial dysplasia, and a hypoplastic thumb. Some of the anomalies overlap with the VACTERL association. Chromosome analysis of cultured peripheral blood lymphocytes revealed an additional ring chromosome in 13% of the metaphases. Both parents had a normal karyotype, demonstrating the de novo origin of this ring chromosome. FISH analysis using whole chromosome paints showed that the additional chromosomal material was derived from chromosome 18. Chromosome analysis of cultured fibroblasts revealed only one cell with the supernumerary ring chromosome in the 400 analyzed. To characterize the ring chromosome in more detail peripheral blood derived DNA was analyzed using SNP-arrays. The array results indicated a 5 Mb gain of the pericentromeric region of chromosome 18q10-q11.2. FISH analysis using BACprobes located in the region indicated the presence of 6 signals on the r(18) chromosome. In addition, microsatellite analysis demonstrated that the unique supernumerary ring chromosome was paternally derived and both normal copies showed biparental disomy. Conclusions: We report on an adult patient with multiple congenital abnormalities who had in 13% of his cells a unique supernumerary ring chromosome 18 that was composed of 6 copies of the 5 Mb gene rich region of 18q11.