Duplication Of 16q Research Articles

A very rare partial trisomy syndrome: De novo duplication of 16q12.1q23.3 in a Turkish girl with developmental delay and facial dysmorphic features

Trisomy 16 is the most common type of autosomal trisomy associated with spontaneous abortion and is incompatible with life. Upon examining previously reported cases of partial chromosome 16q duplication, it was noted that the majority of cases had complex chromosomal abnormalities due to parental balanced chromosomal translocation carriage. The clinical presentation of very rare pure partial trisomy 16q cases was associated with congenital anomalies, facial dysmorphic findings and intellectual disability. In this study, we evaluated the physical characteristics and genetic data of an 8-month-old girl with developmental delay and facial dysmorphic features. Dysmorphic features including prominent metopic suture, synophrys, asymmetric head shape, triangular and asymmetric face, telecanthus, epicanthal folds, down-slanting palpebral fissures, microphthalmia of the left eye, anteverted nares, smooth and tented philtrum, microretrognathia, low-set posteriorly rotated ears, auricular pits, high-arched palate, thin upper lip and hypotonia were recorded. Her karyotype was 46,XX,add(16)(q24). To identify the extension of the duplicated section, array comparative genomic hybridization (aCGH) analysis was performed, which showed a de novo 29.8 Mb duplication [arr[hgl9] 16q12.1q23.3(52459169-82285105) x 3], interpreted to be pathogenic. We present this case report to clarify the clinical findings of a rare chromosomal anomaly, discuss the genes that may be related to the phenotype and advance the literature in terms of knowledge regarding genotypephenotype correlation.

Molecular cytogenetic characterization of partial monosomy 2p and trisomy 16q in a newborn: A case report.

Trisomy 16q is a rare disorder with severe abnormalities, which always leads to early postnatal mortality. It usually results from a parental translocation, exhibiting 16q duplication associated with another chromosomal deletion. The present study reports on the clinical presentation and molecular cytogenetic results of a small-for-gestational-age infant, consisting of partial trisomy 16q21→qter and monosomy 2p25.3→pter. The proband presented with moderately low birthweight, small anterior fontanelles, prominent forehead, low hairline, telecanthus, flat nasal bridge, choanal atresia, clinodactyly of the fifth fingers, urogenital anomalies, congenital muscular torticollis and congenital laryngomalacia. The last two traits have not previously been reported in any trisomy 16q and monosomy 2p cases. The proband was trisomic for the 16q21→qter chromosomal region with the karyotype 46,XY,der(2)t(2;16)(p25;q21)pat. The chromosomal anomaly was the result of unbalanced segregation of a paternal balanced translocation, 46,XY,t(2;16)(p25;q21). In this case, molecular cytogenetic analysis had a critical role in delineating the proband's clinical phenotype. Although this patient had a 16q21→qter duplication and a 2p25.3→pter deletion, the latter may have had mild phenotypic effects when associated with trisomy 16q. The literature was also reviewed, focusing on cases with the same breakpoints, localizations and clinical features reported in recent years.

A t(5;16) translocation is the likely driver of a syndrome with ambiguous genitalia, facial dysmorphism, intellectual disability, and speech delay.

Genetic studies grounded on monogenic paradigms have accelerated both gene discovery and molecular diagnosis. At the same time, complex genomic rearrangements are also appreciated as potent drivers of disease pathology. Here, we report two male siblings with a dysmorphic face, ambiguous genitalia, intellectual disability, and speech delay. Through quad-based whole-exome sequencing and concomitant molecular cytogenetic testing, we identified two copy-number variants (CNVs) in both affected individuals likely arising from a balanced translocation: a 13.5-Mb duplication on Chromosome 16 (16q23.1 → 16qter) and a 7.7-Mb deletion on Chromosome 5 (5p15.31 → 5pter), as well as a hemizygous missense variant in CXorf36 (also known as DIA1R). The 5p terminal deletion has been associated previously with speech delay, whereas craniofacial dysmorphia and genital/urinary anomalies have been reported in patients with a terminal duplication of 16q. However, dosage changes in either genomic region alone could not account for the overall clinical presentation in our family; functional testing of CXorf36 in zebrafish did not induce defects in neurogenesis or the craniofacial skeleton. Notably, literature and database analysis revealed a similar dosage disruption in two siblings with extensive phenotypic overlap with our patients. Taken together, our data suggest that dosage perturbation of genes within the two chromosomal regions likely drives the syndromic manifestations of our patients and highlight how multiple genetic lesions can contribute to complex clinical pathologies.

Effects of subtelomeric copy number variations in miscarriages

Purpose: This study was performed on miscarriage samples for chromosome analysis to detect copy number variations (CNVs) related to subtelomeric regions, and with these results we aimed to adapt multiplex ligation-dependent probe amplification (MLPA) method for prenatal diagnosis.Materials and methods: The cell cultures and DNA isolations were performed on 60 miscarriage samples. For maternal contamination analysis, DNA isolations and quantitative fluorescent polymerase chain reactions were done using peripheric blood of mothers who had miscarriages. We compared short tandem repeat peak profiles of miscarriage samples and mothers. The subtelomeric regions of the chromosomes were assessed using the MLPA method.Results: Of 43 miscarriage samples, 19 had normal karyotype (44.2%), 10 had numerical abnormalities (23.3%), and 2 had structural abnormalities (4.7%). Subtelomeric 16q duplication was determined in 2 of the 30 miscarriage samples investigated with MLPA method (6.6%).Conclusion: There is no statistically significant difference between two groups (p > 0.05). However, the fact that the 6.6% subtelomeric CNV found in miscarriage samples was not found in controls, showed that further studies are required. We recommend that the miscarriage samples of the couples with recurrent miscarriage should be analyzed in terms of subtelomeric CNV after the exclusion of other clinical reasons.

Clinical, cytogenetic and molecular-cytogenetic characterization of a patient with a de novo tandem proximal-intermediate duplication of 16q and review of the literature

Partial trisomy 16 is rare and most of the reported cases are secondary to chromosome rearrangements resulting in concurrent monosomies or trisomies of a second chromosome. Only a few patients survive the neonatal period and the duplication of the long arm seems to be mainly responsible for the prenatal lethality of the full trisomy 16. The reported patients with a partial 16q trisomy have a wide spectrum of congenital anomalies that include dysmorphic features, central nervous system malformations, failure to thrive, and club feet. The patients with duplications of proximal 16q frequently have short stature, developmental delay, speech delay, learning difficulties, and mild to severe behavioral problems. Here we describe a patient with an inverted de novo tandem duplication of 16q with breakpoints evaluated in detail by molecular-cytogenetic techniques. Main clinical features include postural, motor and speech delay with severe learning difficulties and behavioral problems, obesity, microcephaly, and mild dysmorphic features. In the report we attempt to classify the few reported patients with pure partial duplications of 16q in more narrow and homogeneous groups: proximal, proximal-intermediate, intermediate, and intermediate-distal duplications. Moreover, we emphasize the importance of proper cytogenetic investigation and complete molecular cytogenetic refinement in all cases with a suspected chromosomal anomaly.

Recurrent Distal 16q Duplication and Terminal 22q Deletion: Prenatal Diagnosis and Genetic Counseling

Recurrent Distal 16q Duplication and Terminal 22q Deletion: Prenatal Diagnosis and Genetic Counseling

A t(5;16)(p15.32;q23.3) generating 16q23.3 → qter duplication and 5p15.32 → pter deletion in two siblings with mental retardation, dysmorphic features, and speech delay

We report on two siblings (half brothers on the paternal side) with a syndrome consisting of delayed development, cardiac anomalies, chest deformity, hip rotation, metatarsus adductus, genital hypoplasia, dysmorphic face, depressed nasal bridge, mental retardation, and speech delay. All metaphases examined showed a normal karyotype in the patients, their father, and both mothers. High-resolution array CGH examination revealed a 16q (6 Mb) duplication dup(16)(16q23.3 --> 16qter) and a 5p (0.97 Mb) terminal deletion del(5)(p15.32 --> pter) in both affected boys but not their healthy siblings or parents. Interphase fluorescence in situ hybridization (FISH) confirmed both the 16q duplicated region and the 5p terminal deletion. Clinical abnormalities in the patients included thin upper lip, clinodactyly, and foot deformity, which were reported previously with duplications in 16q23.3. Pectus excavatum, hip rotation, metatarsus adductus, umbilical hernia, brachycephaly, and esotropia were not reported previously in chromosome 16q duplications but may be features that occur intermittently. The 5p deleted region has been associated previously only with speech delay, which was present in both patients. These patients display certain phenotypic characteristics not reported previously in 16q duplication and confirm 5p terminal deletion as an important chromosome anomaly for speech delay.

Application of ROMA (representational oligonucleotide microarray analysis) to patients with cytogenetic rearrangements

PurposeTo demonstrate the accuracy and sensitivity of Representational Oligonucleotide Microarray Analysis (ROMA) to describe copy number changes in patients with chromosomal abnormalities. MethodsROMA was performed using BglII digested DNA from two cases with cytogenetically detected deletions and one case with an unbalanced terminal rearrangement detected only by subtelomeric FISH. Hybridization was to an 85,000-probe oligonucleotide microarray, providing an average resolution of 35 kb. FISH was used to confirm some of the ROMA findings. ResultsBy ROMA, a del(13)(q14.3q21.2) was shown to be noncontiguous, with deletions extending from 53.08 to 61.40 Mb and from 72.88 to 74.83 Mb. The 10-Mb deletion contained only six known genes. FISH confirmed the noncontiguous nature of the deletion, as well as a small amplification in 6q that was also found in the patient's mother. A del(4)(q12q21.2) was found by ROMA to be 23 Mb in length, from 58.8 to 81.9 Mb on chromosome 4, in agreement with the cytogenetically assigned breakpoints. ROMA showed that an unbalanced “subtelomeric” rearrangement involved a 6-Mb deletion of 22q and an 8-Mb duplication of 16q. ConclusionsROMA can define cytogenetic aberrations with extraordinary precision. Unexpected findings included the interrupted nature of the deletion in 13q and the large size of the imbalances in the “subtelomeric” rearrangement. Together with the information from the human genome sequence and proteomics, the ability to define rearrangements with “ultra-high” resolution will improve the ability to provide accurate prognosis both prenatally and postnatally to parents of offspring with chromosomal aberrations.

ATR-16 Due to a De Novo Complex Rearrangement of Chromosome 16

We describe a child with ATR-16 [α-thalassemia (thal)/mental retardation], who was referred forgenetic evaluation because of minor anomalies and developmental delay. Cytogenetic analysisdemonstrated a de novo complex rearrangement of chromosome 16. Fluorescence in situ hybridization(FISH) analysis, using chromosome 16 subtelomeric probes, showed that this patient had a deletion ofthe distal short arm of chromosome 16 that contains the α-globin genes and a duplication of 16q.Analysis of the α-globin locus by Southern blot showed a half normal dose of the α-globin gene.Microsatellite marker studies revealed that the duplicated 16q region was maternal in origin.Hematological studies revealed anemia, hypochromia and occasional cells with Hb H inclusion bodies. Ahematological screening for α-thal should be considered in patients with mild developmental delay and asuggestive phenotype of ATR-16 with microcytic hypochromic anemia and normal iron status. The stellatepattern of the iris, a new finding in our patient, may contribute to a better clinical delineation ofboth syndromes, ATR-16 and/or duplication of 16qter.

Newborn with malformations and a combined duplication of 9pter-q22 and 16q22-qter resulting from unbalanced segregation of a complex maternal translocation.

We report a patient with duplication of 9pter-q22 combined with duplication of 16q22-qter. The chromosome anomaly was the result of a 3:1 segregation of a maternal translocation (46,XX,t[9;16;21]). This newborn had intrauterine growth retardation and microcephaly, the characteristic recognizable pattern of trisomy 9p, cerebellar hypoplasia, a porencephalic cyst in the parieto-occipital region, and rocker-bottom feet. We compare the clinical features with another previously described case of duplication of an identical 9p segment combined with distal 16q duplication of a similar, but not identical segment, as well as with cases with duplication of either one of the two segments.

Three cases of 16q duplication.

Three cases of 16q duplication.