2q Duplication Research Articles

Distal 2q duplication in a patient with intellectual disability

We report on a patient with a distal 16.4-Mb duplication at 2q36.3-qter, who presented with severe intellectual disability, microcephaly, brachycephaly, prominent forehead, hypertelorism, prominent eyes, thin upper lip, and progenia. Copy number analysis using whole exome data detected a distal 2q duplication. This is the first report describing a distal 2q duplication at the molecular level.

A Rare Case of Duplication of Chromosome 2 (q31.3q36.3) in a 4.5-year-old Boy and Review of the Literature

De novo duplication of 2q is very rare. Most cases of 2q duplications result from familial translocations, and are associated with simultaneous monosomy of another chromosome segment. To our knowledge and search in English literature there are less than 20 reported cases of isolated 2q duplication. Hereby we introduce a 4.5-year-old Iranian boy of a non-consanguineous marriage who was referred for cytogenetic study due to developmental delay and intellectual disability. He also had short stature and dysmorphic facial features. He had depressed broad nasal bridge and broad nasal tip, long philtrum and thin upper lip. His hands were edematous and the first phalanxes were broad and the thumbs were larger than normal. The chromosomal analysis revealed isolated 2q31.3q36.3 duplication, and array comparative genomic hybridisation (CGH) confirmed the diagnosis. After six months follow- up, could not walk or speak despite occupational therapy. We also, describe the common morphological characteristics of isolated 2q duplication.

Array Characterization of Prenatally Diagnosed 15q26 Microdeletion and 2q37.1 Duplication: Report of a New Case with Multicystic Kidneys and Review of the Literature.

We report on a molecular cytogenetic characterization of 15q26 deletion and 2q37.1 duplication in a fetus presenting with intrauterine growth restriction (IUGR), diaphragmatic hernia, multicystic kidneys, left kidney pyelectasis, and clubfeet. A terminal 15q26 deletion and a terminal 2q duplication of at least 10 and 9 Mb, respectively, derived from a maternal translocation, were found. The 15q26 deletion represents a contiguous gene deletion syndrome mainly characterized by IUGR, congenital diaphragmatic hernia, and less frequently kidney defects. This deletion encompasses the IGF1R and COUPTF2 genes, known to lead to fetal growth retardation syndrome. However, kidney malformations are less well known in such conditions, and to the best of our knowledge, no candidate gene has been proposed to date. Here, we review the literature of the 15q26 deletion syndrome and suggest that hypoplastic and multicystic kidneys, the most commonly observed anomalies in this condition, should be considered in the prenatal diagnosis setting. Based on COUPTF2 protein function, we hypothesize that its haploinsufficiency might be responsible for the renal pathology.

An Unusual Association: Triple X, 2Q Duplication, and Charge Syndrome

An Unusual Association: Triple X, 2Q Duplication, and Charge Syndrome

P10.04: Clinical outcome of prenatally diagnosed isolated pericardial effusion

Objectives: The aim of this study was to analyze the antenatal characteristics of HLHS, its association with increased nuchal translucency, extracardiac anomalies and other obstetric outcomes. Methods: The medical records of antenatally diagnosed HLHS cases managed at Seoul National University Hospital between January 2007 and April 2012 were reviewed. The main policy of fetuses with HLHS in our institution is to maintain pregnancy and intention to treat with staged surgical palliation. Results: Twenty two fetuses (n = 22) were diagnosed antenatally during this period. Two cases had increased NT (9.09%). Only minor extracardiac anomalies were found in 2 cases (megacisterna magna, unilateral multicystic dysplastic kidney). Most fetuses (90.9%) had an isolated HLHS. Eleven cases performed karyotyping antenatally and all fetuses had normal karyotype. The 4 cases resulted in termination of pregnancy at other hospitals as parents wanted. In 18 cases who maintained pregnancy, there was no intrauterine fetal death and 2 cases (11.1%) developed cardiomegaly at near term. Seventeen cases attempted vaginal delivery, in 3 cases (17.6%), emergent cesarean section occurred due to intrapartum fetal distress. In 14 (82%) cases, labor progressed without any fetal distress. All cases had normal cord ABGA (Cord pH >7.1). Postnatally three cases had diagnosed as Cornelia de lange syndrome, 2q duplication, unilateral MCDK. Conclusions: Most fetuses with HLHS in our institution in Korea were isolated HLHS. And the incidence of increased NT, extracardiac anomalies and abnormal karyotype in HLHS were much less than previous reports in western country. There could be racial difference in characteristics of HLHS fetuses in Asian people.

Molecular characterization of a new patient with a non‐recurrent inv dup del 2q and review of the mechanisms for this rearrangement

We report on newborn baby with microcephaly, facial anomalies, congenital heart defects, hypotonia, wrist contractures, long fingers, adducted thumbs, and club feet. Cytogenetic studies revealed an inverted duplication with terminal deletion (inv dup del) of 2q in the patient and a paternal 2qter deletion polymorphism. Microsatellite markers demonstrated that the inv dup del was maternal in origin and intrachromosomal. Intra or interchromosomal rearrangements may cause this aberration either by a U-type exchange (end-to-end fusion), an unequal crossover between inverted repeats (non-allelic homologous recombination: NAHR), or through breakage-fusion-bridge (BFB) cycles leading to a sister chromatid fusion by non-homologous end joining (NHEJ). A high-resolution oligo array-CGH (244 K) defined the breakpoints and did not detect a single copy region with a size exceeding 12.93 Kb in the fusion site. The size of the duplicated segment was 38.75 Mb, extending from 2q33.1 to 2q37.3 and the size of the terminal deletion was 2.85 Mb in 2q37.3. Our results indicate that the inv dup del (2q) is likely a non-recurrent chromosomal rearrangement generated by a NHEJ mechanism. The major clinical characteristics associated with this 2q rearrangement overlap with those commonly found in patients with 2q duplication reported in the literature.

A new case of 2q duplication supports either a locus for orofacial clefting between markers D2S1897 and D2S2023 or a locus for cleft palate only on chromosome 2q13‐q21

We report on a pure duplication of the proximal chromosome 2q in a 6.5-year-old boy with V-shaped midline cleft palate and bifid uvula, posteriorly located tongue, and micrognathia (Pierre Robin sequence), celiac disease, failure to thrive, and developmental delay. Cytogenetic and FISH analysis indicated a duplication of chromosome 2q13-q22. In general, pure proximal duplication or triplication of 2q is rare. The clinical features and chromosomal breakpoints of the 10 previously reported patients varied, and no common phenotype or proximal duplication/triplication 2q syndrome could be defined to date. However, based on four previous patients with different orofacial clefts and our case, a locus for orofacial clefting may be located at proximal 2q. The duplication/triplication comprised chromosome 2q13 in all five affected individuals including our patient. Our patient and three previous cases (two with cleft palate only (CPO) and one with cleft lip/palate (CL/P)) showed a cytogenetic breakpoint at 2q13, which could support the presence of a critical dominant gene disrupted by a common breakpoint, however, the fifth case with CPO showed different breakpoints, advocating against the disruption of a critical dominant gene and supporting that the overexpression of a gene(s) on chromosome 2q13-q21 may cause cleft palate only (CPO) and Pierre Robin sequence. Hence, our findings support either the presence of one locus for orofacial clefting (CL/P, CPO, and Pierre Robin sequence) between markers D2S1897 (chromosome 2q12.2) and D2S2023 (chromosome 2q14.2), or alternatively the presence of a locus for CPO and Pierre Robin sequence on chromosome 2q13-q21.

Partial trisomy 2q: Report of a patient with dup (2)(q33.1q35)

The partial trisomy 2q phenotype has been well described in the literature, primarily through cases of unbalanced translocations. While these reports contributed to the initial delineation of the phenotype, reports of de novo duplications are valuable in that they exist in the absence of an accompanying monosomy. We describe a 16-month-old female with a de novo duplication of 2q from bands q33.1 to q35. The clinical findings of this patient include a congenital heart defect, dysmorphic facial features, hypotonia, feeding difficulties, and developmental delay. In contrast to most reported individuals with trisomy 2q, this patient demonstrates only mild developmental delays. We compare our findings with other case reports of partial trisomy 2q.

Mild dysmorphic signs in two male sibs with partial trisomy 2q32.1???q35 due to maternal ins(14;2) translocation

We report two male sibs with minor congenital anomalies and moderate to severe developmental delay who are trisomic for the interstitial 2q32.1-->q35 segment. The partial 2q duplication derived from a maternal balanced insertion translocation, 46,XX,dir ins (14;2)(q22;q32.1q35). To the best of our knowledge, no similar case observation has been previously published.

Hepatoblastoma in a Child with Trisomy18: Cytogenetics, Liver Anomalies, and Literature Review

A 26-month-old female with trisomy 18 and repaired omphalocele died of metastatic disease after resection of hepatoblastoma (HB) at 21 months of age. Four other cases (three of them published) suggest that the association of trisomy 18 and HB may be nonrandom. Karyotype abnormalities of the tumor in our case included duplication of 2q and +20, reported previously in HB arising in patients with normal karyotype. Antecedent growth disturbance of liver, either intrinsic (abnormal lobation) or related to contiguous extrinsic anomalies such as omphalocele or local diaphragmatic hypoplasia and possibly augmented by unusual sensitivity to noxious environmental agents, may predispose to hepatoblastoma in trisomy 18. Longevity in trisomy 18 predisposes to both hepatoblastoma and Wilms tumor, possibly by a shared pathway.

Partial trisomy for 2q in a patient with dir dup(2) (q33.1q35).

A 22 year old woman with partial trisomy for the long arm of chromosome 2 is described. The karyotype is 46,XX, dir dup(2)(q33.1q35) de novo confirmed by FISH using a chromosome 2 specific paint. Parental chromosome studies were normal. To our knowledge this is the first report of trisomy for this specific segment of 2q and only the sixth case of de novo direct duplication of 2q, one of which was mosaic. Clinical features include epicanthus, clinodactyly, scoliosis, broad, flat nasal bridge, thin upper lip, long philtrum, and short neck.

Acrofacial dysostosis with ambiguous genitalia

We report on a 46,XY infant with mandibulofacial dysostosis, preaxial and postaxial limb anomalies, urethral stenosis with left hydronephrosis, and ambiguous genitalia with phallic/scrotal transposition. This infant with atypical pre/postaxial acrofacial dysostosis (AFD) is the first to be reported with ambiguous genitalia. The acrofacial dysostoses are a heterogenous group of disorders characterized by varying degrees of mandibulofacial dysostosis with acral limb defects and may represent a polytopic field defect. These disorders have generally been separated on the basis of their limb anomalies into preaxial, postaxial, lethal, and atypical types. Most cases are sporadic, but various causes have been postulated including autosomal dominant and recessive inheritance, a chromosome 2q duplication, and a possible case of diabetic embryopathy. We review the nonfacial/limb anomalies in other cases of AFD and compare them to those of our case, thereby expanding the spectrum of anomalies in these disorders.

De novo direct tandem duplication of the proximal long arm of chromosome 2: 46,XX,dir dup(2)(q11 X 2q14 X 2).

A child is described with a de novo direct duplication of the region 2q11 X 2 leads to 2q14 X 2. She probably represents the first reported case of proximal...