Deletions of the long arm of chromosome 20 (20q) are rare, with only 16 reported patients displaying a proximal interstitial 20q deletion. A 1.62 Mb minimal critical region at 20q11.2, encompassing three genes GDF5, EPB41L1, and SAMHD1, is proposed to be responsible for this syndrome. The leading clinical features include growth retardation, intractable feeding difficulties with gastroesophageal reflux, hypotonia and psychomotor developmental delay. Common facial dysmorphisms including triangular face, hypertelorism, and hypoplastic alae nasi were additionally reported. Here, we present the clinical and molecular findings of five new patients with proximal interstitial 20q deletions. We analyzed the phenotype and molecular data of all previously reported patients with 20q11.2q12 microdeletions, along with our five new cases. Copy number variation analysis of patients in our cohort has enabled us to identify the second critical region in the 20q11.2q12 region and redefine the first region that is initially identified. The first critical region spans 359 kb at 20q11.2, containing six MIM genes, including two disease-causing genes, GDF5 and CEP250. The second critical region spans 706 kb at 20q12, encompassing four MIM genes, including two disease-causing genes, MAFB and TOP1. We propose GDF5 to be the primary candidate gene generating the phenotype of patients with 20q11.2 deletions. Moreover, we hypothesize TOP1 as a potential candidate gene for the second critical region at 20q12. Of note, we cannot exclude the possibility of a synergistic role of other genes involved in the deletion, including a contiguous gene deletion syndrome or position effect affecting both critical regions. Further studies focusing on patients with proximal 20q deletions are required to support our hypothesis.

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OBJECTIVE: We present prenatal diagnosis of mosaic isochromosome 20q [i(20q)] at amniocentesis, and we review the literature.
METHODS: A 36-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY,i(20)(q10)[27]/46,XY[29]. Prenatal ultrasound findings were unremarkable. The parental karyotypes were normal. Repeat amniocentesis was performed at 20 weeks of gestation. During repeat amniocentesis, array comparative genomic hybridization (aCGH), interphase fluorescence in situ hybridization (FISH) and quantitative fluorescent polymerase chain reaction (QF-PCR) assay were performed on uncultured amniocytes, and conventional cytogenetic analysis, interphase FISH and aCGH were performed on cultured amniocytes. In the repeat amniocentesis, the cultured amniocytes revealed a karyotype of 46,XY. Interphase FISH analysis showed the i(20q) signal in 5.2% (5/96) of the uncultured amniocytes compared with 2% in the control, and in 0.98% (1/102) of the cultured amniocytes compared with 2% in the control. aCGH detected no genomic imbalance in both uncultured and cultured amniocytes. QF-PCR analysis excluded uniparental disomy 20. At 38 weeks of gestation, a healthy 2870-g male baby was delivered with no phenotypic abnormality. The postnatal blood karyotype was 46,XY. FISH analysis on urinary cells showed 2.1% (2/95 cells) mosaicism compared with 1.9% (2/105 cells) in the control.
CONCLUSIONS: Mosaic i(20q) at amniocentesis is a benign condition associated with a favorable outcome in most cases and can be a cell culture artifact confined to cultured amniocytes. Molecular cytogenetic analysis using uncultured amniocytes is useful for rapid confirmation. Prenatal diagnosis of very high percentage of mosaicism for i(20q) at amniocentesis should alert the presence of fetal structural abnormalities. Prenatal diagnosis of mosaic i(20q) at amniocentesis should include a detail examination of fetal brain and spine.

Trisomy 20 is a genetic abnormality in which individuals have an extra copy of chromosome 20. Complete trisomy 20 is rare and believed to be incompatible with life. A mosaic form of trisomy 20, in which only some cells or tissues contain the extra chromosome, is a relatively commonly encountered chromosomal abnormality found during prenatal testing, and c. 90% result in a normal phenotype. However, despite the absence of a consistent phenotype, certain findings have been reported across multiple cases of mosaic trisomy 20. These include an array of morphological findings, developmental delays, and learning disabilities. Beyond physical manifestations, a wide range of developmental and learning delays have also been reported. In this work, we provide an overview of the trisomy 20 literature and a case report of a young adult male with mosaic trisomy 20 who committed homicide. His developmental and life history, eventual diagnosis of mosaic trisomy 20, similarities and differences in his condition compared with prior research findings, and potentially new phenotypic findings associated with trisomy 20 that he manifested (childhood visual hallucinations, self-injury, polydactyly) are presented. Additionally, the potential role of this genetic diagnosis in his neuropsychiatric history and its successful application as a mitigating factor at his capital sentencing trial are described. We did not identify other similar cases during our search of major scientific and legal databases. As a backdrop, the use of genetics in criminal trials is on the rise, and courts are increasingly likely to accept behavioral genetics evidence; therefore, it is crucial that the legal system is well acquainted with the opportunities and limitations of these approaches.

20p13 microdeletion syndrome has been reported to be associated with developmental delays, intellectual disability, epilepsy, and unspecific dysmorphic characteristics. However, only a few cases of 20p13 microdeletion have been described, and therefore its typical features and precise pathogenesis remain elusive.
In this article, we report the case of a 9-month-old infant who presented with a large fontanelle, facial dysmorphism, and failure to thrive. Array-comparative genomic hybridization (aCGH) analysis confirmed a 2.01-Mb microdeletion in chromosome band 20p13 that involved SOX12 and NRSN2, both of which are considered paramount causative genes in patients with 20p13 microdeletion. To elucidate the typical features of 20p13 microdeletion, we further reviewed these previously reported cases and found that motor delay (90%) was the most common manifestation, followed by language delay (60%), abnormal digits (60%), mental retardation (50%), large fontanelle (50%), electroencephalography abnormalities (50%), and seizure (40%).
This report highlights the potential of aCGH as a practical and powerful tool with which to detect submicroscopic chromosomal abnormalities in individuals presenting with a wide spectrum of phenotypes, ranging from facial dysmorphism to failure to thrive. Additionally, the literature review casts new light on the clinical features of 20p13 microdeletion.

Ring chromosome 20 syndrome is a rare chromosomal disorder characterized by childhood-onset drug-resistant epilepsy, behavioral problems and variable cognitive impairment. While most cases occur sporadically, parent-to-child transmission of ring 20 mosaicism has only been reported in a few exceptional families. We identified a further family with mother-to-child transmission of ring 20 mosaicism. Detailed characterization of the ring chromosome showed a complete ring with preserved telomere repetitive sequences. SNP genotyping excluded mosaic uniparental disomy and indicated that the chromosome was transmitted without recombination from mother to child. These results corroborate the findings of a previous study and support the hypothesis that inherited mosaicism is due to transmission of an unstable chromosome either prone to ring opening or to ring re-formation.

OBJECTIVE: We present prenatal diagnosis and molecular genetic characterization of a de novo interstitial deletion of chromosome 20p (20p12-p13) and a literature review of prenatal diagnosis of Alagille syndrome (ALGS).
METHODS: A 33-year-old woman underwent amniocentesis at 17 weeks of gestation because of an abnormal result of combined first-trimester screening. Her husband was 35 years old, and there was no family history of congenital malformations. Amniocentesis revealed a karyotype of 46,XY,del(20)(p12p13), and array comparative genomic hybridization analysis on uncultured amniocytes revealed a 3.749-Mb deletion at 20p13-p12.3 and a 1.84-Mb deletion at 20p12.2 encompassing the gene of JAG1. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. The fetus postnatally manifested characteristic facial features of ALGS. Postnatal molecular cytogenetic analysis of fetal tissues confirmed the prenatal diagnosis. Polymorphic DNA marker analysis revealed a paternal origin of the deletion.
CONCLUSIONS: A de novo interstitial 20p deletion can be caused by a paternal effect. Pregnancy with a fetus affected with ALGS may be associated with an abnormal result of combined first-trimester screening and manifest no detectable ultrasound abnormalities.

BACKGROUND: Orofacial cleft (OFC) is one of the most common congenital malformations with a global incidence of approximately 1/700 live births. Clinically, OFCs can be syndromic or non-syndromic.
METHODS: A 5 years old boy admitted for genetic evaluation because of psychomotor delay, failure to thrive, dysmorphic features and cleft palate. Conventional cytogenetic showed a notably short p arm of one chromosome 20. FISH analysis identified the derivative chromosome 20 as a de novo 20p12.3 deletion.
CONCLUSIONS: We present in this paper a Moroccan patient with syndromic cleft palate caused by a de novo 20p12.3 deletion, and we highlight the interest of FISH in the diagnosis confirmation of chromosomal rearrangement. In practice, 20p12.3 deletion should be considered as an etiological diagnosis in the case of syndromic cleft palate.

Giant cell arteritis (GCA) is an immunologically mediated vasculitis of large and medium-sized vessels, typically affecting the cranial arteries and usually occurring in the elderly. GCA of the female genital tract is extremely rare with only 31 cases reported in the English literature. An 83-year-old white female with postmenopausal vaginal bleeding revealed an endometrial polyp on pelvic ultrasonography following which polypectomy and subsequently hysterectomy with bilateral salpingo-oophorectomy was done. Microscopy revealed a well-differentiated endometrioid adenocarcinoma. Interestingly, classic GCA involving numerous small to medium-sized arteries of the cervix, myometrium, bilateral fallopian tubes, and ovaries was also identified. Hematologic evaluation revealed marginal zone lymphoma with an exceptionally rare 20q deletion. Bilateral temporal artery biopsy was done subsequently, which exhibited GCA on microscopy. Corticosteroid was started that improved her polymyalgia rheumatica symptoms. The patient is on follow-up for 3 years and is doing well. To our knowledge, this is the first case of GCA of the female genital tract associated with a lymphoma and the second case of marginal zone lymphoma with the novel 20q deletion.

We describe a 13-year-old boy with developmental delay and proximal muscle weakness who has monosomy 20 mosaicism in blood and skin cells. Because of asymmetric features (difference in foot size, slightly asymmetric intergluteal cleft), we performed extensive cytogenetic studies in peripheral blood and skin. In cultured and uncultured blood lymphocytes, we found 0.9 and 6.5% of cells with monosomy 20, respectively. In addition, 3.3% of uncultured skin fibroblasts and 1.5% of buccal mucosa cells had monosomy 20. This is the fifth patient published with this chromosomal condition. These patients show variable clinical features, ranging from normal to delayed motor and speech development. There is no apparent relation between the percentage of monosomic cells as studied in blood and the severity of the phenotype. This could be due to different degrees of mosaicism in the other tissues and organs, which may vary considerably from patient to patient. The degree of monosomy 20 mosaicism in blood is in most patients below the detection limit of microarray technology. Therefore, this work illustrates the necessity of detailed cytogenetic investigation of multiple cell types in developmentally retarded patients with normal microarray results, especially when there are subtle physical indications of chromosomal mosaicism.