Clinical and Molecular Cytogenetic Characterisation of a Newly Recognised Microdeletion Syndrome Involving 2p15-16.1

Overview

Journal J Med Genet

Specialty Genetics

Date 2006 Sep 12

PMID 16963482

Citations 43

Authors

E Rajcan-Separovic

C Harvard

X Liu

B McGillivray

J G Hall

Y Qiao

J Hurlburt

J Hildebrand

E C R Mickelson

J J A Holden

M E S Lewis

Affiliations

Soon will be listed here.

Abstract

Background: During whole genome microarray-based comparative genomic hybridisation (array CGH) screening of subjects with idiopathic intellectual disability, we identified two unrelated individuals with a similar de novo interstitial microdeletion at 2p15-2p16.1. Both individuals share a similar clinical phenotype including moderate to severe intellectual disability, autism/autistic features, microcephaly, structural brain anomalies including cortical dysplasia/pachygyria, renal anomalies (multicystic kidney, hydronephrosis), digital camptodactyly, visual impairment, strabismus, neuromotor deficits, communication and attention impairments, and a distinctive pattern of craniofacial features. Dysmorphic craniofacial features include progressive microcephaly, flat occiput, widened inner canthal distance, small palpebral fissures, ptosis, long and straight eyelashes, broad and high nasal root extending to a widened, prominent nasal tip with elongated, smooth philtrum, rounding of the upper vermillion border and everted lower lips.

Methods: Clinical assessments, and cytogenetic, array CGH and fluorescence in situ hybridisation (FISH) analyses were performed.

Results: The microdeletions discovered in each individual measured 4.5 Mb and 5.7 Mb, spanning the chromosome 2p region from 57.2 to 61.7 Mb and from 56 to 61.7 Mb, respectively. Each deleted clone in this range demonstrated a dosage reduction from two to one copy in each proband except for clone RP11-79K21, which was present in three copies in each proband and in four copies in their respective parents (two per each chromosome 2 homologue).

Discussion: The common constellation of features found in the two affected subjects indicates that they have a newly recognised microdeletion syndrome involving haploinsufficiency of one or more genes deleted within at least a 4.5-Mb segment of the 2p15-16.1 region.

Citing Articles

Rare Case of 2p15 Microdeletion Syndrome with Deletion Covering and Genes Diagnosed in a Child - A Case Report.

Reka G, Wojciechowska K, Lejman M Appl Clin Genet. 2024; 17:117-124.

PMID: 39050773 PMC: 11268518. DOI: 10.2147/TACG.S465575.

The Role of Bcl11 Transcription Factors in Neurodevelopmental Disorders.

Seigfried F, Britsch S Biology (Basel). 2024; 13(2).

PMID: 38392344 PMC: 10886639. DOI: 10.3390/biology13020126.

Trait - driven analysis of the 2p15p16.1 microdeletion syndrome suggests a complex pattern of interactions between candidate genes.

Miceli M, Failla P, Saccuzzo L, Galesi O, Amata S, Romano C Genes Genomics. 2023; 45(4):491-505.

PMID: 36807877 PMC: 10027778. DOI: 10.1007/s13258-023-01369-7.

A Japanese boy with double diagnoses of 2p15p16.1 microdeletion syndrome and RP2-associated retinal disorder.

Yamazawa K, Shimizu K, Ohashi H, Haruna H, Inoue S, Murakami H Hum Genome Var. 2021; 8(1):46.

PMID: 34921139 PMC: 8683409. DOI: 10.1038/s41439-021-00178-2.

A Novel de novo Frameshift Mutation in the Gene in a Patient with Intellectual Disability Syndrome and Epilepsy.

Korenke G, Schulte B, Biskup S, Neidhardt J, Owczarek-Lipska M Mol Syndromol. 2020; 11(3):135-140.

PMID: 32903878 PMC: 7445578. DOI: 10.1159/000508566.

References

Dijkman R, Tensen C, Jordanova E, Knijnenburg J, Hoefnagel J, Mulder A . Array-based comparative genomic hybridization analysis reveals recurrent chromosomal alterations and prognostic parameters in primary cutaneous large B-cell lymphoma. J Clin Oncol. 2005; 24(2):296-305. DOI: 10.1200/JCO.2005.02.0842. View

Flint J, Wilkie A, Buckle V, Winter R, Holland A, McDermid H . The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat Genet. 1995; 9(2):132-40. DOI: 10.1038/ng0295-132. View

Aldred M, Sanford R, Thomas N, Barrow M, Wilson L, Brueton L . Molecular analysis of 20 patients with 2q37.3 monosomy: definition of minimum deletion intervals for key phenotypes. J Med Genet. 2004; 41(6):433-9. PMC: 1735790. DOI: 10.1136/jmg.2003.017202. View

Moser H . Molecular genetics of peroxisomal disorders. Front Biosci. 2000; 5:D298-306. DOI: 10.2741/moser. View

Gohlke B, Haug K, Fukami M, Friedl W, Noeker M, Rappold G . Interstitial deletion in Xp22.3 is associated with X linked ichthyosis, mental retardation, and epilepsy. J Med Genet. 2000; 37(8):600-2. PMC: 1734650. DOI: 10.1136/jmg.37.8.600. View

Lord C, Risi S, Lambrecht L, Cook Jr E, Leventhal B, DiLavore P . The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. 2000; 30(3):205-23. View

de Vries B, White S, Knight S, Regan R, Homfray T, Young I . Clinical studies on submicroscopic subtelomeric rearrangements: a checklist. J Med Genet. 2001; 38(3):145-50. PMC: 1734836. DOI: 10.1136/jmg.38.3.145. View

de Vries B, Knight S, Homfray T, Smithson S, Flint J, Winter R . Submicroscopic subtelomeric 1qter deletions: a recognisable phenotype?. J Med Genet. 2001; 38(3):175-8. PMC: 1734828. DOI: 10.1136/jmg.38.3.175. View

Lord C, Leventhal B, Cook Jr E . Quantifying the phenotype in autism spectrum disorders. Am J Med Genet. 2001; 105(1):36-8. View

10.

Martin-Subero J, Gesk S, Harder L, Sonoki T, Tucker P, Schlegelberger B . Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma. Blood. 2002; 99(4):1474-7. DOI: 10.1182/blood.v99.4.1474. View

11.

Heilstedt H, Ballif B, Howard L, Lewis R, Stal S, Kashork C . Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome. Am J Hum Genet. 2003; 72(5):1200-12. PMC: 1180272. DOI: 10.1086/375179. View

12.

Dyer M . The pathogenetic role of oncogenes deregulated by chromosomal translocation in B-cell malignancies. Int J Hematol. 2003; 77(4):315-20. DOI: 10.1007/BF02982637. View

13.

Flint J, Knight S . The use of telomere probes to investigate submicroscopic rearrangements associated with mental retardation. Curr Opin Genet Dev. 2003; 13(3):310-6. DOI: 10.1016/s0959-437x(03)00049-2. View

14.

Vissers L, de Vries B, Osoegawa K, Janssen I, Feuth T, Choy C . Array-based comparative genomic hybridization for the genomewide detection of submicroscopic chromosomal abnormalities. Am J Hum Genet. 2003; 73(6):1261-70. PMC: 1180392. DOI: 10.1086/379977. View

15.

Lapierre J, Sanlaville D, Kang J, Ozilou C, Le Lorch M, Waill M . [A preliminary study to assess the value of the DNA chips SpectralChip to detect subtle constitutional chromosome imbalances]. Ann Biol Clin (Paris). 2004; 62(2):203-12. View

16.

Shaw-Smith C, Redon R, Rickman L, Rio M, Willatt L, Fiegler H . Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features. J Med Genet. 2004; 41(4):241-8. PMC: 1735726. DOI: 10.1136/jmg.2003.017731. View

17.

Vissers L, van Ravenswaaij C, Admiraal R, Hurst J, de Vries B, Janssen I . Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. 2004; 36(9):955-7. DOI: 10.1038/ng1407. View

18.

Ledbetter D, Riccardi V, Airhart S, STROBEL R, Keenan B, Crawford J . Deletions of chromosome 15 as a cause of the Prader-Willi syndrome. N Engl J Med. 1981; 304(6):325-9. DOI: 10.1056/NEJM198102053040604. View

19.

Schwartz C, Johnson J, Holycross B, Mandeville T, Sears T, Graul E . Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome. Am J Hum Genet. 1988; 43(5):597-604. PMC: 1715525. View

20.

Rajcan-Separovic E, Mahadevan M, Lefebvre C, Ikeda J, Korneluk R, MacKenzie A . FISH detection of chromosome polymorphism and deletions in the spinal muscular atrophy (SMA) region of 5q13. Cytogenet Cell Genet. 1996; 75(4):243-7. DOI: 10.1159/000134493. View