Delineating the 15q13.3 microdeletion phenotype: A case series and comprehensive review of the literature

Genetics in Medicine

Volumn 17, Issue 2, 2015, Pages 149-157

  Lowther, Chelsea ^a,b   Costain, Gregory ^a   Stavropoulos, Dimitri J ^c,d   Melvin, Rebecca ^a   Silversides, Candice K ^e,f   Andrade, Danielle M ^d,g   So, Joyce ^d,h   Faghfoury, Hanna ^e   Lionel, Anath C ^b,i   Marshall, Christian R ^b,i   Scherer, Stephen W ^b,i   Bassett, Anne S ^a,b,d,e  

^a CENTRE FOR ADDICTION AND MENTAL HEALTH   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c HOSPITAL FOR SICK CHILDREN   (Canada)

^d UNIVERSITY OF TORONTO   (Canada)

^e UNIVERSITY HEALTH NETWORK   (Canada)

^f MOUNT SINAI HOSPITAL   (Canada)

^g TORONTO WESTERN HOSPITAL   (Canada)

^h LAKERIDGE HEALTH CORPORATION   (Canada)

ⁱ HOSPITAL FOR SICK CHILDREN   (Canada)

Author keywords

Assortative mating; CHRNA7; KLF13; Penetrance; TRPM1

Indexed keywords

ADULT; AGED; ATTENTION DEFICIT DISORDER; AUTISM; CHILD; CHROMOSOME DELETION; CHROMOSOME MICRODELETION 15Q13.3; COHORT ANALYSIS; CONGENITAL HEART DISEASE; CONGENITAL MALFORMATION; CONTROLLED STUDY; DEVELOPMENTAL DISORDER; EPILEPSY; FEMALE; HOMOZYGOSITY; HUMAN; INTELLECTUAL IMPAIRMENT; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MOOD DISORDER; PHENOTYPE; PLACENTA PREVIA; PREGNANCY; REVIEW; SCHIZOPHRENIA; SEIZURE; SPEECH DISORDER; CASE REPORT; CHROMOSOME 15; CHROMOSOME BREAKAGE; CHROMOSOME DISORDERS; GENETIC ASSOCIATION STUDY; HOMOZYGOTE; INHERITANCE; INTELLECTUAL DISABILITY; PEDIGREE; PREVALENCE; SEIZURES;

ADULT; AGED; CHROMOSOME BREAKPOINTS; CHROMOSOME DELETION; CHROMOSOME DISORDERS; CHROMOSOMES, HUMAN, PAIR 15; COHORT STUDIES; FEMALE; GENETIC ASSOCIATION STUDIES; HOMOZYGOTE; HUMANS; INHERITANCE PATTERNS; INTELLECTUAL DISABILITY; MALE; MIDDLE AGED; PEDIGREE; PHENOTYPE; PLACENTA PREVIA; PREGNANCY; PREVALENCE; SEIZURES;

EID: 84961382143     PISSN: 10983600     EISSN: 15300366     Source Type: Journal    
DOI: 10.1038/gim.2014.83     Document Type: Review

References (40)

1. Pujana MA, Nadal M, Guitart M, Armengol L, Gratacs M, Estivill X. Human chromosome 15q11-q14 regions of rearrangements contain clusters of LCR15 duplicons. Eur J Hum Genet 2002;10:26-35.
2. Bassett AS. Parental origin, DNA structure, and the schizophrenia spectrum. Am J Psychiatry 2011;168:350-353.
3. Sharp AJ, Mefford HC, Li K, et al. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat Genet 2008;40:322-328.
4. van Bon BW, Mefford HC, Menten B, et al. Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from nonpathogenic to a severe outcome. J Med Genet 2009;46:511-523.
5. Helbig I, Mefford HC, Sharp AJ, et al. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet 2009;41:160-162.
6. Costain G, Lionel AC, Merico D, et al. Pathogenic rare copy number variants in community-based schizophrenia suggest a potential role for clinical microarrays. Hum Mol Genet 2013;22:4485-4501.
7. Miller DT, Shen Y, Weiss LA, et al. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J Med Genet 2009;46:242-248.
8. Dolcetti A, Silversides CK, Marshall CR, et al. 1q21.1 Microduplication expression in adults. Genet Med 2013;15:282-289.
9. Kaminsky EB, Kaul V, Paschall J, et al. An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet Med 2011;13:777-784.
10. Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010;86:749-764.
11. Scott F, Murphy K, Carey L, et al. Prenatal diagnosis using combined quantitative fluorescent polymerase chain reaction and array comparative genomic hybridization analysis as a first-line test: results from over 1000 consecutive cases. Ultrasound Obstet Gynecol 2013;41:500-507.
12. Silversides CK, Lionel AC, Costain G, et al. Rare copy number variations in adults with tetralogy of Fallot implicate novel risk gene pathways. PLoS Genet 2012;8:e1002843.
13. Fung WL, Chow EW, Webb GD, Gatzoulis MA, Bassett AS. Extracardiac features predicting 22q11.2 deletion syndrome in adult congenital heart disease. Int J Cardiol 2008;131:51-58.
14. Bushby KM, Cole T, Matthews JN, Goodship JA. Centiles for adult head circumference. Arch Dis Child 1992;67:1286-1287.
15. Health Canada. Canadian Perinatal Health Report, 2008. Minister of Public Works and Government Services Canada: Ottawa, Canada, 2008.
16. Kramer MS, Platt RW, Wen SW, et al.; Fetal/Infant Health Study Group of the Canadian Perinatal Surveillance System. A new and improved populationbased Canadian reference for birth weight for gestational age. Pediatrics 2001;108:E35.
17. Firth HV, Richards SM, Bevan AP, et al. DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources. Am J Hum Genet 2009;84:524-533.
18. Masurel-Paulet A, Andrieux J, Callier P, et al. Delineation of 15q13.3 microdeletions. Clin Genet 2010;78:149-161.
19. Spielmann M, Reichelt G, Hertzberg , et al. Homozygous deletion of chromosome 15q13.3 including CHRNA7 causes severe mental retardation, seizures, muscular hypotonia, and the loss of KLF13 and TRPM1 potentially cause macrocytosis and congenital retinal dysfunction in siblings Eur J Med Genet 2011;54:e441-e445.
20. Masurel-Paulet A, Drumare I, Holder M, et al. Further delineation of eye manifestations in homozygous 15q13.3 microdeletions including TRPM1: a differential diagnosis of ceroid lipofuscinosis. Am J Med Genet A 2014;164A:1537-1544.
21. Stefansson H, Meyer-Lindenberg A, Steinberg S, et al. CNVs conferring risk of autism or schizophrenia affect cognition in controls. Nature 2014;505:361-366.
22. Mefford HC, Muhle H, Ostertag P, et al. Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. PLoS Genet 2010;6:e1000962.
23. Wapner RJ, Martin CL, Levy B, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 2012;367:2175-2184.
24. Fiorentino F, Napoletano S, Caiazzo F, et al. Chromosomal microarray analysis as a first-line test in pregnancies with a priori low risk for the detection of submicroscopic chromosomal abnormalities. Eur J Hum Genet 2013;21:725-730.
25. Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr 2011;159:332-339 e331.
26. Costain G, McDonald-McGinn DM, Bassett AS. Prenatal genetic testing with chromosomal microarray analysis identifies major risk variants for schizophrenia and other later-onset disorders. Am J Psychiatry 2013;170:1498.
27. Prasun P, Hankerd M, Kristofice M, Scussel L, Sivaswamy L, Ebrahim S. Compound heterozygous microdeletion of chromosome 15q13.3 region in a child with hypotonia, impaired vision, and global developmental delay. Am J Med Genet A 2014;164:1815-1820.
28. Costain G, Chow EW, Silversides CK, Bassett AS. Sex differences in reproductive fitness contribute to preferential maternal transmission of 22q11.2 deletions. J Med Genet 2011;48:819-824.
29. Cresswell JA, Ronsmans C, Calvert C, Filippi V. Prevalence of placenta praevia by world region: a systematic review and meta-analysis. Trop Med Int Health 2013;18:712-724.
30. Rao KP, Belogolovkin V, Yankowitz J, Spinnato JA 2nd. Abnormal placentation: evidence-based diagnosis and management of placenta previa, placenta accreta, and vasa previa. Obstet Gynecol Surv 2012;67:503-519.
31. Hoppman-Chaney N, Wain K, Seger PR, Superneau DW, Hodge JC. Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype. Clin Genet 2013;83:345-351.
32. Liao J, DeWard SJ, Madan-Khetarpal S, Surti U, Hu J. A small homozygous microdeletion of 15q13.3 including the CHRNA7 gene in a girl with a spectrum of severe neurodevelopmental features. Am J Med Genet A 2011;155A:2795-2800.
33. Ionita-Laza I, Xu B, Makarov V, et al. Scan statistic-based analysis of exome sequencing data identifies FAN1 at 15q13.3 as a susceptibility gene for schizophrenia and autism. Proc Natl Acad Sci USA 2014;111: 343-348.
34. Audo I, Kohl S, Leroy BP, et al. TRPM1 is mutated in patients with autosomalrecessive complete congenital stationary night blindness. Am J Hum Genet 2009;85:720-729.
35. Heard ME, Pabona JM, Clayberger C, Krensky AM, Simmen FA, Simmen RC. The reproductive phenotype of mice null for transcription factor Krppel-like factor 13 suggests compensatory function of family member Krppel-like factor 9 in the peri-implantation uterus. Biol Reprod 2012;87:115.
36. Pabona JM, Zeng Z, Simmen FA, Simmen RC. Functional differentiation of uterine stromal cells involves cross-regulation between bone morphogenetic protein 2 and Kruppel-like factor (KLF) family members KLF9 and KLF13. Endocrinology 2010;151:3396-3406.
37. Costain G, Bassett AS. Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era. Appl Clin Genet 2012;5: 1-18.
38. Brzustowicz LM, Bassett AS. miRNA-mediated risk for schizophrenia in 22q11.2 deletion syndrome. Front Genet 2012;3:1-9.
39. Mellios N, Sur M. The emerging role of microRNAs in schizophrenia and autism spectrum disorders. Front Psychiatry 2012;3:1-9.
40. MacDonald JR, Ziman R, Yuen RK, Feuk L, Scherer SW. The Database of Genomic Variants: a curated collection of structural variation in the human genome. Nucleic Acids Res 2014;42(Database issue):D986-D992.