- Email: [email protected]
Molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 8 associated with congenital hypoplasia of the tongue and review of the literature
Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 323e326
Contents lists available at ScienceDirect
Taiwanese Journal of Obstetrics & Gynecology journal homepage: www.tjog-online.com
Case Report
Molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 8 associated with congenital hypoplasia of the tongue and review of the literature Hui-Yuan Shao, Zong-Yu Miao, Xiao-Yan Liu, Xiao-Fei Hou, Hong Wu* Medical Laboratory Center, The Affiliated Yantai Yu Huang Ding Hospital of Qingdao University Medical College, Shandong, China
a r t i c l e i n f o
a b s t r a c t
Article history: Accepted 18 November 2019
Objective: To present molecular cytogenetic characterization of mosaic supernumerary ring chromosome 8 which has trisomy of a region of chromosome 8p12-q21.13 associated with congenital hypoplasia of the tongue and review of the literature. Case report: A 27 year-old woman presented with congenital hypoplasia of the tongue. The chromosome karyotype of peripheral blood lymphocytes was detected by conventional cytogenetic analysis. The genome copy number variations were detected by SNP array. Conventional cytogenetic analysis of the peripheral blood revealed a karyotype of 47,XX,þmar[60]/46,XX[40]. SNP array revealed that there was a duplication of 45.2 Mb at arr[hg19] 8p12q21.13(36,013,636e81,263,140) 2e3. Conclusion: With this study a patient involving mosaic trisomy 8p12-q21.13 along with clinical properties, is described and compared to previously reported cases involving a small supernumerary marker chromosome (sSMC) derived from chromosome 8. © 2020 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Small supernumerary marker chromosome (sSMC) Chromosome 8 SNP array
Introduction
Case presentation
Supernumerary marker chromosome (sSMC), which is equal to or smaller than that of chromosome 20, is a structurally abnormal chromosome [1]. sSMC derived from chromosome 8 is rare. The phenotype of patients with sSMC(8) ranges from almost normal to variable degrees of abnormalities. Common clinical features of the patient included developmental delay [2e7], mental retardation [5,7], intellectual disability [6], severe hypotonia [7,8], hypospadias [7,8], attention deficit hyperactivity disorder(ADHD) [2,6,9], skeletal anomalies [3,10,11], atypical facial appearance [5,7,10], Renal dysplasia [12,13] and so on. Here, we present an additional Case of sSMC(8) derived from r(8) (p12q21.13) with congenital hypoplasia of the tongue.
A 27 year-old, gravida 1, para 1, woman presented with congenital hypoplasia of the tongue, and her little boy who was accompanied by abnormal brain development and hermaphroditism died after born one month. The patient is free from harmful substances and radiation exposure history as well as family history of chromosome disease. For genetic counseling, conventional cytogenetic analysis was performed on the peripheral blood to determine the karyotype and single nucleotide polymorphism array (SNP array) detected by AffymetrixCytoScan 750K Array (Affymetrix, USA) was used to detect the genome copy number variations (CNVs). Conventional cytogenetic analysis of the peripheral blood revealed a karyotype of 47,XX,þmar[60]/46,XX[40] (Fig. 1). SNP array revealed that there was a duplication of 45.2 Mb at arr[hg19] 8p12q21.13(36,013,636e81,263,140) 2e3 in 51% of the patient's cells and the duplicated chromosomal section contains 134 OMIM genes including FGFR1 and CHD7 (Fig. 2).
* Corresponding author. Medical Laboratory Center, The affiliated Yantai Yu Huang Ding Hospital of Qingdao University Medical College, 20#, the East Road of Yu Huang Ding, zhifu district, Yantai, 264000, Shandong, China. E-mail address: [email protected] (H. Wu).
https://doi.org/10.1016/j.tjog.2020.01.025 1028-4559/© 2020 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
324
H.-Y. Shao et al. / Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 323e326
Fig. 1. The chromosome karyotype of the patient. The normal Chromosome8 was marked by black arrow, and the sSMC was marked by red arrow.
Fig. 2. The genome copy number variations were detected by SNP array.
H.-Y. Shao et al. / Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 323e326
325
Table 1 Cases with an sSMC(8) encompassing the 8q12.2 critical region. authors
karyotype
00119445genome copy number variations
abnormal phenotype
Eyüpoǧlu FC et al[20]
most47,XY,þr(?)[47]/46,XY [36]
43.921 Mb gene dosage increase in 8 p 11.21-q21.13
Chih-ping Chen et al[7]
47,XY,þmar[17]/46,XY[23]
33.95 Mb gene dosage increase in 8p 12-q 13.1
Liehr [21]
47,XY,þmin(8)(::p 11.1/q21.? 3::)[5]/46,XY[15]
Liehr [21]
47,XY,þr(8)(::p10/q23.3::)
Anderlid et al[22]
47,XY,þr(8)(::p 10/q21.1::)/ 46,XX
Multiple congenital anomalies, developmental delay, thoracolumbar scoliosis, mild pulmonary stenosis, laryngomalacia, atypical facial appearance developmental delay, mild mental retardation, hypospadias , strabismus, hypotonia, arachnoid cyst developmental delay, hip dysplasia, cardio myopathy, partial right ptosis, congenital stridor short neck, epicanthic folds, low-set dysplastic ears, frontal bossing, broad/flat nasal bridge. psychomotor retardation, craniofacial dysmorphism, megaureter,hypertelorism, ear abnormalities, finger and foot dysmorphism, hydronephrosis, no urethra, clubfoot, myopia,mild hearing loss. delayed motor development, hearing loss, difficulty in social communication, facial dysmorphism, mental retardation
Discussion sSMC, which may result from translocations, is a type of structurally abnormal chromosome. It has been confirmed that 64% of sSMC inherited from parents and 36% of sSMC arised de novo [12]. About 28% of sSMC originated from a nonacrocentric chromosome has phenotypic abnormalities [6]. In this report, the patient accompanied with congenital hypoplasia of the tongue. For genetic counseling, conventional cytogenetic analysis was performed and revealed a karyotype of 47,XX,þmar[60]/ 46,XX[40]. SNP array revealed that there was a duplication of 45.2 Mb at arr[hg19] 8p12q21.13(36,013,636e81,263,140) 2e3 in 51% of the patient's cells. The duplicated chromosomal section contains 134 OMIM genes including FGFR1 and CHD7. Hypoplasia of tongue is congenital birth defects, greatly affecting individuals' quality of life. Studies have shown that FGFR1 signaling increased translation of WNT signaling components [14], and Wnt/Notch/Pax7 genetic hierarchy played a key role for the lingual epithelial signals in supporting the integrity of the lamina propria and muscular tissue during tongue development [15]. So the excessive expression of FGFR1 gene may be one of the causes of hypoplasia of the tongue. However, this inference needs to be further tested. To date about 70 cases of sSMC(8) have been reported, cases with an sSMC(8) encompassing the 8q12.2 critical region are relatively seldom, and all are associated with serious phenotypic
abnormalities, such as developmental delay, hypospadias or no urethra, abnormal skeletal development, mental retardation, epilepsy, dysaudia, facial dysmorphism (Table 1). And studies have shown that FGFR1 mutation was associated with Hartsfield syndrome, Pfeiffer syndrome and Hypogonadotropic hypogonadism 2 with or without anosmia, and CHD7 mutation was associated with CHARGE syndrome [16e19]. These diseases all are associated with serious phenotypic abnormalities, such as Facial deformity, limb deformity, abnormal heart, growth retardation, craniosynostosis, and genital insufficiency and so on. However, the patient in this report presented only with congenital hypoplasia of the tongue. So this report is especially helpful to supplement the phenotypic diversity of patients with an sSMC(8) involving 8q12.2 critical region. In addition, previous reports showed that sSMC(8) involving 8p11.2/q11.21 was relatively common, at least 18 cases with an sSMC(8) encompassing the 8p11.2/q11.21 have been reported. The phenotype of patients ranges from almost normal to variable degrees of abnormalities. Developmental delay,intellectual disability, skeletal anomalies were the main characteristics in cases with sSMC(8) involving 8p11.2/q11.21(Table 2). In summary, we present molecular cytogenetic characterization of mosaicism for an sSMC(8) derived from r(8)(p12q21.13). This report shows that an sSMC(8) derived from r(8)(p12q21.13) could be associated with congenital hypoplasia of the tongue. In addition, for the future pregnancy, prenatal diagnosis technique, such as fetal ultrasound, karyotype analysis and chromosomal microarray analysis should be performed to avoid the birth of the chromosomal child.
Table 2 Cases with an sSMC(8) encompassing the 8p11.2/q11.21. Clinical features
Clinical cases
Reference
almost normal phenotype abnormal phenotype Developmental delay Intellectual disability Skeletal anomalies Autism severe hypotonia microcephaly attention deflicit hyperactivity disorder atypical facial appearance language delay omphalocele obesity multicystic kidney disease mild ventriculomegaly hypospadias
4 14 7 5 4 2 2 2 2 2 1 1 1 1 1 1
[21,23] [2e4,6,9,11,21] [5,6,11,21,24] [3,6,10,11] [21,24] [8,11] [11,21] [2,9,21] [5,10] [3] [21] [6] [12] [12] [8]
Authors’ contributions Hui-Yuan Shao and Zong-Yu Miao wrote the manuscript and coordinated the clinical analysis of the patients, so they contributed equally to this work. Declaration of Competing Interest The authors declare that they have no competing interests. Acknowledgements We thank the patient and her family members for their participation in this study.
326
H.-Y. Shao et al. / Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 323e326
References [1] Liehr T, Claussen U, Starke H. Small supernumerary marker chromosomes (sSMC) in humans. Cyt ogenet Genome Res 2004;107:55e67. [2] Bettio D, Baldwin EL, Carrozzo R, Vignoli A, May L, Venci A, et al. Molecular cytogenetic and clinical findings in a patient with a small supernumerary r(8) mosaicism. Am J Med Genet 2008;146A:247e50. [3] Spinner NB, Grace KR, Owens NL, Sovinsky L, Pellegrino JE, McDonaldMcGinn D, et al. Mosaicism for a chromosome 8-derived minute marker chromosome in a patient with manifestations of trisomy 8 mosaicism. Am J Med Genet 1995;56:22e4. [4] Brecevic L, Michel S, Starke H, Müller K, Kosyakova N, Mrasek K, et al. Multicolor FISH used for the characterization of small supernumerary marker chromosomes (sSMC) in commercially available immortalized cell lines. Cyt ogenet Genome Res 2006;114:319e24. [5] Ripperger T, Tauscher M, Praulich I, Pabst B, Teigler-Schlegel A, Yeoh A, et al. Constitutional trisomy 8p11.21-q11.21 mosaicism: a germline alteration predisposing to myeloid leukaemia. Br J Haematol 2011;155:209e17. [6] Chen CP, Lin SP, Chern SR, Wu PS, Chen YN, Chen SW, et al. Molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 8 or r(8)(::p11.22/q11.21::) in an 18-year-old female with short stature, obesity, attention deficit hyperactivity disorder, and intellectual disability. Taiwan J Obstet Gynecol 2016;55:856e60. [7] Chen CP, Lin SP, Lin YH, Chern SR, Wu PS, Chen YN, et al. Molecular cytogenetic characterization of mosaicism for a small Supernumerary marker chromosome derived from chromosome 8 or r(8)(::p12/q13.1::) associated with phenotypic abnormalities. Taiwan J Obstet Gynecol 2016;55:852e5. [8] Sheth F, Andrieux J, Ewers E, Kosyakova N, Weise A, Sheth H, et al. Characterization of sSMC by FISH and molecular techniques. Eur J Med Genet 2011;54:247e55. [9] Baldwin EL, May LF, Justice AN, Martin CL, Ledbetter DH. Mechanisms and consequences of small supernumerary marker chromosomes: from Barbara McClintock to modern genetic-counseling issues. Am J Hum Genet 2008;82: 398e410. [10] Risheg H, Chung W, Gadi I, Pasion R, Schwartz S, Tepperberg J, et al. Two mosaic ring cases with evidence of structural evolution determined by SNP microarray. ASHG; 2009. abstract only online, http://www.ashg.org/ 2009meeting/abstracts/fulltext/f22018.htm. [11] Lopez Melchor M, Guzman Olmedo A, Molina Zayas M, Mora Guijosa A, Perez Sanchez M. Caracterizacion de marcadores cromosomicos mediante CGHarray. A proposito de un caso. Sevillia: Poster on 8th Congreso Nacinoal del Laboratorio Clinico; 2014. [12] Chen CP, Chen M, Ko TM, Ma GC, Tsai FJ, Tsai MS, et al. Prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21] [22]
[23]
[24]
chromosome derived from chromosome 8. Taiwan J Obstet Gynecol 2010;49: 500e5. Chen CP, Chang SD, Su YN, Chen M, Chern SR, Su JW, et al. Rapid positive confirmation of mosaicism for a small supernumerary marker chromosome as r(8) by interphase fluorescence in situ hybridization, quantitative fluorescent polymerase chain reaction, and array comparative genomic hybridization on uncultured amniocytes in a pregnancy with fetal pyelectasis. Taiwan J Obstet Gynecol 2012;51:405e10. Nguyen TM, Kabotyanski EB, Dou Y, Reineke LC, Zhang P, Zhang XH, et al. FGFR1-Activated translation of WNT pathway components with structured 5' UTRs is vulnerable to inhibition of EIF4A-dependent translation initiation. Cancer Res 2018;78:4229e40. Zhu XJ, Yuan X, Wang M, Fang Y, Liu Y, Zhang X, et al. A Wnt/Notch/Pax7 signaling network supports tissue integrity in tongue development. J Biol Chem 2017;292:9409e19. Prasad R, Brewer C, Burren CP. Hartsfield syndrome associated with a novel heterozygous missense mutation in FGFR1 and incorporating tumoral calcinosis. Am J Med Genet 2016;170:2222e5. Variable expressivity Bessenyei B, Tihanyi M, Hartwig M, Szakszon K, Ol ah E. of pfeiffer syndrome in a family with FGFR1 p.Pro252Arg mutation. Am J Med Genet 2014;164A:3176e9. _ Ulubay A, et al. HypoAkkus¸ G, Kotan LD, Durmaz E, Mengen E, Turan I, gonadotropic hypogonadism due to novel FGFR1 mutations. J Clin Res Pediatr Endocrinol 2017;9:95e100. Hale CL, Niederriter AN, Green GE, Martin DM. Atypical phenotypes associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria. Am J Med Genet 2016;170A:344e54. Eyüpoglu FC, Sünnetçi D, Cine N, Savli H, Okten A, Açikg oz EG, et al. ArrayCGH and clinical findings in a patient with a small supernumerary r(8) mosaicism. Genet Couns 2014;25:305e13. Liehr T. Small supernumerary marker chromosomes: chromosome 8. Available at, http://ssmc-tl.com/chromosome-8.html. [Accessed 23 July 2016]. Anderlid B-M, Sahlen S, Schoumans J, Holmberg E, Ahsgren I, Mortier G, et al. Detailed characterization of 12 supernumerary ring chromosomes using micro-FISH and search for uniparental disomy. Am J Med Genet 2001;99: 223e33. Manvelyan M, Riegel M, Santos M, Fuster C, Pellestor F, Mazauric ML, et al. 32 new cases with small supernumerary marker chromosomes (sSMC) detected in connection with fertility problems e detailed molecular cytogenetic characterization and review of the literature. Int J Mol Med 2008;21:705e14. Blanchet P, Puechberty J, Lefort G, Cunz-Shadfar D, Baeza Velasco C, Pinson L, et al. Familial supernumerary chromosome composed of centromeric and pericentromeric regions of chromosome 8 cosegregating with intellectual disability and psychiatric disorder. Eur J Hum Genet 2014;21:165 (Abstractnr. P05.042).
Contents lists available at ScienceDirect
Taiwanese Journal of Obstetrics & Gynecology journal homepage: www.tjog-online.com
Case Report
Molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 8 associated with congenital hypoplasia of the tongue and review of the literature Hui-Yuan Shao, Zong-Yu Miao, Xiao-Yan Liu, Xiao-Fei Hou, Hong Wu* Medical Laboratory Center, The Affiliated Yantai Yu Huang Ding Hospital of Qingdao University Medical College, Shandong, China
a r t i c l e i n f o
a b s t r a c t
Article history: Accepted 18 November 2019
Objective: To present molecular cytogenetic characterization of mosaic supernumerary ring chromosome 8 which has trisomy of a region of chromosome 8p12-q21.13 associated with congenital hypoplasia of the tongue and review of the literature. Case report: A 27 year-old woman presented with congenital hypoplasia of the tongue. The chromosome karyotype of peripheral blood lymphocytes was detected by conventional cytogenetic analysis. The genome copy number variations were detected by SNP array. Conventional cytogenetic analysis of the peripheral blood revealed a karyotype of 47,XX,þmar[60]/46,XX[40]. SNP array revealed that there was a duplication of 45.2 Mb at arr[hg19] 8p12q21.13(36,013,636e81,263,140) 2e3. Conclusion: With this study a patient involving mosaic trisomy 8p12-q21.13 along with clinical properties, is described and compared to previously reported cases involving a small supernumerary marker chromosome (sSMC) derived from chromosome 8. © 2020 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Small supernumerary marker chromosome (sSMC) Chromosome 8 SNP array
Introduction
Case presentation
Supernumerary marker chromosome (sSMC), which is equal to or smaller than that of chromosome 20, is a structurally abnormal chromosome [1]. sSMC derived from chromosome 8 is rare. The phenotype of patients with sSMC(8) ranges from almost normal to variable degrees of abnormalities. Common clinical features of the patient included developmental delay [2e7], mental retardation [5,7], intellectual disability [6], severe hypotonia [7,8], hypospadias [7,8], attention deficit hyperactivity disorder(ADHD) [2,6,9], skeletal anomalies [3,10,11], atypical facial appearance [5,7,10], Renal dysplasia [12,13] and so on. Here, we present an additional Case of sSMC(8) derived from r(8) (p12q21.13) with congenital hypoplasia of the tongue.
A 27 year-old, gravida 1, para 1, woman presented with congenital hypoplasia of the tongue, and her little boy who was accompanied by abnormal brain development and hermaphroditism died after born one month. The patient is free from harmful substances and radiation exposure history as well as family history of chromosome disease. For genetic counseling, conventional cytogenetic analysis was performed on the peripheral blood to determine the karyotype and single nucleotide polymorphism array (SNP array) detected by AffymetrixCytoScan 750K Array (Affymetrix, USA) was used to detect the genome copy number variations (CNVs). Conventional cytogenetic analysis of the peripheral blood revealed a karyotype of 47,XX,þmar[60]/46,XX[40] (Fig. 1). SNP array revealed that there was a duplication of 45.2 Mb at arr[hg19] 8p12q21.13(36,013,636e81,263,140) 2e3 in 51% of the patient's cells and the duplicated chromosomal section contains 134 OMIM genes including FGFR1 and CHD7 (Fig. 2).
* Corresponding author. Medical Laboratory Center, The affiliated Yantai Yu Huang Ding Hospital of Qingdao University Medical College, 20#, the East Road of Yu Huang Ding, zhifu district, Yantai, 264000, Shandong, China. E-mail address: [email protected] (H. Wu).
https://doi.org/10.1016/j.tjog.2020.01.025 1028-4559/© 2020 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
324
H.-Y. Shao et al. / Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 323e326
Fig. 1. The chromosome karyotype of the patient. The normal Chromosome8 was marked by black arrow, and the sSMC was marked by red arrow.
Fig. 2. The genome copy number variations were detected by SNP array.
H.-Y. Shao et al. / Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 323e326
325
Table 1 Cases with an sSMC(8) encompassing the 8q12.2 critical region. authors
karyotype
00119445genome copy number variations
abnormal phenotype
Eyüpoǧlu FC et al[20]
most47,XY,þr(?)[47]/46,XY [36]
43.921 Mb gene dosage increase in 8 p 11.21-q21.13
Chih-ping Chen et al[7]
47,XY,þmar[17]/46,XY[23]
33.95 Mb gene dosage increase in 8p 12-q 13.1
Liehr [21]
47,XY,þmin(8)(::p 11.1/q21.? 3::)[5]/46,XY[15]
Liehr [21]
47,XY,þr(8)(::p10/q23.3::)
Anderlid et al[22]
47,XY,þr(8)(::p 10/q21.1::)/ 46,XX
Multiple congenital anomalies, developmental delay, thoracolumbar scoliosis, mild pulmonary stenosis, laryngomalacia, atypical facial appearance developmental delay, mild mental retardation, hypospadias , strabismus, hypotonia, arachnoid cyst developmental delay, hip dysplasia, cardio myopathy, partial right ptosis, congenital stridor short neck, epicanthic folds, low-set dysplastic ears, frontal bossing, broad/flat nasal bridge. psychomotor retardation, craniofacial dysmorphism, megaureter,hypertelorism, ear abnormalities, finger and foot dysmorphism, hydronephrosis, no urethra, clubfoot, myopia,mild hearing loss. delayed motor development, hearing loss, difficulty in social communication, facial dysmorphism, mental retardation
Discussion sSMC, which may result from translocations, is a type of structurally abnormal chromosome. It has been confirmed that 64% of sSMC inherited from parents and 36% of sSMC arised de novo [12]. About 28% of sSMC originated from a nonacrocentric chromosome has phenotypic abnormalities [6]. In this report, the patient accompanied with congenital hypoplasia of the tongue. For genetic counseling, conventional cytogenetic analysis was performed and revealed a karyotype of 47,XX,þmar[60]/ 46,XX[40]. SNP array revealed that there was a duplication of 45.2 Mb at arr[hg19] 8p12q21.13(36,013,636e81,263,140) 2e3 in 51% of the patient's cells. The duplicated chromosomal section contains 134 OMIM genes including FGFR1 and CHD7. Hypoplasia of tongue is congenital birth defects, greatly affecting individuals' quality of life. Studies have shown that FGFR1 signaling increased translation of WNT signaling components [14], and Wnt/Notch/Pax7 genetic hierarchy played a key role for the lingual epithelial signals in supporting the integrity of the lamina propria and muscular tissue during tongue development [15]. So the excessive expression of FGFR1 gene may be one of the causes of hypoplasia of the tongue. However, this inference needs to be further tested. To date about 70 cases of sSMC(8) have been reported, cases with an sSMC(8) encompassing the 8q12.2 critical region are relatively seldom, and all are associated with serious phenotypic
abnormalities, such as developmental delay, hypospadias or no urethra, abnormal skeletal development, mental retardation, epilepsy, dysaudia, facial dysmorphism (Table 1). And studies have shown that FGFR1 mutation was associated with Hartsfield syndrome, Pfeiffer syndrome and Hypogonadotropic hypogonadism 2 with or without anosmia, and CHD7 mutation was associated with CHARGE syndrome [16e19]. These diseases all are associated with serious phenotypic abnormalities, such as Facial deformity, limb deformity, abnormal heart, growth retardation, craniosynostosis, and genital insufficiency and so on. However, the patient in this report presented only with congenital hypoplasia of the tongue. So this report is especially helpful to supplement the phenotypic diversity of patients with an sSMC(8) involving 8q12.2 critical region. In addition, previous reports showed that sSMC(8) involving 8p11.2/q11.21 was relatively common, at least 18 cases with an sSMC(8) encompassing the 8p11.2/q11.21 have been reported. The phenotype of patients ranges from almost normal to variable degrees of abnormalities. Developmental delay,intellectual disability, skeletal anomalies were the main characteristics in cases with sSMC(8) involving 8p11.2/q11.21(Table 2). In summary, we present molecular cytogenetic characterization of mosaicism for an sSMC(8) derived from r(8)(p12q21.13). This report shows that an sSMC(8) derived from r(8)(p12q21.13) could be associated with congenital hypoplasia of the tongue. In addition, for the future pregnancy, prenatal diagnosis technique, such as fetal ultrasound, karyotype analysis and chromosomal microarray analysis should be performed to avoid the birth of the chromosomal child.
Table 2 Cases with an sSMC(8) encompassing the 8p11.2/q11.21. Clinical features
Clinical cases
Reference
almost normal phenotype abnormal phenotype Developmental delay Intellectual disability Skeletal anomalies Autism severe hypotonia microcephaly attention deflicit hyperactivity disorder atypical facial appearance language delay omphalocele obesity multicystic kidney disease mild ventriculomegaly hypospadias
4 14 7 5 4 2 2 2 2 2 1 1 1 1 1 1
[21,23] [2e4,6,9,11,21] [5,6,11,21,24] [3,6,10,11] [21,24] [8,11] [11,21] [2,9,21] [5,10] [3] [21] [6] [12] [12] [8]
Authors’ contributions Hui-Yuan Shao and Zong-Yu Miao wrote the manuscript and coordinated the clinical analysis of the patients, so they contributed equally to this work. Declaration of Competing Interest The authors declare that they have no competing interests. Acknowledgements We thank the patient and her family members for their participation in this study.
326
H.-Y. Shao et al. / Taiwanese Journal of Obstetrics & Gynecology 59 (2020) 323e326
References [1] Liehr T, Claussen U, Starke H. Small supernumerary marker chromosomes (sSMC) in humans. Cyt ogenet Genome Res 2004;107:55e67. [2] Bettio D, Baldwin EL, Carrozzo R, Vignoli A, May L, Venci A, et al. Molecular cytogenetic and clinical findings in a patient with a small supernumerary r(8) mosaicism. Am J Med Genet 2008;146A:247e50. [3] Spinner NB, Grace KR, Owens NL, Sovinsky L, Pellegrino JE, McDonaldMcGinn D, et al. Mosaicism for a chromosome 8-derived minute marker chromosome in a patient with manifestations of trisomy 8 mosaicism. Am J Med Genet 1995;56:22e4. [4] Brecevic L, Michel S, Starke H, Müller K, Kosyakova N, Mrasek K, et al. Multicolor FISH used for the characterization of small supernumerary marker chromosomes (sSMC) in commercially available immortalized cell lines. Cyt ogenet Genome Res 2006;114:319e24. [5] Ripperger T, Tauscher M, Praulich I, Pabst B, Teigler-Schlegel A, Yeoh A, et al. Constitutional trisomy 8p11.21-q11.21 mosaicism: a germline alteration predisposing to myeloid leukaemia. Br J Haematol 2011;155:209e17. [6] Chen CP, Lin SP, Chern SR, Wu PS, Chen YN, Chen SW, et al. Molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 8 or r(8)(::p11.22/q11.21::) in an 18-year-old female with short stature, obesity, attention deficit hyperactivity disorder, and intellectual disability. Taiwan J Obstet Gynecol 2016;55:856e60. [7] Chen CP, Lin SP, Lin YH, Chern SR, Wu PS, Chen YN, et al. Molecular cytogenetic characterization of mosaicism for a small Supernumerary marker chromosome derived from chromosome 8 or r(8)(::p12/q13.1::) associated with phenotypic abnormalities. Taiwan J Obstet Gynecol 2016;55:852e5. [8] Sheth F, Andrieux J, Ewers E, Kosyakova N, Weise A, Sheth H, et al. Characterization of sSMC by FISH and molecular techniques. Eur J Med Genet 2011;54:247e55. [9] Baldwin EL, May LF, Justice AN, Martin CL, Ledbetter DH. Mechanisms and consequences of small supernumerary marker chromosomes: from Barbara McClintock to modern genetic-counseling issues. Am J Hum Genet 2008;82: 398e410. [10] Risheg H, Chung W, Gadi I, Pasion R, Schwartz S, Tepperberg J, et al. Two mosaic ring cases with evidence of structural evolution determined by SNP microarray. ASHG; 2009. abstract only online, http://www.ashg.org/ 2009meeting/abstracts/fulltext/f22018.htm. [11] Lopez Melchor M, Guzman Olmedo A, Molina Zayas M, Mora Guijosa A, Perez Sanchez M. Caracterizacion de marcadores cromosomicos mediante CGHarray. A proposito de un caso. Sevillia: Poster on 8th Congreso Nacinoal del Laboratorio Clinico; 2014. [12] Chen CP, Chen M, Ko TM, Ma GC, Tsai FJ, Tsai MS, et al. Prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21] [22]
[23]
[24]
chromosome derived from chromosome 8. Taiwan J Obstet Gynecol 2010;49: 500e5. Chen CP, Chang SD, Su YN, Chen M, Chern SR, Su JW, et al. Rapid positive confirmation of mosaicism for a small supernumerary marker chromosome as r(8) by interphase fluorescence in situ hybridization, quantitative fluorescent polymerase chain reaction, and array comparative genomic hybridization on uncultured amniocytes in a pregnancy with fetal pyelectasis. Taiwan J Obstet Gynecol 2012;51:405e10. Nguyen TM, Kabotyanski EB, Dou Y, Reineke LC, Zhang P, Zhang XH, et al. FGFR1-Activated translation of WNT pathway components with structured 5' UTRs is vulnerable to inhibition of EIF4A-dependent translation initiation. Cancer Res 2018;78:4229e40. Zhu XJ, Yuan X, Wang M, Fang Y, Liu Y, Zhang X, et al. A Wnt/Notch/Pax7 signaling network supports tissue integrity in tongue development. J Biol Chem 2017;292:9409e19. Prasad R, Brewer C, Burren CP. Hartsfield syndrome associated with a novel heterozygous missense mutation in FGFR1 and incorporating tumoral calcinosis. Am J Med Genet 2016;170:2222e5. Variable expressivity Bessenyei B, Tihanyi M, Hartwig M, Szakszon K, Ol ah E. of pfeiffer syndrome in a family with FGFR1 p.Pro252Arg mutation. Am J Med Genet 2014;164A:3176e9. _ Ulubay A, et al. HypoAkkus¸ G, Kotan LD, Durmaz E, Mengen E, Turan I, gonadotropic hypogonadism due to novel FGFR1 mutations. J Clin Res Pediatr Endocrinol 2017;9:95e100. Hale CL, Niederriter AN, Green GE, Martin DM. Atypical phenotypes associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria. Am J Med Genet 2016;170A:344e54. Eyüpoglu FC, Sünnetçi D, Cine N, Savli H, Okten A, Açikg oz EG, et al. ArrayCGH and clinical findings in a patient with a small supernumerary r(8) mosaicism. Genet Couns 2014;25:305e13. Liehr T. Small supernumerary marker chromosomes: chromosome 8. Available at, http://ssmc-tl.com/chromosome-8.html. [Accessed 23 July 2016]. Anderlid B-M, Sahlen S, Schoumans J, Holmberg E, Ahsgren I, Mortier G, et al. Detailed characterization of 12 supernumerary ring chromosomes using micro-FISH and search for uniparental disomy. Am J Med Genet 2001;99: 223e33. Manvelyan M, Riegel M, Santos M, Fuster C, Pellestor F, Mazauric ML, et al. 32 new cases with small supernumerary marker chromosomes (sSMC) detected in connection with fertility problems e detailed molecular cytogenetic characterization and review of the literature. Int J Mol Med 2008;21:705e14. Blanchet P, Puechberty J, Lefort G, Cunz-Shadfar D, Baeza Velasco C, Pinson L, et al. Familial supernumerary chromosome composed of centromeric and pericentromeric regions of chromosome 8 cosegregating with intellectual disability and psychiatric disorder. Eur J Hum Genet 2014;21:165 (Abstractnr. P05.042).