Assessment of copy number variations in 120 patients with Poland syndrome

C.M. Vaccari, E. Tassano, M. Torre, Stefania Gimelli, M.T. Divizia, M.V. Romanini, S. Bossi, Ilaria Musante, M. Valle, F. Senes, N. Catena, M.F. Bedeschi, A. Baban, M.G. Calevo, A. M. Acquaviva, M. Lerone, R. Ravazzolo, A. Puliti

Research output: Contribution to journalArticle

Abstract

Background: Poland Syndrome (PS) is a rare congenital disorder presenting with agenesis/hypoplasia of the pectoralis major muscle variably associated with thoracic and/or upper limb anomalies. Most cases are sporadic, but familial recurrence, with different inheritance patterns, has been observed. The genetic etiology of PS remains unknown. Karyotyping and array-comparative genomic hybridization (CGH) analyses can identify genomic imbalances that can clarify the genetic etiology of congenital and neurodevelopmental disorders. We previously reported a chromosome 11 deletion in twin girls with pectoralis muscle hypoplasia and skeletal anomalies, and a chromosome six deletion in a patient presenting a complex phenotype that included pectoralis muscle hypoplasia. However, the contribution of genomic imbalances to PS remains largely unknown. Methods: To investigate the prevalence of chromosomal imbalances in PS, standard cytogenetic and array-CGH analyses were performed in 120 PS patients. Results: Following the application of stringent filter criteria, 14 rare copy number variations (CNVs) were identified in 14 PS patients in different regions outside known common copy number variations: seven genomic duplications and seven genomic deletions, enclosing the two previously reported PS associated chromosomal deletions. These CNVs ranged from 0.04 to 4.71 Mb in size. Bioinformatic analysis of array-CGH data indicated gene enrichment in pathways involved in cell-cell adhesion, DNA binding and apoptosis processes. The analysis also provided a number of candidate genes possibly causing the developmental defects observed in PS patients, among others REV3L, a gene coding for an error-prone DNA polymerase previously associated with Möbius Syndrome with variable phenotypes including pectoralis muscle agenesis. Conclusions: A number of rare CNVs were identified in PS patients, and these involve genes that represent candidates for further evaluation. Rare inherited CNVs may contribute to, or represent risk factors of PS in a multifactorial mode of inheritance. © 2016 The Author(s).
Original languageEnglish
JournalBMC Medical Genetics
Volume17
Issue number1
DOIs
Publication statusPublished - 2016

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Assessment of copy number variations in 120 patients with Poland syndrome. / Vaccari, C.M.; Tassano, E.; Torre, M.; Gimelli, Stefania; Divizia, M.T.; Romanini, M.V.; Bossi, S.; Musante, Ilaria; Valle, M.; Senes, F.; Catena, N.; Bedeschi, M.F.; Baban, A.; Calevo, M.G.; Acquaviva, A. M.; Lerone, M.; Ravazzolo, R.; Puliti, A.

In: BMC Medical Genetics, Vol. 17, No. 1, 2016.

Research output: Contribution to journalArticle

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title = "Assessment of copy number variations in 120 patients with Poland syndrome",
abstract = "Background: Poland Syndrome (PS) is a rare congenital disorder presenting with agenesis/hypoplasia of the pectoralis major muscle variably associated with thoracic and/or upper limb anomalies. Most cases are sporadic, but familial recurrence, with different inheritance patterns, has been observed. The genetic etiology of PS remains unknown. Karyotyping and array-comparative genomic hybridization (CGH) analyses can identify genomic imbalances that can clarify the genetic etiology of congenital and neurodevelopmental disorders. We previously reported a chromosome 11 deletion in twin girls with pectoralis muscle hypoplasia and skeletal anomalies, and a chromosome six deletion in a patient presenting a complex phenotype that included pectoralis muscle hypoplasia. However, the contribution of genomic imbalances to PS remains largely unknown. Methods: To investigate the prevalence of chromosomal imbalances in PS, standard cytogenetic and array-CGH analyses were performed in 120 PS patients. Results: Following the application of stringent filter criteria, 14 rare copy number variations (CNVs) were identified in 14 PS patients in different regions outside known common copy number variations: seven genomic duplications and seven genomic deletions, enclosing the two previously reported PS associated chromosomal deletions. These CNVs ranged from 0.04 to 4.71 Mb in size. Bioinformatic analysis of array-CGH data indicated gene enrichment in pathways involved in cell-cell adhesion, DNA binding and apoptosis processes. The analysis also provided a number of candidate genes possibly causing the developmental defects observed in PS patients, among others REV3L, a gene coding for an error-prone DNA polymerase previously associated with M{\"o}bius Syndrome with variable phenotypes including pectoralis muscle agenesis. Conclusions: A number of rare CNVs were identified in PS patients, and these involve genes that represent candidates for further evaluation. Rare inherited CNVs may contribute to, or represent risk factors of PS in a multifactorial mode of inheritance. {\circledC} 2016 The Author(s).",
keywords = "Array comparative genomic hybridization, Chromosome deletion, Chromosome duplication, Congenital abnormalities, DNA copy number variation, Limb anomalies, Musculoskeletal diseases, Pectoralis muscles, Poland syndrome",
author = "C.M. Vaccari and E. Tassano and M. Torre and Stefania Gimelli and M.T. Divizia and M.V. Romanini and S. Bossi and Ilaria Musante and M. Valle and F. Senes and N. Catena and M.F. Bedeschi and A. Baban and M.G. Calevo and Acquaviva, {A. M.} and M. Lerone and R. Ravazzolo and A. Puliti",
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T1 - Assessment of copy number variations in 120 patients with Poland syndrome

AU - Vaccari, C.M.

AU - Tassano, E.

AU - Torre, M.

AU - Gimelli, Stefania

AU - Divizia, M.T.

AU - Romanini, M.V.

AU - Bossi, S.

AU - Musante, Ilaria

AU - Valle, M.

AU - Senes, F.

AU - Catena, N.

AU - Bedeschi, M.F.

AU - Baban, A.

AU - Calevo, M.G.

AU - Acquaviva, A. M.

AU - Lerone, M.

AU - Ravazzolo, R.

AU - Puliti, A.

N1 - Export Date: 28 March 2017

PY - 2016

Y1 - 2016

N2 - Background: Poland Syndrome (PS) is a rare congenital disorder presenting with agenesis/hypoplasia of the pectoralis major muscle variably associated with thoracic and/or upper limb anomalies. Most cases are sporadic, but familial recurrence, with different inheritance patterns, has been observed. The genetic etiology of PS remains unknown. Karyotyping and array-comparative genomic hybridization (CGH) analyses can identify genomic imbalances that can clarify the genetic etiology of congenital and neurodevelopmental disorders. We previously reported a chromosome 11 deletion in twin girls with pectoralis muscle hypoplasia and skeletal anomalies, and a chromosome six deletion in a patient presenting a complex phenotype that included pectoralis muscle hypoplasia. However, the contribution of genomic imbalances to PS remains largely unknown. Methods: To investigate the prevalence of chromosomal imbalances in PS, standard cytogenetic and array-CGH analyses were performed in 120 PS patients. Results: Following the application of stringent filter criteria, 14 rare copy number variations (CNVs) were identified in 14 PS patients in different regions outside known common copy number variations: seven genomic duplications and seven genomic deletions, enclosing the two previously reported PS associated chromosomal deletions. These CNVs ranged from 0.04 to 4.71 Mb in size. Bioinformatic analysis of array-CGH data indicated gene enrichment in pathways involved in cell-cell adhesion, DNA binding and apoptosis processes. The analysis also provided a number of candidate genes possibly causing the developmental defects observed in PS patients, among others REV3L, a gene coding for an error-prone DNA polymerase previously associated with Möbius Syndrome with variable phenotypes including pectoralis muscle agenesis. Conclusions: A number of rare CNVs were identified in PS patients, and these involve genes that represent candidates for further evaluation. Rare inherited CNVs may contribute to, or represent risk factors of PS in a multifactorial mode of inheritance. © 2016 The Author(s).

AB - Background: Poland Syndrome (PS) is a rare congenital disorder presenting with agenesis/hypoplasia of the pectoralis major muscle variably associated with thoracic and/or upper limb anomalies. Most cases are sporadic, but familial recurrence, with different inheritance patterns, has been observed. The genetic etiology of PS remains unknown. Karyotyping and array-comparative genomic hybridization (CGH) analyses can identify genomic imbalances that can clarify the genetic etiology of congenital and neurodevelopmental disorders. We previously reported a chromosome 11 deletion in twin girls with pectoralis muscle hypoplasia and skeletal anomalies, and a chromosome six deletion in a patient presenting a complex phenotype that included pectoralis muscle hypoplasia. However, the contribution of genomic imbalances to PS remains largely unknown. Methods: To investigate the prevalence of chromosomal imbalances in PS, standard cytogenetic and array-CGH analyses were performed in 120 PS patients. Results: Following the application of stringent filter criteria, 14 rare copy number variations (CNVs) were identified in 14 PS patients in different regions outside known common copy number variations: seven genomic duplications and seven genomic deletions, enclosing the two previously reported PS associated chromosomal deletions. These CNVs ranged from 0.04 to 4.71 Mb in size. Bioinformatic analysis of array-CGH data indicated gene enrichment in pathways involved in cell-cell adhesion, DNA binding and apoptosis processes. The analysis also provided a number of candidate genes possibly causing the developmental defects observed in PS patients, among others REV3L, a gene coding for an error-prone DNA polymerase previously associated with Möbius Syndrome with variable phenotypes including pectoralis muscle agenesis. Conclusions: A number of rare CNVs were identified in PS patients, and these involve genes that represent candidates for further evaluation. Rare inherited CNVs may contribute to, or represent risk factors of PS in a multifactorial mode of inheritance. © 2016 The Author(s).

KW - Array comparative genomic hybridization

KW - Chromosome deletion

KW - Chromosome duplication

KW - Congenital abnormalities

KW - DNA copy number variation

KW - Limb anomalies

KW - Musculoskeletal diseases

KW - Pectoralis muscles

KW - Poland syndrome

U2 - 10.1186/s12881-016-0351-x

DO - 10.1186/s12881-016-0351-x

M3 - Article

VL - 17

JO - BMC Medical Genetics

JF - BMC Medical Genetics

SN - 1471-2350

IS - 1

ER -