CLINICAL REPORT
De Novo Interstitial Deletion 2q14.1q22.1: Is There a Recognizable Phenotype? Marie T. Greally,1* Eve Robinson,2 Nicholas M. Allen,2 Donough O’Donovan,2 and John A. Crolla3 1
National Centre for Medical Genetics, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland
2
Department of Paediatrics, University Hospital Galway, Galway, Ireland
3
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wilts, United Kingdom
Manuscript Received: 5 November 2013; Manuscript Accepted: 21 August 2014
In this report we describe a male patient with a rare de novo interstitial deletion of chromosome 2q14.1–q22.1. His karyotype was reported as 46,XY,del(2)(q13q21) but subsequent array comparative genomic hybridization (array CGH) analysis redefined the deletion breakpoints as 2q14.1 and 2q22.1. Eight patients have been reported with deletions either within or spanning the region 2q13 or 2q14 to 2q22.1. In five patients the diagnosis was made by karyotype analysis alone and in three reported patients and the proband array CGH analysis was also performed. When the proband was compared with the eight previously reported patients it was apparent that they shared many clinical findings suggesting that patients with a de novo interstitial deletion involving 2q13 or 2q14 to 2q21 or 2q22 may have a recognizable phenotype. There are 14 known diseaseassociated genes in the deleted region of 2q14.1–q22.1 and their possible phenotypic effects on the proband and the eight previously reported patients are discussed. Ó 2014 Wiley Periodicals, Inc.
Key words: deletion 2q14.1–q22.1; array comparative genomic hybridization (array CGH); dysmorphic features; GLI2
How to Cite this Article: Greally MT, Robinson E, Allen NM, O’Donovan D, Crolla JA. 2014. De novo interstitial deletion 2q14.1q22.1: Is there a recognizable phenotype? Am J Med Genet Part A 9999:1–9.
et al., 2001; Peng et al., 2006; Gustavsson et al., 2006; Kevelam et al., 2011]. The combination of cognitive disability, growth retardation, hypotonia, specific craniofacial and limb abnormalities, and cardiac, renal and/or brain malformations in many of the reported individuals suggests that this chromosome deletion may have a recognizable phenotype. The deleted region in the proband contains 14 OMIM Morbid genes so by analyzing the phenotypic effects of these genes an attempt is made to relate genotype to phenotype in the proband and eight other reported patients with a relatively similar 2q deletion.
CLINICAL REPORT INTRODUCTION Interstitial deletions of the long arm (q) of chromosome 2 are rare, particularly those involving the 2q1–q2 region. Reports of 2q deletions include those that have occurred in association with a translocation [German et al., 1968; Wakamatsu et al., 2001; Shankse et al., 2004; Gustavsson et al., 2006; Ballarati et al., 2009; Porfirio et al., 2012], those that have occurred as an apparently de novo event [Fryns et al., 1977; McConnell et al., 1980; Antich et al., 1983; Lucas et al., 1987; Frydman et al., 1989; Palmer et al., 1990; Davis et al., 1991; Woods et al., 1993; Lurie et al., 1994; Mowat et al., 1998; Eggermann et al., 2000; Baker et al., 2001; Peng et al., 2006; Van Bon et al., 2010] and an inherited deletion [Kevelam et al., 2011]. In order to obtain a relatively clear picture of the phenotype of an individual with a deletion of 2q1–q2, only those patients whose deletion was the sole chromosome abnormality were included in this study. The clinical findings in the proband are compared with eight reported patients with a deletion that spans, or is within, the region 2q13 or 2q14 to 2q22.1 [Lucas et al., 1987; Frydman et al., 1989; Davis et al., 1991; Eggermann et al., 2000; Baker
Ó 2014 Wiley Periodicals, Inc.
The proband is a 31/2-year-old Caucasian male, the second son of healthy, non-consanguineous parents, both of whom were 31 years of age at the time of conception. His older brother is healthy. Birth, at 38 weeks of gestation, was by repeat Caesarean section. The pregnancy was complicated by significant vaginal bleeding at 6 weeks of gestation and by pre-eclampsia at 33 weeks of gestation. Birth weight was 3160g (
De Novo Interstitial Deletion 2q14.1q22.1: Is There a Recognizable Phenotype? Marie T. Greally,1* Eve Robinson,2 Nicholas M. Allen,2 Donough O’Donovan,2 and John A. Crolla3 1
National Centre for Medical Genetics, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland
2
Department of Paediatrics, University Hospital Galway, Galway, Ireland
3
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wilts, United Kingdom
Manuscript Received: 5 November 2013; Manuscript Accepted: 21 August 2014
In this report we describe a male patient with a rare de novo interstitial deletion of chromosome 2q14.1–q22.1. His karyotype was reported as 46,XY,del(2)(q13q21) but subsequent array comparative genomic hybridization (array CGH) analysis redefined the deletion breakpoints as 2q14.1 and 2q22.1. Eight patients have been reported with deletions either within or spanning the region 2q13 or 2q14 to 2q22.1. In five patients the diagnosis was made by karyotype analysis alone and in three reported patients and the proband array CGH analysis was also performed. When the proband was compared with the eight previously reported patients it was apparent that they shared many clinical findings suggesting that patients with a de novo interstitial deletion involving 2q13 or 2q14 to 2q21 or 2q22 may have a recognizable phenotype. There are 14 known diseaseassociated genes in the deleted region of 2q14.1–q22.1 and their possible phenotypic effects on the proband and the eight previously reported patients are discussed. Ó 2014 Wiley Periodicals, Inc.
Key words: deletion 2q14.1–q22.1; array comparative genomic hybridization (array CGH); dysmorphic features; GLI2
How to Cite this Article: Greally MT, Robinson E, Allen NM, O’Donovan D, Crolla JA. 2014. De novo interstitial deletion 2q14.1q22.1: Is there a recognizable phenotype? Am J Med Genet Part A 9999:1–9.
et al., 2001; Peng et al., 2006; Gustavsson et al., 2006; Kevelam et al., 2011]. The combination of cognitive disability, growth retardation, hypotonia, specific craniofacial and limb abnormalities, and cardiac, renal and/or brain malformations in many of the reported individuals suggests that this chromosome deletion may have a recognizable phenotype. The deleted region in the proband contains 14 OMIM Morbid genes so by analyzing the phenotypic effects of these genes an attempt is made to relate genotype to phenotype in the proband and eight other reported patients with a relatively similar 2q deletion.
CLINICAL REPORT INTRODUCTION Interstitial deletions of the long arm (q) of chromosome 2 are rare, particularly those involving the 2q1–q2 region. Reports of 2q deletions include those that have occurred in association with a translocation [German et al., 1968; Wakamatsu et al., 2001; Shankse et al., 2004; Gustavsson et al., 2006; Ballarati et al., 2009; Porfirio et al., 2012], those that have occurred as an apparently de novo event [Fryns et al., 1977; McConnell et al., 1980; Antich et al., 1983; Lucas et al., 1987; Frydman et al., 1989; Palmer et al., 1990; Davis et al., 1991; Woods et al., 1993; Lurie et al., 1994; Mowat et al., 1998; Eggermann et al., 2000; Baker et al., 2001; Peng et al., 2006; Van Bon et al., 2010] and an inherited deletion [Kevelam et al., 2011]. In order to obtain a relatively clear picture of the phenotype of an individual with a deletion of 2q1–q2, only those patients whose deletion was the sole chromosome abnormality were included in this study. The clinical findings in the proband are compared with eight reported patients with a deletion that spans, or is within, the region 2q13 or 2q14 to 2q22.1 [Lucas et al., 1987; Frydman et al., 1989; Davis et al., 1991; Eggermann et al., 2000; Baker
Ó 2014 Wiley Periodicals, Inc.
The proband is a 31/2-year-old Caucasian male, the second son of healthy, non-consanguineous parents, both of whom were 31 years of age at the time of conception. His older brother is healthy. Birth, at 38 weeks of gestation, was by repeat Caesarean section. The pregnancy was complicated by significant vaginal bleeding at 6 weeks of gestation and by pre-eclampsia at 33 weeks of gestation. Birth weight was 3160g (
