Clinical and molecular characterization of the 20q11.2 microdeletion syndrome: Six new patients

Jedraszak, Guillaume; Mathieu‐Dramard, Michèle; Andrieux, Joris; Receveur, Aline; Weber, Astrid; Maye, Una; Foulds, Nicola; Temple, I. Karen; Crolla, John A.; Alex‐Cordier, Marie‐Pierre; Sanlaville, Damien; Ewans, Lisa; Wilson, Meredith; Armstrong, Ruth; Clarkson, Amanda; Copin, Henri; Morin, Gilles

doi:10.1002/ajmg.a.36882

Cited by 6 publications

(21 citation statements)

References 25 publications

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“…Mutations and deletions of SAMHD1 have been associated with systemic lupus erythematosus, and recently homozygous mutations in SAMHD1 were found in 8.3% of Jedraszak et al, 2015Callier et al, 2006Iqbal et al, 2007Hiraki et al, 2011Gervasini et al, 2013Posmyk et al, 2014 Total reported patients Our case (DECIPHER…”

Section: Discussionmentioning

confidence: 75%

“…Recently, a new contiguous gene disorder was described, characterized by a 89 distinct phenotype of intellectual disability, feeding difficulties, craniofacial dysmorphisms, and anomalies of the extremities [Jedraszak et al, 2015]. The SRO in these patients was defined by a 1.6-Mb deletion [Jedraszak et al, 2015] involving several RefSeq sequences, including the 3 OMIM disease-causing genes GDF5 ( * 601146), EPB41L1 ( * 602879), and SAMHD1 ( * 606754).…”

Section: Discussionmentioning

confidence: 99%

“…No cerebral MRI was performed in our patient. In a minority of patients with 20q11.2 deletion encompassing SAMHD1 , cerebral abnormalities were reported, with cortical atrophy being the most common finding at brain MRI (4/12) [Jedraszak et al, 2015;Callier et al, 2006;Iqbal and Al-Owain, 2007;Hiraki et al, 2011]. However, these cerebral abnormalities do not seem to be related to haploinsufficiency of SAMHD1 , according to the role previously attributed to this gene.…”

Section: )mentioning

confidence: 95%

“…To date, 24 unrelated patients have been reported [Fraisse et al, 1981;Petersen et al, 1987;Porfirio et al, 1987;Shabtai et al, 1993;Aldred et al, 2002;Chen et al, 2005;Genevieve et al, 2005;Callier et al, 2006;Borozdin et al, 2007;Iqbal and Al-Owain, 2007;Hiraki et al, 2011;Gervasini et al, 2013;Iourov et al, 2013;Santoro et al, 2013;Posmyk et al, 2014;Jedraszak et al, 2015;Meredith et al, 2017], including 12 with deletions involving the proximal 20q11.2 region [Callier et al, 2006;Iqbal and Al-Owain, 2007;Hiraki et al, 2011;Gervasini et al, 2013;Iourov et al, 2013;Posmyk et al, 2014;Jedraszak et al, 2015;Meredith et al, 2017]. The clinical phenotype shared by these latter patients includes prenatal and postnatal growth retardation, feeding difficulties, psychomotor retardation and intellectual disability of variable degree, craniofacial dysmorphisms (high forehead, frontal bossing, deep-set eyes, midface hypoplasia), and hand/ feet anomalies such as brachydactyly and clinodactyly.…”

mentioning

confidence: 99%

“…Variability of the clinical features seems partly related to the deletion size. A small region of overlap (SRO) extending over 1.6 Mb has been suggested as the minimal critical region [Jedraszak et al, 2015].…”

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confidence: 99%

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First Report of Low-Rate Mosaicism for 20q11.21q12 Deletion and Delineation of the Associated Disorder

Loddo

Alesi²,

Genovese³

et al. 2018

Cytogenet Genome Res

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Interstitial deletions of the long arm of chromosome 20 are very rare, with only 12 reported patients harboring the 20q11.2 microdeletion and presenting a disorder characterized by psychomotor and growth delay, dysmorphisms, and brachy-/clinodactyly. We describe the first case of mosaic 20q11.2 deletion in a 5-year-old girl affected by mild psychomotor delay, feeding difficulties, growth retardation, craniofacial dysmorphisms, and finger anomalies. SNP array analysis disclosed 20% of cells with a 20q11.21q12 deletion, encompassing the 20q11.2 minimal critical region and the 3 OMIM disease-causing genes GDF5, EPB41L1, and SAMHD1. We propose a pathogenic role of other genes mapping outside the small region of overlap, in particular GHRH (growth hormone releasing hormone), whose haploinsufficiency could be responsible for the prenatal onset of growth retardation which is shared by half of these patients. Our patient highlights the utility of chromosomal microarray analysis to identify low-level mosaicism.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: )mentioning

confidence: 95%

mentioning

confidence: 99%

mentioning

confidence: 99%

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First Report of Low-Rate Mosaicism for 20q11.21q12 Deletion and Delineation of the Associated Disorder

Loddo

Alesi²,

Genovese³

et al. 2018

Cytogenet Genome Res

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Chimerism for 20q11.2 microdeletion of GDF5 explains discordant phenotypes in monochorionic‐diamniotic twins

Meredith

Crabb

Vargas

et al. 2017

American J of Med Genetics Pt A

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Microdeletions of 20q11.2 are rare but have been associated with characteristic clinical findings. A 1.6 Mb minimal critical region has been identified that includes three OMIM genes: GDF5, EPB41L1, and SAMHD. Here we describe a male monozygotic, monochorionic-diamniotic twin pair with discordant phenotypes, one with multiple findings that overlap with those reported in 20q11.2 deletions, and the other unaffected. Microarray analysis revealed mosaicism for a 363 Kb deletion encompassing GDF5 in the peripheral blood of both twins, which was confirmed by FISH. Subsequent FISH on buccal cells identified the deletion only in the affected twin. The blood FISH findings were interpreted as representing chimerism resulting from anastomosis and the blood exchange between the twins in utero. The implications of this finding are discussed, as is the contribution of GDF5 to the associated clinical findings of 20q11.2 deletions.

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Clinical and molecular cytogenetic studies of five new patients with 20q11q12 deletion and review of the literature: Proposition of two critical regions

Bensaid,

Bendahmane,

Loddo

et al. 2024

American J of Med Genetics Pt A

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Deletions of the long arm of chromosome 20 (20q) are rare, with only 16 reported patients displaying a proximal interstitial 20q deletion. A 1.62 Mb minimal critical region at 20q11.2, encompassing three genes GDF5, EPB41L1, and SAMHD1, is proposed to be responsible for this syndrome. The leading clinical features include growth retardation, intractable feeding difficulties with gastroesophageal reflux, hypotonia and psychomotor developmental delay. Common facial dysmorphisms including triangular face, hypertelorism, and hypoplastic alae nasi were additionally reported. Here, we present the clinical and molecular findings of five new patients with proximal interstitial 20q deletions. We analyzed the phenotype and molecular data of all previously reported patients with 20q11.2q12 microdeletions, along with our five new cases. Copy number variation analysis of patients in our cohort has enabled us to identify the second critical region in the 20q11.2q12 region and redefine the first region that is initially identified. The first critical region spans 359 kb at 20q11.2, containing six MIM genes, including two disease‐causing genes, GDF5 and CEP250. The second critical region spans 706 kb at 20q12, encompassing four MIM genes, including two disease‐causing genes, MAFB and TOP1. We propose GDF5 to be the primary candidate gene generating the phenotype of patients with 20q11.2 deletions. Moreover, we hypothesize TOP1 as a potential candidate gene for the second critical region at 20q12. Of note, we cannot exclude the possibility of a synergistic role of other genes involved in the deletion, including a contiguous gene deletion syndrome or position effect affecting both critical regions. Further studies focusing on patients with proximal 20q deletions are required to support our hypothesis.

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Clinical and molecular characterization of the 20q11.2 microdeletion syndrome: Six new patients

Cited by 6 publications

References 25 publications

First Report of Low-Rate Mosaicism for 20q11.21q12 Deletion and Delineation of the Associated Disorder

First Report of Low-Rate Mosaicism for 20q11.21q12 Deletion and Delineation of the Associated Disorder

Chimerism for 20q11.2 microdeletion of GDF5 explains discordant phenotypes in monochorionic‐diamniotic twins

Clinical and molecular cytogenetic studies of five new patients with 20q11q12 deletion and review of the literature: Proposition of two critical regions

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