Abstract
Phelan-McDermid syndrome (22q13.3 deletion syndrome) is a contiguous gene disorder resulting from the deletion of the distal long arm of chromosome 22. SHANK3, a gene within the minimal critical region, is a candidate gene for the major neurological features of this syndrome. We report clinical and molecular data from a study of nine patients with overlapping interstitial deletions in 22q13 not involving SHANK3. All of these deletions overlap with the largest, but not with the smallest deletion associated with Phelan-McDermid syndrome. The deletion sizes and breakpoints varied considerably among our patients, with the largest deletion spanning 6.9Mb and the smallest deletion spanning 2.7Mb. Eight out of nine patients had a de novo deletion, while in one patient the origin of deletion was unknown. These patients shared clinical features common to Phelan-McDermid syndrome: developmental delay (11/12), speech delay (11/12), hypotonia (9/12), and feeding difficulties (7/12). Moreover, the majority of patients (8/12) exhibited macrocephaly. In the minimal deleted region, we identified two candidate genes, SULT4A1 and PARVB (associated with the PTEN pathway), which could be associated in our cohort with neurological features and macrocephaly/hypotonia, respectively. This study suggests that the haploinsufficiency of genes in the 22q13 region beside SHANK3 contributes to cognitive and speech development, and that these genes are involved in the phenotype associated with the larger Phelan-McDermid syndrome 22q13 deletions. Moreover, because the deletions in our patients do not involve the SHANK3 gene, we posit the existence of a new contiguous gene syndrome proximal to the smallest terminal deletions in the 22q13 region.
| Original language | English |
|---|---|
| Pages (from-to) | 1666-1676 |
| Number of pages | 11 |
| Journal | American Journal of Medical Genetics, Part A |
| Volume | 164 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- 22q13.3 deletion
- PARVB
- Phelan-McDermid syndrome
- SHANK3
- SULT4A1
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
- Medicine(all)
Cite this
Interstitial 22q13 deletions not involving SHANK3 gene : A new contiguous gene syndrome. / Disciglio, Vittoria; Rizzo, Caterina Lo; Mencarelli, Maria Antonietta; Mucciolo, Mafalda; Marozza, Annabella; Di Marco, Chiara; Massarelli, Antonio; Canocchi, Valentina; Baldassarri, Margherita; Ndoni, Enea; Frullanti, Elisa; Amabile, Sonia; Anderlid, Britt Marie; Metcalfe, Kay; Le Caignec, Cédric; David, Albert; Fryer, Alan; Boute, Odile; Joris, Andrieux; Greco, Donatella; Pecile, Vanna; Battini, Roberta; Novelli, Antonio; Fichera, Marco; Romano, Corrado; Mari, Francesca; Renieri, Alessandra.
In: American Journal of Medical Genetics, Part A, Vol. 164, No. 7, 2014, p. 1666-1676.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interstitial 22q13 deletions not involving SHANK3 gene
T2 - A new contiguous gene syndrome
AU - Disciglio, Vittoria
AU - Rizzo, Caterina Lo
AU - Mencarelli, Maria Antonietta
AU - Mucciolo, Mafalda
AU - Marozza, Annabella
AU - Di Marco, Chiara
AU - Massarelli, Antonio
AU - Canocchi, Valentina
AU - Baldassarri, Margherita
AU - Ndoni, Enea
AU - Frullanti, Elisa
AU - Amabile, Sonia
AU - Anderlid, Britt Marie
AU - Metcalfe, Kay
AU - Le Caignec, Cédric
AU - David, Albert
AU - Fryer, Alan
AU - Boute, Odile
AU - Joris, Andrieux
AU - Greco, Donatella
AU - Pecile, Vanna
AU - Battini, Roberta
AU - Novelli, Antonio
AU - Fichera, Marco
AU - Romano, Corrado
AU - Mari, Francesca
AU - Renieri, Alessandra
PY - 2014
Y1 - 2014
N2 - Phelan-McDermid syndrome (22q13.3 deletion syndrome) is a contiguous gene disorder resulting from the deletion of the distal long arm of chromosome 22. SHANK3, a gene within the minimal critical region, is a candidate gene for the major neurological features of this syndrome. We report clinical and molecular data from a study of nine patients with overlapping interstitial deletions in 22q13 not involving SHANK3. All of these deletions overlap with the largest, but not with the smallest deletion associated with Phelan-McDermid syndrome. The deletion sizes and breakpoints varied considerably among our patients, with the largest deletion spanning 6.9Mb and the smallest deletion spanning 2.7Mb. Eight out of nine patients had a de novo deletion, while in one patient the origin of deletion was unknown. These patients shared clinical features common to Phelan-McDermid syndrome: developmental delay (11/12), speech delay (11/12), hypotonia (9/12), and feeding difficulties (7/12). Moreover, the majority of patients (8/12) exhibited macrocephaly. In the minimal deleted region, we identified two candidate genes, SULT4A1 and PARVB (associated with the PTEN pathway), which could be associated in our cohort with neurological features and macrocephaly/hypotonia, respectively. This study suggests that the haploinsufficiency of genes in the 22q13 region beside SHANK3 contributes to cognitive and speech development, and that these genes are involved in the phenotype associated with the larger Phelan-McDermid syndrome 22q13 deletions. Moreover, because the deletions in our patients do not involve the SHANK3 gene, we posit the existence of a new contiguous gene syndrome proximal to the smallest terminal deletions in the 22q13 region.
AB - Phelan-McDermid syndrome (22q13.3 deletion syndrome) is a contiguous gene disorder resulting from the deletion of the distal long arm of chromosome 22. SHANK3, a gene within the minimal critical region, is a candidate gene for the major neurological features of this syndrome. We report clinical and molecular data from a study of nine patients with overlapping interstitial deletions in 22q13 not involving SHANK3. All of these deletions overlap with the largest, but not with the smallest deletion associated with Phelan-McDermid syndrome. The deletion sizes and breakpoints varied considerably among our patients, with the largest deletion spanning 6.9Mb and the smallest deletion spanning 2.7Mb. Eight out of nine patients had a de novo deletion, while in one patient the origin of deletion was unknown. These patients shared clinical features common to Phelan-McDermid syndrome: developmental delay (11/12), speech delay (11/12), hypotonia (9/12), and feeding difficulties (7/12). Moreover, the majority of patients (8/12) exhibited macrocephaly. In the minimal deleted region, we identified two candidate genes, SULT4A1 and PARVB (associated with the PTEN pathway), which could be associated in our cohort with neurological features and macrocephaly/hypotonia, respectively. This study suggests that the haploinsufficiency of genes in the 22q13 region beside SHANK3 contributes to cognitive and speech development, and that these genes are involved in the phenotype associated with the larger Phelan-McDermid syndrome 22q13 deletions. Moreover, because the deletions in our patients do not involve the SHANK3 gene, we posit the existence of a new contiguous gene syndrome proximal to the smallest terminal deletions in the 22q13 region.
KW - 22q13.3 deletion
KW - PARVB
KW - Phelan-McDermid syndrome
KW - SHANK3
KW - SULT4A1
UR - http://www.scopus.com/inward/record.url?scp=84902546649&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84902546649&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.36513
DO - 10.1002/ajmg.a.36513
M3 - Article
VL - 164
SP - 1666
EP - 1676
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 7
ER -