Abstract
Background: Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histone methyl transferase MLL2 gene have been identified as its underlying cause. Methods. Genomic DNAs were extracted from 62 index patients clinically diagnosed as affected by Kabuki syndrome. Sanger sequencing was performed to analyze the whole coding region of the MLL2 gene including intron-exon junctions. The putative causal and possible functional effect of each nucleotide variant identified was estimated by in silico prediction tools. Results: We identified 45 patients with MLL2 nucleotide variants. 38 out of the 42 variants were never described before. Consistently with previous reports, the majority are nonsense or frameshift mutations predicted to generate a truncated polypeptide. We also identified 3 indel, 7 missense and 3 splice site. Conclusions: This study emphasizes the relevance of mutational screening of the MLL2 gene among patients diagnosed with Kabuki syndrome. The identification of a large spectrum of MLL2 mutations possibly offers the opportunity to improve the actual knowledge on the clinical basis of this multiple congenital anomalies/mental retardation syndrome, design functional studies to understand the molecular mechanisms underlying this disease, establish genotype-phenotype correlations and improve clinical management.
| Original language | English |
|---|---|
| Article number | 38 |
| Journal | Orphanet Journal of Rare Diseases |
| Volume | 6 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2011 |
Fingerprint
ASJC Scopus subject areas
- Medicine(all)
- Genetics(clinical)
- Pharmacology (medical)
Cite this
Mutation spectrum of MLL2 in a cohort of kabuki syndrome patients. / Micale, Lucia; Augello, Bartolomeo; Fusco, Carmela; Selicorni, Angelo; Loviglio, Maria N.; Silengo, Margherita Cirillo; Reymond, Alexandre; Gumiero, Barbara; Zucchetti, Federica; D'Addetta, Ester V.; Belligni, Elga; Calcagn, Alessia; Digilio, Maria C.; Dallapiccola, Bruno; Faravelli, Francesca; Forzano, Francesca; Accadia, Maria; Bonfante, Aldo; Clementi, Maurizio; Daolio, Cecilia; Douzgou, Sofia; Ferrari, Paola; Fischetto, Rita; Garavelli, Livia; Lapi, Elisabetta; Mattina, Teresa; Melis, Daniela; Patricelli, Maria G.; Priolo, Manuela; Prontera, Paolo; Renieri, Alessandra; Mencarelli, Maria A.; Scarano, Gioacchino; Monica, Matteo Della; Toschi, Benedetta; Turolla, Licia; Vancini, Alessandra; Zatterale, Adriana; Gabrielli, Orazio; Zelante, Leopoldo; Merla, Giuseppe.
In: Orphanet Journal of Rare Diseases, Vol. 6, No. 1, 38, 2011.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mutation spectrum of MLL2 in a cohort of kabuki syndrome patients
AU - Micale, Lucia
AU - Augello, Bartolomeo
AU - Fusco, Carmela
AU - Selicorni, Angelo
AU - Loviglio, Maria N.
AU - Silengo, Margherita Cirillo
AU - Reymond, Alexandre
AU - Gumiero, Barbara
AU - Zucchetti, Federica
AU - D'Addetta, Ester V.
AU - Belligni, Elga
AU - Calcagn, Alessia
AU - Digilio, Maria C.
AU - Dallapiccola, Bruno
AU - Faravelli, Francesca
AU - Forzano, Francesca
AU - Accadia, Maria
AU - Bonfante, Aldo
AU - Clementi, Maurizio
AU - Daolio, Cecilia
AU - Douzgou, Sofia
AU - Ferrari, Paola
AU - Fischetto, Rita
AU - Garavelli, Livia
AU - Lapi, Elisabetta
AU - Mattina, Teresa
AU - Melis, Daniela
AU - Patricelli, Maria G.
AU - Priolo, Manuela
AU - Prontera, Paolo
AU - Renieri, Alessandra
AU - Mencarelli, Maria A.
AU - Scarano, Gioacchino
AU - Monica, Matteo Della
AU - Toschi, Benedetta
AU - Turolla, Licia
AU - Vancini, Alessandra
AU - Zatterale, Adriana
AU - Gabrielli, Orazio
AU - Zelante, Leopoldo
AU - Merla, Giuseppe
PY - 2011
Y1 - 2011
N2 - Background: Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histone methyl transferase MLL2 gene have been identified as its underlying cause. Methods. Genomic DNAs were extracted from 62 index patients clinically diagnosed as affected by Kabuki syndrome. Sanger sequencing was performed to analyze the whole coding region of the MLL2 gene including intron-exon junctions. The putative causal and possible functional effect of each nucleotide variant identified was estimated by in silico prediction tools. Results: We identified 45 patients with MLL2 nucleotide variants. 38 out of the 42 variants were never described before. Consistently with previous reports, the majority are nonsense or frameshift mutations predicted to generate a truncated polypeptide. We also identified 3 indel, 7 missense and 3 splice site. Conclusions: This study emphasizes the relevance of mutational screening of the MLL2 gene among patients diagnosed with Kabuki syndrome. The identification of a large spectrum of MLL2 mutations possibly offers the opportunity to improve the actual knowledge on the clinical basis of this multiple congenital anomalies/mental retardation syndrome, design functional studies to understand the molecular mechanisms underlying this disease, establish genotype-phenotype correlations and improve clinical management.
AB - Background: Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histone methyl transferase MLL2 gene have been identified as its underlying cause. Methods. Genomic DNAs were extracted from 62 index patients clinically diagnosed as affected by Kabuki syndrome. Sanger sequencing was performed to analyze the whole coding region of the MLL2 gene including intron-exon junctions. The putative causal and possible functional effect of each nucleotide variant identified was estimated by in silico prediction tools. Results: We identified 45 patients with MLL2 nucleotide variants. 38 out of the 42 variants were never described before. Consistently with previous reports, the majority are nonsense or frameshift mutations predicted to generate a truncated polypeptide. We also identified 3 indel, 7 missense and 3 splice site. Conclusions: This study emphasizes the relevance of mutational screening of the MLL2 gene among patients diagnosed with Kabuki syndrome. The identification of a large spectrum of MLL2 mutations possibly offers the opportunity to improve the actual knowledge on the clinical basis of this multiple congenital anomalies/mental retardation syndrome, design functional studies to understand the molecular mechanisms underlying this disease, establish genotype-phenotype correlations and improve clinical management.
UR - http://www.scopus.com/inward/record.url?scp=79958047953&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79958047953&partnerID=8YFLogxK
U2 - 10.1186/1750-1172-6-38
DO - 10.1186/1750-1172-6-38
M3 - Article
C2 - 21658225
AN - SCOPUS:79958047953
VL - 6
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
SN - 1750-1172
IS - 1
M1 - 38
ER -