title: High frequency of COH1 intragenic deletions and duplications detected by MLPA in patients with Cohen syndrome.
abstract: Cohen syndrome is a rare, clinically variable autosomal recessive disorder characterized by mental retardation, postnatal microcephaly, facial dysmorphisms, ocular abnormalities and intermittent neutropenia. Mutations in the COH1 gene have been found in patients from different ethnic origins. However, a high percentage of patients have only one or no mutated allele. To investigate whether COH1 copy number changes account for missed mutations, we used multiplex ligation-dependent probe amplification (MLPA) to test a group of 14 patients with Cohen syndrome. This analysis has allowed us to identify multi-exonic deletions in 11 alleles and duplications in 4 alleles. Considering our previous study, COH1 copy number variations represent 42% of total mutated alleles. To our knowledge, COH1 intragenic duplications have never been reported in Cohen syndrome. The three duplications encompassed exons 4-13, 20-30 and 57-60, respectively. Interestingly, four deletions showed the same exon coverage (exons 6-16) with respect to a deletion recently reported in a large Greek consanguineous family. Haplotype analysis suggested a possible founder effect in the Mediterranean basin. The use of MLPA was therefore crucial in identifying mutated alleles undetected by traditional techniques and in defining the extent of the deletions/duplications. Given the high percentage of identified copy number variations, we suggest that this technique could be used as the initial screening method for molecular diagnosis of Cohen syndrome.
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Parri
authors.forename: Eleni
authors.initials: E
authors.lastname: Katzaki
authors.forename: Vera
authors.initials: V
authors.lastname: Uliana
authors.forename: Francesca
authors.initials: F
authors.lastname: Scionti
authors.forename: Rossella
authors.initials: R
authors.lastname: Tita
authors.forename: Rosangela
authors.initials: R
authors.lastname: Artuso
authors.forename: Ilaria
authors.initials: I
authors.lastname: Longo
authors.forename: Renske
authors.initials: R
authors.lastname: Boschloo
authors.forename: Raymon
authors.initials: R
authors.lastname: Vijzelaar
authors.forename: Angelo
authors.initials: A
authors.lastname: Selicorni
authors.forename: Francesco
authors.initials: F
authors.lastname: Brancati
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.forename: Seema R
authors.initials: SR
authors.lastname: Lalani
authors.forename: Rita
authors.initials: R
authors.lastname: Grasso
authors.forename: Sabrina
authors.initials: S
authors.lastname: Buoni
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
authors.forename: Laurent
authors.initials: L
authors.lastname: Servais
authors.forename: Bert B A
authors.initials: BB
authors.lastname: de Vries
authors.forename: Nelly
authors.initials: N
authors.lastname: Georgoudi
authors.forename: Sheena
authors.initials: S
authors.lastname: Nakou
authors.forename: Michael B
authors.initials: MB
authors.lastname: Petersen
authors.forename: Francesca
authors.initials: F
authors.lastname: Mari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.forename: Francesca
authors.initials: F
authors.lastname: Ariani
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics; D005385:Fingers / Q000002:abnormalities; D017353:Gene Deletion; D018628:Gene Dosage; D020440:Gene Duplication; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008831:Microcephaly / Q000235:genetics; D008875:Middle Aged; D015336:Molecular Probe Techniques; D009123:Muscle Hypotonia / Q000235:genetics; D009216:Myopia / Q000235:genetics; D009765:Obesity / Q000235:genetics; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins
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