title: Exome sequencing in a patient with Catel-Manzke-like syndrome excludes the involvement of the known genes and reveals a possible candidate.
abstract: In the present study we describe the exome sequencing and analysis of a patient with Catel-Manzke-like phenotype showing bilateral hyperphalangism of the second finger and thumb clinodactyly due to a unilateral delta phalanx, associated with growth, cardiac and vertebral defects. The exome sequencing analysis excluded pathogenetic mutations in the genes known to cause syndromes with hyperphalangism and did not identify any alteration in the X-chromosome or de novo mutations in likely candidate genes. Under the assumption of an autosomal recessive mode of inheritance and based on the frequency of the single nucleotide variants found in homozygous or double heterozygous states and the results of computer prediction programs, only one gene, DNAH10, emerged as a candidate in the pathogenesis of the disease in our patient. However, the differences among the known biological functions of DNAH10 and the genes involved in the other syndromes with hyperphalangism, suggest caution in the interpretation of the results.
authors.affiliation: Medical Genetics, Department of Medical and Surgical Sciences, University Hospital of Modena, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Stanghellini
authors.affiliation: Laboratory of Translational Genomics, Centre for Integrative Biology, University of Trento, Italy.
authors.forename: Erik
authors.initials: E
authors.lastname: Dassi
authors.affiliation: NGS Facility, Laboratory of Biomolecular Sequence and Structure Analysis for Health, Centre for Integrative Biology, University of Trento, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bertorelli
authors.affiliation: NGS Facility, Laboratory of Biomolecular Sequence and Structure Analysis for Health, Centre for Integrative Biology, University of Trento, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: De Sanctis
authors.affiliation: Division of Internal Medicine and Centre for Haemochromatosis, University Hospital of Modena, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Caleffi
authors.affiliation: Hand Surgery and Microsurgery, Department of Locomotor System Diseases, University Hospital of Modena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Landi
authors.affiliation: Medical Genetics, Department of Medical and Surgical Sciences, University Hospital of Modena, Italy. Electronic address: percesepe.antonio@unimo.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Percesepe
mesh_terms: D000595:Amino Acid Sequence; D004398:Dyneins / Q000235:genetics*; D059472:Exome; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010855:Pierre Robin Syndrome / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D004398:Dyneins
keywords: Congenital hand deformities; High-throughput sequencing; Rare diseases