title: Diagnosis of familial Wolf-Hirschhorn syndrome due to a paternal cryptic chromosomal rearrangement by conventional and molecular cytogenetic techniques.
abstract: The use of conventional cytogenetic techniques in combination with fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarrays is necessary for the identification of cryptic rearrangements in the diagnosis of chromosomal syndromes. We report two siblings, a boy of 9 years and 9 months of age and his 7-years- and 5-month-old sister, with the classic Wolf-Hirschhorn syndrome (WHS) phenotype. Using high-resolution GTG- and NOR-banding karyotypes, as well as FISH analysis, we characterized a pure 4p deletion in both sibs and a balanced rearrangement in their father, consisting in an insertion of 4p material within a nucleolar organizing region of chromosome 15. Copy number variant (CNV) analysis using SNP arrays showed that both siblings have a similar size of 4p deletion (~6.5 Mb). Our results strongly support the need for conventional cytogenetic and FISH analysis, as well as high-density microarray mapping for the optimal characterization of the genetic imbalance in patients with WHS; parents must always be studied for recognizing cryptic balanced chromosomal rearrangements for an adequate genetic counseling.
authors.affiliation: Servicio de Genética, Hospital General de México, Dr. Balmis No. 148, Colonia Doctores, 06726 México, DF, Mexico.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Venegas-Vega
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández-Ramírez
authors.forename: Luis M
authors.initials: LM
authors.lastname: Zepeda
authors.forename: Karem
authors.initials: K
authors.lastname: Nieto-Martínez
authors.forename: Laura
authors.initials: L
authors.lastname: Gómez-Laguna
authors.forename: Luz M
authors.initials: LM
authors.lastname: Garduño-Zarazúa
authors.forename: Jaime
authors.initials: J
authors.lastname: Berumen
authors.forename: Susana
authors.initials: S
authors.lastname: Kofman
authors.forename: Alicia
authors.initials: A
authors.lastname: Cervantes
mesh_terms: D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D016254:Mutagenesis, Insertional; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D054877:Wolf-Hirschhorn Syndrome / Q000235:genetics* / Q000473:pathology