title: Large Duplications Can Be Benign Copy Number Variants: A Case of a 3.6-Mb Xq21.33 Duplication.
abstract: Segmental aneusomies are usually associated with clinical consequences, but an increasing number of nonpathogenic cytogenetically visible as well as large cryptic chromosomal imbalances have been reported. Here, we report a 3.6-Mb Xq21.33 microduplication detected prenatally on a female fetus which was inherited from a phenotypically normal mother and grandfather. It is assumed that male patients harboring Xq or Xp duplication present with syndromic intellectual disability because of functional disomy of the corresponding genes. Female carriers are generally asymptomatic because of preferential inactivation of the abnormal X. In the present case, the 3.6-Mb-duplicated segment encompasses only 2 genes, DIAPH2 and RPL4A. Since the asymptomatic grandfather carries the duplication, we hypothesize that these genes are not dosage sensitive and/or involved in cognitive function. Our observation further illustrates that large copy number variants can be associated with a normal phenotype, especially where gene density is low. Reporting rare cases of large genomic imbalances without a phenotypic effect can be very helpful, especially for genetic counseling in the prenatal setting.
authors.affiliation: Service de Cytogénétique, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Maurin
authors.forename: Chloé
authors.initials: C
authors.lastname: Arfeuille
authors.forename: Pascale
authors.initials: P
authors.lastname: Sonigo
authors.forename: Sophie
authors.initials: S
authors.lastname: Rondeau
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: Catherine
authors.initials: C
authors.lastname: Turleau
authors.forename: Yves
authors.initials: Y
authors.lastname: Ville
authors.forename: Valérie
authors.initials: V
authors.lastname: Malan
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D058674:Chromosome Duplication / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D000080865:Formins; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012269:Ribosomal Proteins / Q000235:genetics; D025064:Sex Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D049951:X Chromosome Inactivation
chemical_list: D002352:Carrier Proteins; C491462:DIAPH2 protein, human; D000080865:Formins; D012269:Ribosomal Proteins; C056368:ribosomal protein L4
keywords: Benign CNV; Duplication Xq21.33; Normal phenotype; Prenatal diagnosis