title: An unusual clinical severity of 16p11.2 deletion syndrome caused by unmasked recessive mutation of CLN3.
abstract: With the introduction of array comparative genomic hybridization (aCGH) techniques in the diagnostic setting of patients with developmental delay and congenital malformations, many new microdeletion syndromes have been recognized. One of these recently recognized microdeletion syndromes is the 16p11.2 deletion syndrome, associated with variable clinical outcomes including developmental delay, autism spectrum disorder, epilepsy, and obesity, but also apparently normal phenotype. We report on a 16-year-old patient with developmental delay, exhibiting retinis pigmentosa with progressive visual failure from the age of 9 years, ataxia, and peripheral neuropathy. Chromosomal microarray analysis identified a 1.7-Mb 16p11.2 deletion encompassing the 593-kb common deletion (∼29.5 to ∼30.1 Mb; Hg18) and the 220-kb distal deletion (∼28.74 to ∼28.95 Mb; Hg18) that partially included the CLN3 gene. As the patient's clinical findings were different from usual 16p11.2 microdeletion phenotypes and showed some features reminiscent of juvenile neuronal ceroid-lipofuscinosis (JNCL, Batten disease, OMIM 204200), we suspected and confirmed a mutation of the remaining CLN3 allele. This case further illustrates that unmasking of hemizygous recessive mutations by chromosomal deletion represents one explanation for the phenotypic variability observed in chromosomal deletion disorders.
authors.affiliation: 1] Cytogénétique Médicale, Univ Clermont1, UFR Médecine, CHU Estaing, Clermont-Ferrand, France [2] ERTICa, EA 4677, Univ Clermont1, UFR Médecine, Clermont-Ferrand, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Pebrel-Richard
authors.affiliation: Génétique Médicale, CHU Estaing, Clermont-Ferrand, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Debost-Legrand
authors.affiliation: 1] Cytogénétique Médicale, Univ Clermont1, UFR Médecine, CHU Estaing, Clermont-Ferrand, France [2] ERTICa, EA 4677, Univ Clermont1, UFR Médecine, Clermont-Ferrand, France.
authors.forename: Eléonore
authors.initials: E
authors.lastname: Eymard-Pierre
authors.affiliation: Génétique Médicale, CHU Estaing, Clermont-Ferrand, France.
authors.forename: Victoria
authors.initials: V
authors.lastname: Greze
authors.affiliation: 1] Cytogénétique Médicale, Univ Clermont1, UFR Médecine, CHU Estaing, Clermont-Ferrand, France [2] ERTICa, EA 4677, Univ Clermont1, UFR Médecine, Clermont-Ferrand, France.
authors.forename: Stéphan
authors.initials: S
authors.lastname: Kemeny
authors.affiliation: 1] Cytogénétique Médicale, Univ Clermont1, UFR Médecine, CHU Estaing, Clermont-Ferrand, France [2] ERTICa, EA 4677, Univ Clermont1, UFR Médecine, Clermont-Ferrand, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Gay-Bellile
authors.affiliation: 1] Cytogénétique Médicale, Univ Clermont1, UFR Médecine, CHU Estaing, Clermont-Ferrand, France [2] ERTICa, EA 4677, Univ Clermont1, UFR Médecine, Clermont-Ferrand, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Gouas
authors.affiliation: 1] Cytogénétique Médicale, Univ Clermont1, UFR Médecine, CHU Estaing, Clermont-Ferrand, France [2] ERTICa, EA 4677, Univ Clermont1, UFR Médecine, Clermont-Ferrand, France.
authors.forename: Andreï
authors.initials: A
authors.lastname: Tchirkov
authors.affiliation: 1] Cytogénétique Médicale, Univ Clermont1, UFR Médecine, CHU Estaing, Clermont-Ferrand, France [2] ERTICa, EA 4677, Univ Clermont1, UFR Médecine, Clermont-Ferrand, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vago
authors.affiliation: 1] Cytogénétique Médicale, Univ Clermont1, UFR Médecine, CHU Estaing, Clermont-Ferrand, France [2] ERTICa, EA 4677, Univ Clermont1, UFR Médecine, Clermont-Ferrand, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Goumy
authors.affiliation: Génétique Médicale, CHU Estaing, Clermont-Ferrand, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Francannet
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics*; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D057898:Hemizygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation; D012720:Severity of Illness Index
chemical_list: C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones