Clinical and Genetic Findings in Children with Neurofibromatosis Type 1, Legius Syndrome, and Other Related Neurocutaneous Disorders

Genes
Teresa GiuglianoGiulio Piluso

Abstract

Pigmentary manifestations can represent an early clinical sign in children affected by Neurofibromatosis type 1 (NF1), Legius syndrome, and other neurocutaneous disorders. The differential molecular diagnosis of these pathologies is a challenge that can now be met by combining next generation sequencing of target genes with concurrent second-level tests, such as multiplex ligation-dependent probe amplification and RNA analysis. We clinically and genetically investigated 281 patients, almost all pediatric cases, presenting with either NF1 (n = 150), only pigmentary features (café au lait macules with or without freckling; (n = 95), or clinical suspicion of other RASopathies or neurocutaneous disorders (n = 36). The causative variant was identified in 239 out of the 281 patients analyzed (85.1%), while 42 patients remained undiagnosed (14.9%). The NF1 and SPRED1 genes were mutated in 73.3% and 2.8% of cases, respectively. The remaining 8.9% carried mutations in different genes associated with other disorders. We achieved a molecular diagnosis in 69.5% of cases with only pigmentary manifestations, allowing a more appropriate clinical management of these patients. Our findings, together with the increasing availability and sharing ...Continue Reading

References

Jul 1, 1985·American Journal of Medical Genetics·J E AllansonM I Van Allen
Jul 1, 1985·American Journal of Medical Genetics·J M Opitz, D D Weaver
Jan 1, 1996·Journal of Medical Genetics·M H ShenM Upadhyaya
Apr 26, 2000·European Journal of Human Genetics : EJHG·M LuijtenT J Hulsebos
Jan 11, 2000·Nucleic Acids Research·S T SherryK Sirotkin
Aug 9, 2001·Nature·T WakiokaA Yoshimura
Mar 28, 2003·American Journal of Human Genetics·T De RaedtE Legius
Jun 11, 2005·American Journal of Medical Genetics. Part a·Debora R BertolaJosé Eduardo Krieger
Dec 29, 2005·American Journal of Human Genetics·Alessandro De LucaBruno Dallapiccola
Sep 1, 2006·Familial Cancer·Siân GriffithsMeena Upadhyaya
Sep 8, 2006·European Journal of Human Genetics : EJHG·Rosalie E Ferner
Sep 29, 2006·The New England Journal of Medicine·Peter B CrinoElizabeth Petri Henske
Jun 14, 2008·Journal of Medical Genetics·E DenayerE Legius
Aug 30, 2008·Lancet·Paolo CuratoloSergiusz Jozwiak
Oct 18, 2008·Nucleic Acids Research·Kim D PruittDonna R Maglott
Jan 2, 2009·Pediatrics·Virginia C WilliamsBernard L Maria
May 19, 2009·American Journal of Medical Genetics. Part a·Christian ThielAnita Rauch
May 27, 2009·Current Opinion in Genetics & Development·William E Tidyman, Katherine A Rauen
Oct 28, 2009·Genome Research·Katherine S PollardAdam Siepel
Nov 19, 2009·JAMA : the Journal of the American Medical Association·Ludwine MessiaenEric Legius
Dec 23, 2009·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Kimberly Jett, Jan M Friedman
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jun 1, 2010·Human Mutation·Eric PasmantUNKNOWN members of the NF France Network
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Oct 21, 2010·Annals of the New York Academy of Sciences·Marco Tartaglia, Bruce D Gelb
Oct 29, 2010·Nature·Gonçalo R AbecasisGil A McVean
Mar 1, 2011·The Journal of Molecular Diagnostics : JMD·María Carmen ValeroConcepción Hernández-Chico
Nov 23, 2011·The Journal of Clinical Investigation·Hsiao-Fang WangYi-Ping Hsueh
Apr 1, 2014·Nature Methods·Jana Marie SchwarzDominik Seelow
Apr 29, 2014·BMC Medical Genetics·Claudia SantoroSilverio Perrotta

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Citations

Aug 11, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Juan A Perez-ValenciaKatharina Wimmer
Jan 15, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Filiz HazanAjlan Tükün
Feb 11, 2021·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Alessandra D'AmicoDaniela Melis
Mar 6, 2021·Italian Journal of Pediatrics·Valentina OrlandiFranco Antoniazzi

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Methods Mentioned

BETA
electrophoresis
Illumina sequencing
PCR
DNA Assay

Software Mentioned

SIFT
STRING
. Net
Genome Analysis Toolkit ( GATK )
ExAC browsers
Coffalyser
Polyphen
Holland
Primer
Mutation Taster

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