NF1 microdeletion syndrome: case report of two new patients

Italian Journal of Pediatrics

Ettore Piro¹  Gregorio Serra¹  Vincenzo Antona¹  Giovanni Corsello¹  Federico Zara²  Raffaele Falsaperla³ 

[1] Department of Sciences for Health Promotion and Mother and Child Care “G. D’Alessandro”, University of Palermo;Laboratory of Neurogenetics and Neuroscience, Institute G. Gaslini;Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico-Vittorio Emanuele”;

关键词: NF1 gene;    Atypical deletion;    Genotype-phenotype correlation;    Contiguous gene syndrome;    MLPA;   

DOI  :  10.1186/s13052-019-0718-7

来源: DOAJ

【 摘 要 】

Abstract Background 17q11.2 microdeletions, which include the neurofibromatosis type 1 (NF1) gene region, are responsible for the NF1 microdeletion syndrome, observed in 4.2% of all NF1 patients. Large deletions of the NF1 gene and its flanking regions are associated with a more severe NF1 phenotype than the NF1 general population. Case presentation We hereby describe the clinical and molecular features of two girls (aged 2 and 4 years, respectively), with non-mosaic atypical deletions. Patient 1 showed fifteen café-au-lait spots and axillary freckling, as well as a Lisch nodule in the left eye, strabismus, high-arched palate, malocclusion, severe kyphoscoliosis, bilateral calcaneovalgus foot, mild generalized hypotonia, hyperactivity and deficits of speech-related abilities. NF1 genomic rearrangements through multiplex ligation-dependent probe amplification (MLPA) detected an heterozygous deletion of the whole NF1 gene. Array comparative genomic hybridization (a-CGH) analysis defined a 17q11.2 deletion of about 1 Mb (breakpoints at positions 29,124,299 and 30,151,654), which involved different genes (partially CRLF3, ATAD5, TEFM, ADAP2, RNF135, OMG, EVI2B, EVI2A, RAB11FIP4), including NF1. Patient 2 showed growth and developmental delay, supravalvular pulmonary stenosis, twenty-five café-au-lait spots, axillary freckling, craniofacial dysmorphic features, short neck with pterygium, limb abnormalities and foci of neural dysplasia on brain magnetic resonance imaging (MRI). MLPA detected an heterozygous deletion of NF1, which was detailed by a-CGH indicating the positions 29,124,299 and 30,326,958 as its breakpoints, and which included aside from the genes deleted in Patient 1 also COPRS, UTP6 and partially SUZ12. Fluorescent in situ hybridization (FISH) analysis of the parents documented a de novo origin of the deletions in both cases. Conclusions The present report will likely provide further insights and a better characterization of NF1 microdeletion syndrome.

【 授权许可】

Unknown