A novel de novo microdeletion at 17q11.2 adjacent to NF1 gene associated with developmental delay, short stature, microcephaly and dysmorphic features

Abstract

BackgroundMicrodeletions at 17q11.2 often encompass NF1 gene, is the cause for NF1 microdeletion syndrome. Microdeletion at 17q11.2 without the involvement of NF1 gene is rarely reported.Case presentationHere we reported a patient carrying a novel de novo deletion at 17q11.2 adjacent to NF1 gene, who presented with developmental delay, short stature, postnatal microcephaly, underweight and dysmorphic features including flat facial profile, dolicocephaly, hypertelorism, short philtrum, flat nasal bridge and posteriorly rotated and low set ears. Chromosomal microarray analysis revealed a 1.69 Mb de novo deletion at 17q11.2 adjacent to NF1 gene, which involves 43 RefSeq genes. We compared this with four overlapping deletions at this interval.ConclusionsA rare de novo microdeletion at 17q11.2 not involving NF1 gene is associated with developmental delay and dysmorphic features. Seven genes, TAOK1, PHF12, NUFIP2, SLC26A4, SEZ6, GIT1 and TRAF4 are possible candidates for the clinical features of our patient. The delineation of this rare deletion and description of associated clinical phenotypes will help to understand the genotype-phenotype correlation of genomic imbalances at this locus.

Rare NF1 microdeletion syndrome in an Omani patient

“…It is not surprising that patients with mutations in the NF1 gene can also present with features overlapping with those seen in NS patients, considering that both the NF1 gene and the NS genes express proteins which are integral components of the RAS‐MAPK developmental pathways during embryogenesis . Also, the complete loss of one of the alleles of the NF1 gene is the probable cause of the relatively more severe and earlier presentation of cognitive abnormalities and dysmorphism in our patient, a phenomenon also observed in previous reports of NF1 microdeletions …”

“…4 Also, the complete loss of one of the alleles of the NF1 gene is the probable cause of the relatively more severe and earlier presentation of cognitive abnormalities and dysmorphism in our patient, a phenomenon also observed in previous reports of NF1 microdeletions. [5][6][7][8][9] Although SNP analysis using array CGH indicated that the microdeleted allele was maternal in origin, no genomic abnormality was detected in either parent. Hence, we concluded that this 1.7 Mb microdeletion within the 17q11.2 region probably occurred as a de novo event.…”

NF1 microdeletion syndrome: case report of two new patients

“…17q11.2 microdeletions, encompassing NF1 gene, are responsible for NF1 microdeletion syndrome [5], which include dysmorphic features, neurodevelopmental delay, cardiovascular defects, overgrowth, a higher tumor burden and earlier onset of benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST)/other malignancies [2]. It represents 4.2% of all NF1 patients.…”

“…To estimate the likely effect of the deleted genes, the probability of loss-of-function (LoF) intolerance should be considered, differentiating genes in LoF intolerant or tolerant [2]. Specifically, 5 genes ( CRLF3 , ATAD5 , RAB11FIP4 , SUZ12 and LRRC37B ) were predicted to be LoF intolerant [2], which means that they could have clinical consequences if present in one copy [5]; 4 of them (2 partially) are deleted in our subjects.…”

De Novo Variants in TAOK1 Cause Neurodevelopmental Disorders

“…A microdeletion on chromosome 17, comprising TAOK1, had nominated TAOK1 as a potential candidate gene for developmental delay and microcephaly. 26 The Decipher database reports four additional patients with large deletions that include the TAOK1 gene. These patients include one who has an intragenic deletion of exons 2-8 and a reported phenotype of microcephaly and seizures.…”