PMID- 33415784
OWN - NLM
STAT- MEDLINE
DCOM- 20210803
LR  - 20210803
IS  - 1552-4833 (Electronic)
IS  - 1552-4825 (Linking)
VI  - 185
IP  - 4
DP  - 2021 Apr
TI  - Clinical diagnosis of neurofibromatosis type I in multiple family members due to 
      cosegregation of a unique balanced translocation with disruption of the NF1 
      locus: Testing considerations for accurate diagnosis.
PG  - 1222-1227
LID - 10.1002/ajmg.a.62071 [doi]
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that causes a 
      predisposition to develop tumors along the peripheral nervous system. The NF1 
      gene, located at 17q11.2, has the highest mutation rate among known human genes 
      and about half of NF1 patients have de novo pathogenic variants. We present a 
      case of clinical NF1 diagnoses in multiple family members with phenotypes ranging 
      from mild to severe. Chromosome analysis of the 3-year-old female proband with 
      NF1 resulted in an abnormal karyotype that was inherited from her mother: 
      46,XX,t(4;17)(q21.3;q11.2) mat. However, no NF1 genetic variants were identified 
      by either NGS analysis of NF1 DNA coding regions, deletion-duplication studies, 
      or by cytogenomic microarray copy number analysis. Follow-up chromosome studies 
      of the proband's two male siblings demonstrated cosegregation of the same 
      balanced translocation and a clinical diagnosis of NF1. Based on the 
      cosegregation of the translocation with the NF1 clinical presentation in this 
      family, we hypothesized that the NF1 gene may have been disrupted by this unique 
      rearrangement. Subsequent fluorescence in situ hybridization (FISH) analysis of 
      the metaphase cells of an affected sibling revealed a disruption of the NF1 gene 
      confirming the underlying basis of the clinical NF1 presentation in this family. 
      The utilization of traditional cytogenetic as well as evolving molecular methods 
      was not only pivotal in the diagnosis of NF1 and management for this family, but 
      is also pertinent to other patients with a family history of NF1.
CI  - (c) 2021 Wiley Periodicals LLC.
FAU - Smith, Rebecca B
AU  - Smith RB
AUID- ORCID: 0000-0001-7705-5729
AD  - Department of Pathology, Microbiology, and Immunology, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
AD  - Genetics Associates Inc., Nashville, Tennessee, USA.
FAU - Solem, Emily P
AU  - Solem EP
AD  - Department of Pediatrics, Vanderbilt University Medical Center, Nashville, 
      Tennessee, USA.
FAU - Metz, Emma C
AU  - Metz EC
AD  - Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
FAU - Wheeler, Ferrin C
AU  - Wheeler FC
AD  - Department of Pathology, Microbiology, and Immunology, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
AD  - Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
FAU - Phillips, John A 3rd
AU  - Phillips JA 3rd
AD  - Department of Pathology, Microbiology, and Immunology, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
AD  - Department of Pediatrics, Vanderbilt University Medical Center, Nashville, 
      Tennessee, USA.
FAU - Yenamandra, Ashwini
AU  - Yenamandra A
AD  - Department of Pathology, Microbiology, and Immunology, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
AD  - Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
LA  - eng
PT  - Case Reports
DEP - 20210108
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
RN  - 0 (NF1 protein, human)
RN  - 0 (Neurofibromin 1)
SB  - IM
MH  - Child, Preschool
MH  - *Cytogenetic Analysis
MH  - Female
MH  - Genetic Testing/methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotype
MH  - Neurofibromatosis 1/*diagnosis/genetics/pathology
MH  - Neurofibromin 1/*genetics
MH  - Translocation, Genetic/*genetics
OTO - NOTNLM
OT  - FISH
OT  - NF1
OT  - balanced translocation
OT  - familial translocation
OT  - family history of NF1
OT  - neurofibromatosis type 1
EDAT- 2021/01/09 06:00
MHDA- 2021/08/04 06:00
CRDT- 2021/01/08 06:19
PHST- 2020/12/13 00:00 [revised]
PHST- 2020/06/23 00:00 [received]
PHST- 2020/12/19 00:00 [accepted]
PHST- 2021/01/09 06:00 [pubmed]
PHST- 2021/08/04 06:00 [medline]
PHST- 2021/01/08 06:19 [entrez]
AID - 10.1002/ajmg.a.62071 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2021 Apr;185(4):1222-1227. doi: 10.1002/ajmg.a.62071. Epub 2021 
      Jan 8.