Neurofibromatosis type 1 diagnostic study of choice: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
Line 3: Line 3:
{{CMG}}; {{AE}}[[User:MoisesRomo|Moises Romo M.D.]]
{{CMG}}; {{AE}}[[User:MoisesRomo|Moises Romo M.D.]]
== Overview ==
== Overview ==
NF1 is often diagnosed early on in childhood.<ref name="pmid26860753">{{cite journal |vauthors=Rad E, Tee AR |title=Neurofibromatosis type 1: Fundamental insights into cell signalling and cancer |journal=Semin. Cell Dev. Biol. |volume=52 |issue= |pages=39–46 |date=April 2016 |pmid=26860753 |doi=10.1016/j.semcdb.2016.02.007 |url=}}</ref>
 
* '''[[Neurofibromatosis type 1]]''' is mainly diagnosed clinically.<ref name="pmid26564071" />
* [[Neurofibromatosis type 1]] is usually diagnosed early on in [[childhood]].<ref name="pmid26860753">{{cite journal |vauthors=Rad E, Tee AR |title=Neurofibromatosis type 1: Fundamental insights into cell signalling and cancer |journal=Semin. Cell Dev. Biol. |volume=52 |issue= |pages=39–46 |date=April 2016 |pmid=26860753 |doi=10.1016/j.semcdb.2016.02.007 |url=}}</ref>
* [[Genetic testing]] may be necessary in difficult cases.<ref name="pmid26564071" />


== Diagnostic Study of Choice ==
== Diagnostic Study of Choice ==


=== Study of choice ===
=== Study of choice ===
The diagnosis of neurofibromatosis type 1 is mainly clinical.<ref name="pmid26564071">{{cite journal |vauthors=Anderson JL, Gutmann DH |title=Neurofibromatosis type 1 |journal=Handb Clin Neurol |volume=132 |issue= |pages=75–86 |date=2015 |pmid=26564071 |doi=10.1016/B978-0-444-62702-5.00004-4 |url=}}</ref>
Approximately 46% of individuals with a ''de novo'' mutation of NF1 gene do not meet criteria the first year of life.<ref name="pmid31582003" />


Annual monitoring until late childhood is necessary for patients with suspicious neurofibromatosis type 1.<ref name="pmid31582003" />
* [[NF1]] is often diagnosed early on in [[childhood]].<ref name="pmid26860753" />


97% of children with one or more features of neurofibromatosis type 1 meet diagnostic criteria by age 8 years.<ref name="pmid31582003">{{cite journal |vauthors=Ly KI, Blakeley JO |title=The Diagnosis and Management of Neurofibromatosis Type 1 |journal=Med. Clin. North Am. |volume=103 |issue=6 |pages=1035–1054 |date=November 2019 |pmid=31582003 |doi=10.1016/j.mcna.2019.07.004 |url=}}</ref>
* The diagnosis of [[neurofibromatosis type 1]] is mainly clinical.<ref name="pmid26564071">{{cite journal |vauthors=Anderson JL, Gutmann DH |title=Neurofibromatosis type 1 |journal=Handb Clin Neurol |volume=132 |issue= |pages=75–86 |date=2015 |pmid=26564071 |doi=10.1016/B978-0-444-62702-5.00004-4 |url=}}</ref>
* Approximately 46% of individuals with a ''[[de novo]]'' [[mutation]] of [[NF1]] [[gene]] do not meet criteria the first year of life.<ref name="pmid31582003" />
* Annual monitoring until late [[Child development|childhood]] is necessary for patients with suspicious [[neurofibromatosis type 1]].<ref name="pmid31582003" />
* 97% of children with one or more features of [[Neurofibromatosis type 1|neurofibromatosis type]] 1 meet diagnostic criteria by age 8 years.<ref name="pmid31582003">{{cite journal |vauthors=Ly KI, Blakeley JO |title=The Diagnosis and Management of Neurofibromatosis Type 1 |journal=Med. Clin. North Am. |volume=103 |issue=6 |pages=1035–1054 |date=November 2019 |pmid=31582003 |doi=10.1016/j.mcna.2019.07.004 |url=}}</ref>


=== National Institute of Health (NIH) Diagnostic Criteria ===
=== National Institute of Health (NIH) Diagnostic Criteria ===
2 of the following 7 "Cardinal Clinical Features" are required for positive diagnosis:<ref name="pmid9207339">{{cite journal |vauthors=Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D |title=The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2 |journal=JAMA |volume=278 |issue=1 |pages=51–7 |date=July 1997 |pmid=9207339 |doi= |url=}}</ref><ref name="pmid3152465">{{cite journal |vauthors= |title=National Institutes of Health Consensus Development Conference Statement: neurofibromatosis. Bethesda, Md., USA, July 13-15, 1987 |journal=Neurofibromatosis |volume=1 |issue=3 |pages=172–8 |date=1988 |pmid=3152465 |doi= |url=}}</ref>
2 of the following 7 "Cardinal Clinical Features" are required for positive [[diagnosis]]:<ref name="pmid9207339">{{cite journal |vauthors=Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D |title=The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2 |journal=JAMA |volume=278 |issue=1 |pages=51–7 |date=July 1997 |pmid=9207339 |doi= |url=}}</ref><ref name="pmid3152465">{{cite journal |vauthors= |title=National Institutes of Health Consensus Development Conference Statement: neurofibromatosis. Bethesda, Md., USA, July 13-15, 1987 |journal=Neurofibromatosis |volume=1 |issue=3 |pages=172–8 |date=1988 |pmid=3152465 |doi= |url=}}</ref><ref name="pmid26564071" />


*6 or more café-au-lait macules over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals
*6 or more [[Café-au-lait spot|café-au-lait macules]] over 5 mm in greatest diameter in pre-[[Puberty|pubertal]] individuals and over 15 mm in greatest diameter in post-[[Puberty|pubertal]] individuals
*2 or more neurofibromas of any type or 1 plexiform neurofibroma
*2 or more [[Neurofibroma|neurofibromas]] of any type or 1 [[plexiform neurofibroma]]
*Freckling in the axillary or inguinal regions
*Freckling in the [[axillary]] or [[Inguinal region|inguinal regions]]
*Optic glioma
*[[Optic nerve glioma|Optic glioma]]
*2 or more [[Lisch nodules]] (iris harmartomas)
*2 or more [[Lisch nodules]] (iris harmartomas)
*A distinctive osseous lesion such as sphenoid dysplasia or thinning of the long bone cortex with or without pseudarthrosis
*A distinctive [[osseous]] lesion such as [[Sphenoid bone|sphenoid]] [[dysplasia]] or thinning of the long [[bone cortex]] with or without [[pseudarthrosis]]
*A first degree relative (parent, sibling, or offspring) with NF1 by the above criteria
*A first degree relative (parent, sibling, or offspring) with [[NF1]] by the above criteria


=== Genetic testing ===
=== Genetic testing ===
In rare occassions where diagnosis is unclear, genetic testing may be necessary.<ref name="pmid26564071" />
==== The comparison of various diagnostic studies for [disease name] ====
{|
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
! style="background: #4479BA; color: #FFFFFF; text-align: center;" | Test
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Sensitivity
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Specificity
|-
! style="background: #696969; color: #FFFFFF; text-align: center;" |Test 1
| style="background: #DCDCDC; padding: 5px; text-align: center;" |...%
| style="background: #DCDCDC; padding: 5px; text-align: center;" |...%
|-
! style="background: #696969; color: #FFFFFF; text-align: center;" |Test 2
| style="background: #DCDCDC; padding: 5px; text-align: center;" |...%
| style="background: #DCDCDC; padding: 5px; text-align: center;" |...%
|}
Disorders that have overlapping features with neurofibromatosis type 1 should be considered in the differential diagnosis, which can include Legius syndrome, skin hyperpigmentation, mismatch repair and overgrowth syndromes and from tumours that are misidentified as neurofibromas (lipomas). Mutations in SPRED1 cause Legius syndrome, which is characterized by CALMs, skinfold freckling, learning difficulties and macrocephaly, but not neurofibromas, Lisch nodules or central nervous system tumours.<ref name="pmid28230061">{{cite journal |vauthors=Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ |title=Neurofibromatosis type 1 |journal=Nat Rev Dis Primers |volume=3 |issue= |pages=17004 |date=February 2017 |pmid=28230061 |doi=10.1038/nrdp.2017.4 |url=}}</ref><ref name="pmid19920235">{{cite journal |vauthors=Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, Spencer E, Arn P, Babovic-Vuksanovic D, Bay C, Bobele G, Cohen BH, Escobar L, Eunpu D, Grebe T, Greenstein R, Hachen R, Irons M, Kronn D, Lemire E, Leppig K, Lim C, McDonald M, Narayanan V, Pearn A, Pedersen R, Powell B, Shapiro LR, Skidmore D, Tegay D, Thiese H, Zackai EH, Vijzelaar R, Taniguchi K, Ayada T, Okamoto F, Yoshimura A, Parret A, Korf B, Legius E |title=Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome |journal=JAMA |volume=302 |issue=19 |pages=2111–8 |date=November 2009 |pmid=19920235 |doi=10.1001/jama.2009.1663 |url=}}</ref> Genetic testing can help to differentiate between a diagnosis of neurofibromatosis type 1 and Legius syndrome. Importantly, neurofibromatosis type 1 is clinically and genetically distinct from other rare tumour predisposition conditions, such as neurofibromatosis type 2 (which is caused by mutations in NF2)<ref name="pmid28230061" /><ref name="pmid8453669">{{cite journal |vauthors=Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K |title=A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor |journal=Cell |volume=72 |issue=5 |pages=791–800 |date=March 1993 |pmid=8453669 |doi=10.1016/0092-8674(93)90406-g |url=}}</ref> and from schwannomatosis (which is associated with mutations in SMARCB1 or LZTR1)101,102.<ref name="pmid28230061" /><ref name="pmid17357086">{{cite journal |vauthors=Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P |title=Germline mutation of INI1/SMARCB1 in familial schwannomatosis |journal=Am. J. Hum. Genet. |volume=80 |issue=4 |pages=805–10 |date=April 2007 |pmid=17357086 |pmc=1852715 |doi=10.1086/513207 |url=}}</ref>
The National Institute of Health (NIH) has created specific criteria for the diagnosis of NF-1.  Two of these seven "Cardinal Clinical Features" are required for positive diagnosis.<ref>Huson SM, Hughes RAC. The Neurofibromatoses. London, UK: Chapman and Hall; 1994;1.3.2:9</ref>


*
* In rare occassions where diagnosis is unclear, [[genetic testing]] may be necessary.<ref name="pmid26564071" />
* Hundreds of [[Mutation|mutations]] in the ''[[NF1]]'' [[gene]] have beenrecognized; these may be [[Deletion (genetics)|deletions]], [[Insertion|insertions]], [[Splice site mutation|splice site mutations]], [[amino acid]] substitutions, full [[gene]] [[Deletion (genetics)|deletions]] and chromosomal rearrangements.<ref name="pmid12566521">{{cite journal |vauthors=Messiaen L, Riccardi V, Peltonen J, Maertens O, Callens T, Karvonen SL, Leisti EL, Koivunen J, Vandenbroucke I, Stephens K, Pöyhönen M |title=Independent NF1 mutations in two large families with spinal neurofibromatosis |journal=J. Med. Genet. |volume=40 |issue=2 |pages=122–6 |date=February 2003 |pmid=12566521 |pmc=1735368 |doi=10.1136/jmg.40.2.122 |url=}}</ref><ref name="pmid17636453" />
* [[Genetic testing]] may be necessary for differentiating [[neurofibromatosis type 1]] and [[Legius syndrome]].<ref name="pmid28230061">{{cite journal |vauthors=Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ |title=Neurofibromatosis type 1 |journal=Nat Rev Dis Primers |volume=3 |issue= |pages=17004 |date=February 2017 |pmid=28230061 |doi=10.1038/nrdp.2017.4 |url=}}</ref><ref name="pmid8453669">{{cite journal |vauthors=Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K |title=A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor |journal=Cell |volume=72 |issue=5 |pages=791–800 |date=March 1993 |pmid=8453669 |doi=10.1016/0092-8674(93)90406-g |url=}}</ref>
* [[NF1]] [[gene]] ''[[de novo]]'' [[mutations]] seem to occur mostly on paternal chromosomes.<ref name="pmid9143926">{{cite journal |vauthors=Ainsworth PJ, Chakraborty PK, Weksberg R |title=Example of somatic mosaicism in a series of de novo neurofibromatosis type 1 cases due to a maternally derived deletion |journal=Hum. Mutat. |volume=9 |issue=5 |pages=452–7 |date=1997 |pmid=9143926 |doi=10.1002/(SICI)1098-1004(1997)9:5<452::AID-HUMU12>3.0.CO;2-1 |url=}}</ref><ref name="pmid9654211">{{cite journal |vauthors=Upadhyaya M, Ruggieri M, Maynard J, Osborn M, Hartog C, Mudd S, Penttinen M, Cordeiro I, Ponder M, Ponder BA, Krawczak M, Cooper DN |title=Gross deletions of the neurofibromatosis type 1 (NF1) gene are predominantly of maternal origin and commonly associated with a learning disability, dysmorphic features and developmental delay |journal=Hum. Genet. |volume=102 |issue=5 |pages=591–7 |date=May 1998 |pmid=9654211 |doi=10.1007/s004390050746 |url=}}</ref>
* [[Neurofibromatosis type 1]] is clinically and genetically different from certain tumour predisposition conditions, such as [[neurofibromatosis type 2]] and [[schwannomatosis]].<ref name="pmid28230061" /><ref name="pmid17357086">{{cite journal |vauthors=Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P |title=Germline mutation of INI1/SMARCB1 in familial schwannomatosis |journal=Am. J. Hum. Genet. |volume=80 |issue=4 |pages=805–10 |date=April 2007 |pmid=17357086 |pmc=1852715 |doi=10.1086/513207 |url=}}</ref><ref name="pmid19920235">{{cite journal |vauthors=Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, Spencer E, Arn P, Babovic-Vuksanovic D, Bay C, Bobele G, Cohen BH, Escobar L, Eunpu D, Grebe T, Greenstein R, Hachen R, Irons M, Kronn D, Lemire E, Leppig K, Lim C, McDonald M, Narayanan V, Pearn A, Pedersen R, Powell B, Shapiro LR, Skidmore D, Tegay D, Thiese H, Zackai EH, Vijzelaar R, Taniguchi K, Ayada T, Okamoto F, Yoshimura A, Parret A, Korf B, Legius E |title=Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome |journal=JAMA |volume=302 |issue=19 |pages=2111–8 |date=November 2009 |pmid=19920235 |doi=10.1001/jama.2009.1663 |url=}}</ref>
* [[Genetic testing]] detects approximately 95% of [[NF1]] mutations in patients that fulfill the clinical diagnostic criteria.<ref name="pmid10862084">{{cite journal |vauthors=Messiaen LM, Callens T, Mortier G, Beysen D, Vandenbroucke I, Van Roy N, Speleman F, Paepe AD |title=Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects |journal=Hum. Mutat. |volume=15 |issue=6 |pages=541–55 |date=2000 |pmid=10862084 |doi=10.1002/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N |url=}}</ref><ref name="pmid17636453">{{cite journal |vauthors=Radtke HB, Sebold CD, Allison C, Haidle JL, Schneider G |title=Neurofibromatosis type 1 in genetic counseling practice: recommendations of the National Society of Genetic Counselors |journal=J Genet Couns |volume=16 |issue=4 |pages=387–407 |date=August 2007 |pmid=17636453 |pmc=6338721 |doi=10.1007/s10897-007-9101-8 |url=}}</ref>
* [[Genetic testing]] does not predict or determines the severity the condition.<ref name="pmid17636453" />
* A negative [[DNA]] result does not exclude the [[mutation]] when there is a known familial mutation.<ref name="pmid17636453" /><br />


The diagnostic criteria for NF1 were first established by the NIH Consensus Development panel in 1987 (National Institutes of Health Consensus Development Conference, 1988) and updated in 1997 (Gutmann et al., 1997). To make the diagnosis of NF1, two of the following clinical features are required: ● six or more cafe´-au-lait macules with diameters greater than 5 mm in a prepubertal patient and greater than 15 mm in a postpubertal patient ● two or more neurofibromas or one plexiform neurofibroma ● skinfold (axillary or inguinal) freckling ● optic pathway tumor ● two or more iris hamartomas ● characteristic bony lesion ● first-degree relative with neurofibromatosis type 1<ref name="pmid26564071" />
<br />


==References==
==References==

Revision as of 04:12, 1 July 2020

Neurofibromatosis type 1 Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Neurofibromatosis type 1 from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Interventions

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Neurofibromatosis type 1 diagnostic study of choice On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Neurofibromatosis type 1 diagnostic study of choice

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Neurofibromatosis type 1 diagnostic study of choice

CDC on Neurofibromatosis type 1 diagnostic study of choice

Neurofibromatosis type 1 diagnostic study of choice in the news

Blogs on Neurofibromatosis type 1 diagnostic study of choice

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Neurofibromatosis type 1 diagnostic study of choice

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo M.D.

Overview

Diagnostic Study of Choice

Study of choice

National Institute of Health (NIH) Diagnostic Criteria

2 of the following 7 "Cardinal Clinical Features" are required for positive diagnosis:[4][5][1]

Genetic testing


References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Anderson JL, Gutmann DH (2015). "Neurofibromatosis type 1". Handb Clin Neurol. 132: 75–86. doi:10.1016/B978-0-444-62702-5.00004-4. PMID 26564071.
  2. ↑ 2.0 2.1 Rad E, Tee AR (April 2016). "Neurofibromatosis type 1: Fundamental insights into cell signalling and cancer". Semin. Cell Dev. Biol. 52: 39–46. doi:10.1016/j.semcdb.2016.02.007. PMID 26860753.
  3. ↑ 3.0 3.1 3.2 Ly KI, Blakeley JO (November 2019). "The Diagnosis and Management of Neurofibromatosis Type 1". Med. Clin. North Am. 103 (6): 1035–1054. doi:10.1016/j.mcna.2019.07.004. PMID 31582003.
  4. ↑ Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D (July 1997). "The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2". JAMA. 278 (1): 51–7. PMID 9207339.
  5. ↑ "National Institutes of Health Consensus Development Conference Statement: neurofibromatosis. Bethesda, Md., USA, July 13-15, 1987". Neurofibromatosis. 1 (3): 172–8. 1988. PMID 3152465.
  6. ↑ Messiaen L, Riccardi V, Peltonen J, Maertens O, Callens T, Karvonen SL, Leisti EL, Koivunen J, Vandenbroucke I, Stephens K, Pöyhönen M (February 2003). "Independent NF1 mutations in two large families with spinal neurofibromatosis". J. Med. Genet. 40 (2): 122–6. doi:10.1136/jmg.40.2.122. PMC 1735368. PMID 12566521.
  7. ↑ 7.0 7.1 7.2 7.3 Radtke HB, Sebold CD, Allison C, Haidle JL, Schneider G (August 2007). "Neurofibromatosis type 1 in genetic counseling practice: recommendations of the National Society of Genetic Counselors". J Genet Couns. 16 (4): 387–407. doi:10.1007/s10897-007-9101-8. PMC 6338721. PMID 17636453.
  8. ↑ 8.0 8.1 Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ (February 2017). "Neurofibromatosis type 1". Nat Rev Dis Primers. 3: 17004. doi:10.1038/nrdp.2017.4. PMID 28230061.
  9. ↑ Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K (March 1993). "A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor". Cell. 72 (5): 791–800. doi:10.1016/0092-8674(93)90406-g. PMID 8453669.
  10. ↑ Ainsworth PJ, Chakraborty PK, Weksberg R (1997). "Example of somatic mosaicism in a series of de novo neurofibromatosis type 1 cases due to a maternally derived deletion". Hum. Mutat. 9 (5): 452–7. doi:10.1002/(SICI)1098-1004(1997)9:5<452::AID-HUMU12>3.0.CO;2-1. PMID 9143926.
  11. ↑ Upadhyaya M, Ruggieri M, Maynard J, Osborn M, Hartog C, Mudd S, Penttinen M, Cordeiro I, Ponder M, Ponder BA, Krawczak M, Cooper DN (May 1998). "Gross deletions of the neurofibromatosis type 1 (NF1) gene are predominantly of maternal origin and commonly associated with a learning disability, dysmorphic features and developmental delay". Hum. Genet. 102 (5): 591–7. doi:10.1007/s004390050746. PMID 9654211.
  12. ↑ Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P (April 2007). "Germline mutation of INI1/SMARCB1 in familial schwannomatosis". Am. J. Hum. Genet. 80 (4): 805–10. doi:10.1086/513207. PMC 1852715. PMID 17357086.
  13. ↑ Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, Spencer E, Arn P, Babovic-Vuksanovic D, Bay C, Bobele G, Cohen BH, Escobar L, Eunpu D, Grebe T, Greenstein R, Hachen R, Irons M, Kronn D, Lemire E, Leppig K, Lim C, McDonald M, Narayanan V, Pearn A, Pedersen R, Powell B, Shapiro LR, Skidmore D, Tegay D, Thiese H, Zackai EH, Vijzelaar R, Taniguchi K, Ayada T, Okamoto F, Yoshimura A, Parret A, Korf B, Legius E (November 2009). "Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome". JAMA. 302 (19): 2111–8. doi:10.1001/jama.2009.1663. PMID 19920235.
  14. ↑ Messiaen LM, Callens T, Mortier G, Beysen D, Vandenbroucke I, Van Roy N, Speleman F, Paepe AD (2000). "Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects". Hum. Mutat. 15 (6): 541–55. doi:10.1002/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N. PMID 10862084.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Neurofibromatosis_type_1_diagnostic_study_of_choice&oldid=1620077"