Table 1
Mutations found in the patients and their clinical features.
| # | Sex-Age | NIH Criteria | Additional Findings | Pathogenic Variant (NM_000267) | Genetic Analysis | Ref. |
|---|---|---|---|---|---|---|
| #1 | M-3 | a; f | none | c.311T>G; p.(Leu104Ter) | NA | [18] |
| #2 | F-13 | a | learning disability | c.731-1G>C | NA | [19] |
| #3 | M-7 | a; b; e; g | none | c.1541_1542delAG; p.(Gln514Argfs) | NA | [20] |
| #4 | M-1 | a | none | c.2693C>T; p.Leu898Pro | NA | [21] |
| #5 | M-7 | a; b; g | none | c.3113+1G>C | NA | [12] |
| #6 | F-8 | a; c; g | T2 flair hyperintense signals in left globus palliadus level | c.3230_3230delT; p.(Ser1078Hisfs*3) | NA | This report |
| #7 | F-52 | a; b; d | none | c.3709-2A>G | NA | [22] |
| #8 | F-7 mths | a; b; f; g | none | c.4082delT; p.Leu1601Cysfs*2) | paternally inherited | [12] |
| #9 | M-41 | a; b | none | c.4867G>C; p.(Asp1623His) | NA | [12] |
| #10 | M-7 | a; d | surgery due to severe bowel obstruction; T2 flair hyper-intense signals in both cerebellar hemispheres | c.5389C>T; p.(Arg1947Ter) | NA | [23] |
| #11 | F-17 | a; e | coroidal coloboma on the left eye | c.5546+5G>A | NA | [18] |
| #12 | F-2 | a | convulsion | c.5630T>A; p.(Leu1877*) | paternally inherited | This report |
| #13 | M-4 | a | epileptic seizures; low grade tumor | c.6709C>T; p.(Arg2237Ter) | NA | [24] |
| #14 | M-2 | a; b | none | c.6756+1G>T | de novo | [25] |
| #15 | F-33 | a; b; e; g | none | c.7096_7101del; p.(Asn2366_Phe2367del) | de novo | [26] |
| #16 | F-13 | a; b; e | none | c.7395-2A>G | maternally inherited | [27] |
| #17 | M-7 | a; d | none | Entire gene deletion | de novo | [28] |
[i] NA: not available.
National Institutes of Health criteria: a) Six or more café-au-lait spots over 5mm in greatest diameter in prepubertal individuals and over 15mm in postpubertal individuals. b) Two or more neurofibromas of any type or one or more plexiform neurofibromas. c) Freckling in the axillary or inguinal regions. d) Optic glioma. e) Two or more Lisch nodules. f) A distinctive osseous lesions such as sphenoid dysplasia or thinning of long bone cortex with or without pseudarthrosis. g) A first-degree relative with NF-1.
Figure 1
Broken right tibia of patient #8.
Figure 2
Distribution of mutations (black points) of patients (#) through the domains of neurofibromin. CSRD: cysteine-serine rich domain; TBD: tubulin binding domain; GRD: GAP-related domain; CTD: C-terminal domain; SBD: syndecan binding domain (domain structure is adapted from Ratner and Miller [7]).
Table 2
Clinical and demographic informations of the index patients that we did not define a pathogenic variant
| # | Sex-Age | NIH Criteria | Additional Findings |
|---|---|---|---|
| #18 | F-19 | a | afebrile convulsion; glial tumor |
| #19 | M-17 | a; b | none |
| #20 | M-6 | a; b | none |
| #21 | F-4 | a | none |
| #22 | M-2 | a | none |
| #23 | M-16 | a | T2 flair hyperintensive signals in the brain |
| #24 | M-15 | c | dysmorphic appearance of the face |
[i] National Institutes of Health criteria: a) Six or more café-au-lait spots over 5mm in greatest diameter in prepubertal individuals and over 15mm in postpubertal individuals. b) Two or more neurofibromas of any type or one or more plexiform neurofibromas. c) Freckling in the axillary or inguinal regions. d) Optic glioma. e) Two or more Lisch nodules. f) A distinctive osseous lesions such as sphenoid dysplasia or thinning of long bone cortex with or without pseudarthrosis. g) A first-degree relative with NF-1.
Table 3
Findings of familial patients.
| # | Sex-Age | NIH Criteria | Additional Findings | Pathogenic Variant (NM_000267) |
|---|---|---|---|---|
| #6 mother of #6 | F-8 F-38 | a; c; g a; c; g | none none | c 3230_3230de1IT; p (Ser1078Wiefe*3) |
| #8 father of #8 | F-7 mths M-33 | a; b; f; g a; b; g | none none | c.4802de1T; p.(Leu1601Cysis*2) |
| #12 father of #12 | F-2 M-35 | a a | afebrile convulsion none | c.5630T>A; p.(Leu1877*) |
| #15 son of #15 | F-33 M-7 | a; b; d; g a; g | ptosis in his left eye none | c.7096_7101de1; p.(Asn2366_Phe2367de1) |
| #16 mother of #16 | F-13 F-40 | a; b; d; g a; b; c; d; g | none glial tumor and medial malleolar breakage | C.7395-2A>G |
[i] National Institutes of Health criteria: a) Six or more café-au-lait spots over 5mm in greatest diameter in prepubertal individuals and over 15mm in postpubertal individuals. b) Two or more neurofibromas of any type or one or more plexiform neurofibromas. c) Freckling in the axillary or inguinal regions. d) Optic glioma. e) Two or more Lisch nodules. f) A distinctive osseous lesions such as sphenoid dysplasia or thinning of long bone cortex with or without pseudarthrosis. g) A first-degree relative with NF-1.