Table 1. Review of manifestations in biallelic BRCA2 mutation cases.
| ID | Malformations | Sex | MDS/BMF | Cancer (age in years) | Allele 1 | Exon 1 | Allele 2 | Exon 2 | Outcome | Diagnosis presentation (in years) | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|
| ? | Microcephaly; esotropia; cerebellar hypoplasia; arachnoid cyst; abnormal radii and thumbs; clinodactyly; FTT; CLS | F | + | Bilateral Wilms' (1), myelodysplasia (2), medulloblastoma (2.5) | c.3264dupT p. (Gln1089Serfsa10) | 11 | c.8487+3A>G p.(Ile2778_Gln2829del) | 19i | Dead (2.5) of disease | Onset of bilateral Wilm's tumour+physical findings (1) | 25 |
| ? | Intestinal duplication cysts/mesenteric lymphangioma jejunum; FTT; microcephaly; CLS; ear anomalies; bilateral clinedactly | M | + | Neuroblastoma (1.3) aplasia ( 1.5) AML (1.7) | c.1813dupA, p. (lle605Asnfsa11) | 10 | c.631+2T>G p.(Gly173Serfsa19) | 7i | Dead (2) of disease | Physical findings (1.3) | 25 |
| ? | Holoprosencephaly; microcephaly; TEF; FTT; ear anomalies; hearing loss; pelvic kidneys; optic anomalies; polydactyly; CLS; congenital naevus | F | + | Differentiating neuronal neoplasm (1.7), MDS (2), AML (2.7) | c.2899_2900delCT, p.(Leu967Argfsa14) | 11 | c.7007G>A p.(Arg2336His) | 13 | Dead (2.7) of disease | Physical findings (0.2) | 25 |
| HSC62 | Abnormal thumb | M | NA | None (30) | c.8488-1G>A r.8488_8491del p.(Trp2830_Lys2833del) | 19i | c.8488-1G>A r.8488_8491del p.(Trp2830_Lys2833del) | 19i | Alive (30) | NA | 21 |
| EUFA423 | Pigmented, abnormal thumb | F | NA | Brain (3) | c.7464_7465insTA p. (Asp2489a) | 15 | c.9672dupA p. (Tyr3225Ilefsa30) | 27 | Alive (3) | NA | 21 |
| EUFA579 | Pigmented, abnormal thumb | F | NA | AML (NA) | c.7007G>A p.(Arg2336His) | 13 | c.5609_5610delTCinsAG p. (Phe1870a) | 11 | Alive (NA) | NA | 21 |
| AP37P | Short, pigmented, CLS, abnormal thumb, Sprengel, midface hypoplasia | M | + | AML M2 (2) | c.8187G>T p. (Lys2729Asn) | 18 | c.8504C>A p.(Ser2835a) | 20 | Dead (3.9) of disease | Physical findings (2) | 24 |
| 1A | Short CLS, pigmented, abnormal thumbs and radii, microcephaly, imperforate anus, epicanthal folds, micropenis, undescended testes, dislocated hips, hydronephrosis, abnormal; hearing (VATERa) | M | NA | Brain–medulloblastoma or astrocytoma (4.9) | c.5946delT p. (Ser1982Argfsa22) | 11 | c.9207T>A p.(Cys3069a) | 24 | Dead (4.9) of disease | Physical findings (1.4) | 27 |
| 1B | Short, abnormal thumbs, microcephaly, imperforate anus with rectovaginal fistula, slanted eyes, anomalous kidneys, small ear, hip dysplasia (VATERa) | M | NA | Brain–astrocytoma (2) | c.5946delT p. (Ser1982Argfsa22) | 11 | c.9207T>A p.(Cys3069a) | 24 | Dead (2) of disease | Physical findings (NA) | 27 |
| 2 | No exam reported | F | NA | Brain–medulloblastoma (4.5) | c.5946delT p. (Ser1982Argfsa22) | 11 | c.658_659delGT p.(Val220Ilefsa4) | 8 | Alive (4.5) | NA | 27 |
| 3 | No exam reported | F | NA | Brain–medulloblastoma (2.5) | c.5073dupA p.(Trp1692Metfsa3) | 11 | c.7669T >C p.(Ile2490Thr) | 15 | Alive (2.5) | NA | 27 |
| 4 | No exam reported | F | NA | Brain–medulloblastoma (3.5) | c.3922G>T p.(Glu1308a) | 11 | c.9196C>T p.(Gln3066a) | 24 | Alive (3.5) | NA | 27 |
| 772/1 | CLS, microcephaly, cardiac (patent ductus arteriosus) | M | − | Brain–medulloblastoma (2.3) | c.658_659delGT p. (Val220Ilefsa4) | 8 | c.8219T>A p.(Leu2740a) | 18 | Dead (2.5) of toxicity | Toxicity to chemotherapy (2.5) | 20 |
| 772/2 | CLS, abnormal facies, Epicanthus, clinodactily | M | − | Wilms' (1.3), Brain–medulloblastoma (4.3) | c.658_659delGT p. (Val220Ilefsa4) | 8 | c.8219T>A p.(Leu2740a) | 18 | Dead (4.5) of toxicity | Onset of Wilm's tumour+familial history (1.3) | 20 |
| K2S1 | Short, microcephaly | M | − | Wilms' (0.5), AML (2) | c.4648G>T p.(Glu1550a) | 11 | c.7529T>C p.(Leu2510Pro) | 15 | Dead (2) of toxicity | Toxicity to chemotherapy (2) | 20 |
| K2S2 | Short, pigmented macules, bifid thumb, elfin facies, small palpebral fissures | F | T-ALL (5) | c.4648G>T p.(Glu1550a) | 11 | c.7529T>C p.(Leu2510Pro) | 15 | Dead (5) of toxicity | Familial history (at birth) | 20 | |
| 129/1 | Short, CLS, FTT microcephaly, imperforate anus | NA | NA | AML (2.2) | c. 631+2T>G p.(Gly173Serfsa19) | 7i | c. 631+2T>G p.(Gly173Serfsa19) | 7i | Dead (5.2) | Physical findings (NA) | 20 |
| 357/1 | Short, thumb, imperforate anus, FTT | NA | NA | AML (1.9) | c.7878G>C p. p.(Trp2626Cys) | 17 | c.1813dupA p.(Ile605Asnfsa11) | 10 | Dead (2.8) | Physical findings (NA) | 22 |
| 632/1 | Short, CLS, dysplastic hips, pelvic kidney | F | NA | AML (3) | c. 631+1G>A p.(?) | 7i | c.5682C>G p.(Tyr1894a) | 11 | Dead (5) | Physical findings (NA) | 22 |
| 632/2 | Short, imperforate anus, hypoplastic thumb | F | NA | AML (1.8) | c. 631+1G>A p.(?) | 7i | c.5682C>G p.(Tyr1894a) | 11 | Alive (2.4) | Physical findings (NA) | 22 |
| 800/1 | Short, CLS, FTT, microcephaly, micropenis | M | NA | AML (0.9) | c. 631+2T>G p.(Gly173Serfsa19) | 7i | c.4936_4939delGAAA p. (Glu1646Glnfsa23) | 11 | Dead (1.7) of disease | Physical findings (NA) | 22 |
| 800/2 | Short, CLS, FTT, microcephaly | M | + | Wilms' (0.8) | c. 631+2T>G p.(Gly173Serfsa19) | 7i | c.4936_4939delGAAA p.(Glu1646Glnfsa23) | 11 | Alive (0.8) | Physical findings (NA) | 22 |
| 900/1 | Short, CLS, FTT | M | − | ALL (5.2) | c.2588dupA p. (Asn863Lysfsa18) | 11 | c.1114C>A p.(Asn372His) | 10 | Alive (6.6) | Physical findings (NA) | 22 |
| RB | Short, pigmented, CLS, microcephaly, cryptorchidism | M | NA | Wilms' (3.5), Brain–glioblastoma multiforme (9) | c.658_659delGT p.(Val220Ilefsa4) | 8 | c.5645C>A p.(Ser1882a) | 11 | Dead (10.1) Of disease | NA | 28 |
| CB | Pigmented, CLS | M | NA | Wilms' (0.6), Brain–medulloblastoma (6), B-ALL (10) | c.658_659delGT p.(Val220Ilefsa4) | 8 | c.5645C>A p.(Ser1882a) | 11 | Dead (12) Of disease | NA | 28 |
| SB1690CB | Hypermobile thumb,FTT, microcephaly, imperforate anus, deaf, renal dysplasia, midfacial hypoplasia (VATERa) | M | + | MSD (1.2) AML (2.1) | c. 631+2T>G p.(Gly173Serfsa19) | 7i | c.3599_3600delGT p.(Cys1200a) | 11 | Dead (2.3) Of disease | Physical finding (1.2) | 25 |
| PT2 | Short, pigmented, CLS, adducted thumbs, microcephaly, sacral hemivertebra, ventricular septal defect, pelvic kidney, oesophageal atresia, micrognathia, CNS gyrations, congenital cataract (VATERa) | F | + | Wilms' (1), neuroblastoma (1.1), Brain–posterior fossa (1.4) | c.1311_1314delAGAT p.(Lys437Asnfsa22) | 10 | c.1311_1314delAGAT p.(Lys437Asnfsa22) | 10 | Dead (1.4) of disease | Physical finding (0.1) | 19 |
| NCI 1 | Short, CLS, microcephaly, facial dysmorphia, abnormal thumbs, anterior anus, cloudy corneas, ectopic kidneys, delayed development, hydrocephaly (VATERa) | F | NA | Brain–medulloblastoma (3.1) | c.5946delT p.(Ser1982Argfsa22) | 11 | c.9196C>T p.(Gln3066a) | 24 | Alive (3.1) | Physical findings (VACTER) (1.7) | 12 |
| ? | No physical abnormality | M | NA | High grade neuroepithelial tumour (1.3) | c.5946delT p.(Ser1982Argfsa22) | 11 | c.658_659delGT p.(Val220Ilefsa4) | 8 | Dead (1.6) of toxicity | Familial history (Retrospectively) | 23 |
| 12 | No physical abnormality | M | + | Medulloblastoma (1.7) | c.5946delT p.(Ser1982Argfsa22) | 11 | c.658_659delGT p.(Val220Ilefsa4) | 8 | Alive (2) | Toxicity to therapy+age of cancer (2) | 23 |
| ? | CLS | F | − | Lymphoma (31) Colon_Adenocarcinoma (31) | c.7802A>G p.[Tyr2601Cys, Tyr2601Trpfsa46] r.[7802a>g,7802_7805del] | 16 | c.1845_1846delCT p.(Asn615Lysfsa6) | 10 | Alive (34) | Familial history (34) | Current report |
| ? | Microcephaly, CLS, exophthalmia | F | − | Breast cancer (29) Colon_Adenocarcinoma (27) | c.7802A>G p.[Tyr2601Cys, Tyr2601Trpfsa46] r.[7802a>g,7802_7805del] | 16 | c.1845_1846delCT p.(Asn615Lysfsa6) | 10 | Alive (31) | Breast Cancer (30) | Current report |
| ? | Microcephaly, short stature | F | + | AML (5) | c.7802A>G p.[Tyr2601Cys, Tyr2601Trpfsa46]r.[7802a>g,7802_7805del] | 16 | c.1845_1846delCT p.(Asn615Lysfsa6) | 10 | Dead (5) of toxicity | Familial history (retrospectively) | Current report |
Abbreviations: i, intron; NA, not available; F, female; M, male; ALL, acute lymphoblastic leukaemia; AML, acute myelogenous leukaemia; MDS, myelodysplasia; BMF, bone marrow failure; CLS, café-au-lait spots; FTT, failure to thrive; CNS, central nervous system; TEF, tracheoesophageal fistula.
a
VATER association includes vertebral anomalies, anal atresia, tracheoesophageal fistula with esophageal atresia, and abnormal radi.