Genotypes and phenotypes of FA patients with BRCA2 mutations
. | . | Breaks/cell . | . | . | . | . | BRCA2 mutations, exon . | . | . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Kindred . | IFAR no. . | Spon . | DEB . | Clinical manifestations . | Hematologic manifestations . | Survival at last follow-up, mo . | Paternal . | Maternal . | Family cancer history, relation and age . | ||
| 1* | 129/1 | 0.84 | 8.0 | IUGR, imperforate anus, café au lait, microcephaly, FTT | AML at 26 mo, chemotherapy refractory | 36 | IVS7 + 2T>G, IVS7 | IVS7 + 2T>G, IVS7 | Breast: PGM 40 y, MA 45 y; Pancreatic: MU 51 y | ||
| 2 | 357/1 | 0.12 | 3.7 | IUGR, imperforate anus, hypoplastic thumb, FTT | AML at 23 mo, chemotherapy refractory | 9 | W2626C† 8106G>C, 17 | 2041 insA, 10 | Breast: MGM 46 y, MGGM 46 y, MGGA 45 y; Prostate: MGF 48 y; Bladder: MGGF 51 y | ||
| 3 | 632/1 | 1.0 | 13.9 | IUGR, short stature, café au lait, bilateral hip dysplasia | AML at 36 mo, chemotherapy refractory | 48 | IVS7 + 1G>A, IVS7 | Y1894X 5910C>G, 11 | Breast: M 38 y, MGF 60 y, PGM 48 y | ||
| 632/2 | — | 7.7 | IUGR, short stature | AML at 21 mo, chemotherapy refractory | 29+, alive/well | ||||||
| 4 | 800/1 | 0.40 | 14.0 | IUGR, microcephaly, FTT, micropenis, café au lait | AML at 11 mo, chemotherapy refractory | 26 | IVS7+2T>G, IVS7 | 5164del4, 11 | Brain tumor: MGGF 50 y | ||
| 800/2 | 1.1 | 11.1 | IUGR, microcephaly, café au lait, FTT | Neutropenia at 5 mo, Wilms tumor at 9 mo | 9+, alive/well | ||||||
| 5 | 900/1 | 6.6‡ | 25.9‡ | IUGR, FTT, café au lait | T-cell ALL at 62 mo, complete remission after chemotherapy | 90+, alive/well | 2816insA, 11 | Abnormal RNA transcript§ | Breast: MGM 29 y | ||
. | . | Breaks/cell . | . | . | . | . | BRCA2 mutations, exon . | . | . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Kindred . | IFAR no. . | Spon . | DEB . | Clinical manifestations . | Hematologic manifestations . | Survival at last follow-up, mo . | Paternal . | Maternal . | Family cancer history, relation and age . | ||
| 1* | 129/1 | 0.84 | 8.0 | IUGR, imperforate anus, café au lait, microcephaly, FTT | AML at 26 mo, chemotherapy refractory | 36 | IVS7 + 2T>G, IVS7 | IVS7 + 2T>G, IVS7 | Breast: PGM 40 y, MA 45 y; Pancreatic: MU 51 y | ||
| 2 | 357/1 | 0.12 | 3.7 | IUGR, imperforate anus, hypoplastic thumb, FTT | AML at 23 mo, chemotherapy refractory | 9 | W2626C† 8106G>C, 17 | 2041 insA, 10 | Breast: MGM 46 y, MGGM 46 y, MGGA 45 y; Prostate: MGF 48 y; Bladder: MGGF 51 y | ||
| 3 | 632/1 | 1.0 | 13.9 | IUGR, short stature, café au lait, bilateral hip dysplasia | AML at 36 mo, chemotherapy refractory | 48 | IVS7 + 1G>A, IVS7 | Y1894X 5910C>G, 11 | Breast: M 38 y, MGF 60 y, PGM 48 y | ||
| 632/2 | — | 7.7 | IUGR, short stature | AML at 21 mo, chemotherapy refractory | 29+, alive/well | ||||||
| 4 | 800/1 | 0.40 | 14.0 | IUGR, microcephaly, FTT, micropenis, café au lait | AML at 11 mo, chemotherapy refractory | 26 | IVS7+2T>G, IVS7 | 5164del4, 11 | Brain tumor: MGGF 50 y | ||
| 800/2 | 1.1 | 11.1 | IUGR, microcephaly, café au lait, FTT | Neutropenia at 5 mo, Wilms tumor at 9 mo | 9+, alive/well | ||||||
| 5 | 900/1 | 6.6‡ | 25.9‡ | IUGR, FTT, café au lait | T-cell ALL at 62 mo, complete remission after chemotherapy | 90+, alive/well | 2816insA, 11 | Abnormal RNA transcript§ | Breast: MGM 29 y | ||
Spon indicates mean number of spontaneous breaks per cells; DEB, mean number of DEB induced (0.1 μg/mL, DEB) per cell; FTT, failure to thrive; PGM, paternal grandmother; MA, maternal aunt; MU, maternal uncle; MGM, maternal grandmother; MGGM, maternal great grandmother; MGGA, maternal great grand aunt; MGF, maternal grandfather; MGGF, maternal great grandfather; M, mother; and —, not done.
Parents are second cousins, and patient IFAR 129/1 is homozygous by descent for BRCA2*IVS7+2T>G.
Classified as a variant of unknown significance in the BIC database.
Chromosomal breakage evaluation performed on cells after induction chemotherapy.
DNA analysis revealed an unidentified mutation causing aberrant splicing upstream of exon 3.