Table 1. CNC kindreds/probands with PRKAR1A mutations: Genotypes and clinical manifestations of disease in family members.
| Family | Country | PRKAR1A mutation | Mutation consequence | Cardiac myxoma | Skin myxoma | Lent. | Endocr. | Other tumors | CHD | Other phenotypes |
|---|---|---|---|---|---|---|---|---|---|---|
| YA | USA | Del(G)710 | Fs-PSC | + | + | + | + | Schwannoma, TA, breast FA | ||
| YB | USA | Del(TC)845-846 | Fs-PSC | + | + | + | + | Breast FA, TA | ||
| YC11 | Ireland | Del(TG)139-140 | Fs-PSC | - | + | + | - | Breast FA, gastric carcinoma | Pilonidal sinus | |
| YD | USA | C584T | Nonsense | + | + | + | + | |||
| YF | USA | Del(TG)576-577 | Fs-PSC | + | - | + | ||||
| YJ | Belgium | Ins(GG)675 | Fs-PSC | + | - | + | + | Sertoli, schwannoma | ||
| YN | Ireland | Del(AA)745-746 | Fs-PSC | + | + | + | + | Sertoli, schwannoma, breast FA, pituitary adenoma | ||
| YO | Switzerland | C376T | Nonsense | + | - | - | + | |||
| YP | Switzerland | Del(TG)576-577 | Fs-PSC | + | + | + | + | Breast FA, TA | ||
| YR | USA | Ins(C)632 | Fs-PSC | + | - | + | - | ASD | ||
| YT | USA | Del(T)706 | Fs-PSC | + | + | + | - | |||
| YW | Germany | Del(TG)576-577 | Fs-PSC | + | + | - | + | Breast FA | PFO | Sudden death |
| YX | Japan | Del(GGTCTA)-1G-642 | Splicing/in-frame Δ-Exon 7; deletion* | + | - | + | - | |||
| YY | USA | C769T | Nonsense | + | - | + | - | Breast FA | ||
| YZ | USA | C769T | Nonsense | - | + | + | + | Schwannoma | ||
| YDD | France | IVS4 + 1G > A | Splicing/Fs-PSC | + | - | + | - | |||
| YEE | USA | IVS5 + 1G ins(T) | Splicing/Fs-PSC | + | - | + | - | Trichofolliculoma | ||
| YFF | Hong Kong | IVS6 - 17T > A | Splicing/Fs-PSC | - | - | + | + | |||
| YII | Australia | Ins(A)710 | Fs-PSC | + | - | + | - | Sertoli | ||
| YMM | Austria | C769T | Nonsense | + | + | - | - | Sertoli, breast FA | ||
| YNN | Japan | C769T | Nonsense | + | - | - | - | |||
| YPP | England | C307T | Missense: R74C*,† | + | - | + | - | Breast myxofibroma, TA | PS | Deafness |
| YSS | USA | Del(TG)576-577 | Fs-PSC | + | - | - | - | |||
| YTT | Japan | C997T | Nonsense* | + | - | - | + | TA, colon polyps | ||
| YUU | Brazil | Ins(T)891 | Fs-PSC | + | - | - | + | Breast FA | ||
| YZZ | Finland | Del(TG)576-577 | Fs-PSC | + | + | + | - | Tibia & femur fibromas | ||
| CCE | Canada | Del(A)1038 | Fs-PSC* | + | - | + | - | Sertoli, breast FA | ||
| CCN | USA | IVS4 - 1 A > G | Splicing/Fs-PSC | + | - | + | + | Adrenal adenomas, sertoli | Blaschko's lines | |
| CCR | England | IVS5 + 3 A > C | Splicing/Fs-PSC | - | - | + | - | Myxoid neurofibroma | ||
| CCS | USA | IVS3 + 1 G > C | Splicing/Fs-PSC | - | - | + | - | Schwannoma, sertoli | ||
| CCV | USA | Del(GATT)615-618, Ins(TATGATCAATC)615 | Fs-PSC | + | - | + | - | Nasal hamartoma | Ankylosing spondylitis | |
| SY13 | Turkey | IVS8 + 5 G > C | Splicing/Fs-PSC | + | - | + | + | TOF | ||
| SY21 | USA | Del(TG)576-577 | Fs-PSC | + | - | + | + |
Fs-PSC, frameshift mutation with consequent PSC; Splicing, mutation that alters PRKAR1A mRNA splicing; TA, thyroid adenoma; breast FA, breast fibroadenoma; ASD, atrial septal defect; PFO, patent foramen ovale; PS, pulmonic stenosis; TOF, Tetralogy of Fallot; CHD, congenital heart defect; Lent., lentiginosis; Endocr., endocrinopathy.
*
PRKAR1A mutant mRNA expressed and not subject to NMD.
†
Mutant R1α protein expressed.