World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 7, Number 5-6, December 2016, pages 104-108

Positive Germline Selection in Pedigrees With Multiple Endocrine Neoplasia Type 2 Carrying V804M Mutation in the RET Gene

Figure 2. Pedigree of 107 members of a multigenerational Italian-American family with autosomal dominant transmission of the V804M RET mutation causing MEN2A in the affected individuals. Solid circles and squares indicate individuals positive for the V804M RET mutation.

**Table 1.** Frequency of Inheritance and Germline Transmission of V804M RET Mutation in Three Multigenerational Families
Generation	Total members	Total members tested from positive parent	V804M frequency based on the patients at risk	Frequency of V804M germline inheritance based on the patients at risk
Data showing the observed and expected frequency of inheritance of V804M RET mutation in each generation and the observed and expected frequency of transmission to the progeny of V804M RET mutation from a positive father (paternal) compared to a positive mother (maternal) in all three families. *One pair of monozygotic twins considered as one individual for the analysis. ^†Only individuals who were tested for the V804M mutation were included in the analysis. ^@Total tested positive plus positives Inferred from positive children.
Family 1
Generation II	3	2^@	0	2/3	1.5/3	-	-	-	-	-	-
Generation III	5	4	0	4/5	2.5/5	3	2	1.5	2	2	1
Generation IV	9*	7	2*	7/9*	4.5/9*	6	5	3	3*	2	1.5
All	17*	13	2	13/15^†	7.5/15^†	9	7	4.5	5*	4	2.5
Family 2
Generation II	6	4^@	0	4/6	3/6	-	-	-	-	-	-
Generation III	12	7	5	7/12	6/12	-	-	-	12	7	6
Generation IV	13	9	4	9/13	6.5/13	-	-	-	13	9	6.5
All	31	20	9	20/29^†	14.5/29^†	-	-	-	25	16	12.5
Family 3
Generation I	10	8^@	1	8/9	4.5/9	-	-	-		-	-
Generation II	27	17	5	17/22	11/22	9^†	7	4.5	13^†	10	6.5
Generation III	66	15	7	15/22	11/22	2^†	1	1	20^†	14	10^†
Generation IV	4	0	0	-	-	-	-	-	-	-	-
All	107	40	13	40/53^† P < 0.001	26.6/53^†	11^†	8 P = 0.132	5.5	33^†	24 P = 0.005	16.5^†
Total	73	24	73/97^† P < 0.001	48.5/97	20^†	15 P = 0.012	10	63^†	44 P = 0.001	31.5

Table 1. Frequency of Inheritance and Germline Transmission of V804M RET Mutation in Three Multigenerational Families

Generation

Total members

Total members tested from positive parent

V804M frequency based on the patients at risk

Frequency of V804M germline inheritance based on the patients at risk

Positive

Negative

Observed

Expected

Paternal inheritance

Maternal inheritance

Total

Positive

Expected

Total

Positive

Expected

Data showing the observed and expected frequency of inheritance of V804M RET mutation in each generation and the observed and expected frequency of transmission to the progeny of V804M RET mutation from a positive father (paternal) compared to a positive mother (maternal) in all three families. *One pair of monozygotic twins considered as one individual for the analysis. ^†Only individuals who were tested for the V804M mutation were included in the analysis. ^@Total tested positive plus positives Inferred from positive children.

Family 1

Generation II

2^@

2/3

1.5/3

Generation III

4/5

2.5/5

1.5

Generation IV

7/9*

4.5/9*

1.5

All

17*

13/15^†

7.5/15^†

4.5

2.5

Family 2

Generation II

4^@

4/6

3/6

Generation III

7/12

6/12

Generation IV

9/13

6.5/13

6.5

All

20/29^†

14.5/29^†

12.5

Family 3

Generation I

8^@

8/9

4.5/9

Generation II

17/22

11/22

9^†

4.5

13^†

6.5

Generation III

15/22

11/22

2^†

20^†

10^†

Generation IV

All

107

40/53^†
P < 0.001

26.6/53^†

11^†

8
P = 0.132

5.5

33^†

24
P = 0.005

16.5^†

Total

73/97^†
P < 0.001

48.5/97

20^†

15
P = 0.012

63^†

44
P = 0.001

31.5

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 7, Number 5-6, December 2016, pages 104-108

Positive Germline Selection in Pedigrees With Multiple Endocrine Neoplasia Type 2 Carrying V804M Mutation in the RET Gene

**Table 1.** Frequency of Inheritance and Germline Transmission of V804M RET Mutation in Three Multigenerational Families
Generation	Total members	Total members tested from positive parent	V804M frequency based on the patients at risk	Frequency of V804M germline inheritance based on the patients at risk
Data showing the observed and expected frequency of inheritance of V804M RET mutation in each generation and the observed and expected frequency of transmission to the progeny of V804M RET mutation from a positive father (paternal) compared to a positive mother (maternal) in all three families. *One pair of monozygotic twins considered as one individual for the analysis. ^†Only individuals who were tested for the V804M mutation were included in the analysis. ^@Total tested positive plus positives Inferred from positive children.
Family 1
Generation II	3	2^@	0	2/3	1.5/3	-	-	-	-	-	-
Generation III	5	4	0	4/5	2.5/5	3	2	1.5	2	2	1
Generation IV	9*	7	2*	7/9*	4.5/9*	6	5	3	3*	2	1.5
All	17*	13	2	13/15^†	7.5/15^†	9	7	4.5	5*	4	2.5
Family 2
Generation II	6	4^@	0	4/6	3/6	-	-	-	-	-	-
Generation III	12	7	5	7/12	6/12	-	-	-	12	7	6
Generation IV	13	9	4	9/13	6.5/13	-	-	-	13	9	6.5
All	31	20	9	20/29^†	14.5/29^†	-	-	-	25	16	12.5
Family 3
Generation I	10	8^@	1	8/9	4.5/9	-	-	-		-	-
Generation II	27	17	5	17/22	11/22	9^†	7	4.5	13^†	10	6.5
Generation III	66	15	7	15/22	11/22	2^†	1	1	20^†	14	10^†
Generation IV	4	0	0	-	-	-	-	-	-	-	-
All	107	40	13	40/53^† P < 0.001	26.6/53^†	11^†	8 P = 0.132	5.5	33^†	24 P = 0.005	16.5^†
Total	73	24	73/97^† P < 0.001	48.5/97	20^†	15 P = 0.012	10	63^†	44 P = 0.001	31.5

Table 1. Frequency of Inheritance and Germline Transmission of V804M RET Mutation in Three Multigenerational Families

Generation

Total members

Total members tested from positive parent

V804M frequency based on the patients at risk

Frequency of V804M germline inheritance based on the patients at risk

Positive

Negative

Observed

Expected

Paternal inheritance

Maternal inheritance

Total

Positive

Expected

Total

Positive

Expected

Family 1

Generation II

2^@

2/3

1.5/3

Generation III

4/5

2.5/5

1.5

Generation IV

7/9*

4.5/9*

1.5

All

17*

13/15^†

7.5/15^†

4.5

2.5

Family 2

Generation II

4^@

4/6

3/6

Generation III

7/12

6/12

Generation IV

9/13

6.5/13

6.5

All

20/29^†

14.5/29^†

12.5

Family 3

Generation I

8^@

8/9

4.5/9

Generation II

17/22

11/22

9^†

4.5

13^†

6.5

Generation III

15/22

11/22

2^†

20^†

10^†

Generation IV

All

107

40/53^†
P < 0.001

26.6/53^†

11^†

8
P = 0.132

5.5

33^†

24
P = 0.005

16.5^†

Total

73/97^†
P < 0.001

48.5/97

20^†

15
P = 0.012

63^†

44
P = 0.001

31.5