Germline Mosaicism in Neurofibromatosis Type 1 Due to a Paternally Derived Multi-Exon Deletion

被引：22

作者：

Bottillo, Irene ^{[1
]}

Torrente, Isabella ^{[1
]}

Lanari, Valentina ^{[1
]}

Pinna, Valentina ^{[1
]}

Giustini, Sandra ^{[2
]}

Divona, Luigina ^{[2
]}

De Luca, Alessandro ^{[1
]}

Dallapiccola, Bruno ^{[3
]}

机构：

[1] Casa Sollievo Sofferenza Hosp, IRCCS, San Giovanni Rotondo, Italy

[2] Univ Roma La Sapienza, Dept Dermatol Venereol & Plast & Reconstruct Surg, Rome, Italy

[3] Bambino Gesu Children Hosp, IRCCS, Rome, Italy

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART A | 2010年 / 152A卷 / 06期

关键词：

neurofibromatosis type 1 (NF1); germline mosaicism; real time PCR; NF1 GENE DELETIONS; AU-LAIT SPOTS; SEGMENTAL NEUROFIBROMATOSIS; SOMATIC MOSAICISM; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; BENIGN NEUROFIBROMAS; LINE MOSAICISM; SCHWANN-CELLS; MUTATION; FISH;

D O I：

10.1002/ajmg.a.33386

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We report on the clinical and molecular features of a family in which neurofibromatosis type 1 (NF1) occurred in two of three siblings born to unaffected parents and in one granddaughter. Linkage analysis showed that the two affected siblings and the daughter of one of them shared the same paternal allele, whereas they had inherited different maternal alleles. We detected a disease-causing deletion (c.4773-3622-?_5749+?del) encompassing three NF1 gene exons in affected individuals. This mutation occurred on the paternally derived allele, arguing for a germline mosaicism in the probands' father. Real-time PCR showed that the mutation was present in about 10-17% of the paternal sperms. Current results confirm that germline mosaicism can explain the recurrence of NF1 in offspring of unaffected parents. (C) 2010 Wiley-Liss, Inc.

引用

页码：1467 / 1473

页数：7

共 59 条

[1]

Ainsworth PJ, 1997, HUM MUTAT, V9, P452, DOI 10.1002/(SICI)1098-1004(1997)9:5<452::AID-HUMU12>3.0.CO

[2]

2-1

[3] Hereditary retinoblastoma transmitted by maternal germline mosaicism [J].

Barbosa, Raquel H. ;

Vargas, Fernando R. ;

Aguiar, Fernanda C. C. ;

Ferman, Sima ;

Lucena, Evandro ;

Bonvicino, Cibele R. ;

Seuanez, Hector N. .

PEDIATRIC BLOOD & CANCER, 2008, 51 (05) :598-602

[4] ABERRANT REGULATION OF RAS PROTEINS IN MALIGNANT-TUMOR CELLS FROM TYPE-1 NEUROFIBROMATOSIS PATIENTS [J].

BASU, TN ;

GUTMANN, DH ;

FLETCHER, JA ;

GLOVER, TW ;

COLLINS, FS ;

DOWNWARD, J .

NATURE, 1992, 356 (6371) :713-715

[5] Germline and somatic NF1 mutations in sporadic and NF1-associated malignant peripheral nerve sheath tumours [J].

Bottillo, Irene ;

Ahiquist, Terje ;

Brekke, Helge ;

Danielsen, Stine A. ;

van den Berg, Eva ;

Mertens, Fredrik ;

Lothe, Ragnhild A. ;

Dallapiccola, Bruno .

JOURNAL OF PATHOLOGY, 2009, 217 (05) :693-701

[6] Glomus Tumors in Neurofibromatosis Type 1: Genetic, Functional, and Clinical Evidence of a Novel Association [J].

Brems, Hilde ;

Park, Caroline ;

Maertens, Ophelia ;

Pemov, Alexander ;

Messia, Ludwine ;

Upadhyaya, Meena ;

Claes, Kathleen ;

Beert, Eline ;

Peeters, Kristel ;

Mautner, Victor ;

Sloan, Jennifer L. ;

Yao, Lawrence ;

Lee, Chyi-Chia Richard ;

Sciot, Raf ;

De Smet, Luc ;

Legius, Eric ;

Stewart, Douglas R. .

CANCER RESEARCH, 2009, 69 (18) :7393-7401

[7]

CAREY JC, 1986, ANN NY ACAD SCI, V486, P45, DOI DOI 10.1111/J.1749-6632.1986.TB48061.X

[8]

Castori M, 2008, EUR J DERMATOL, V18, P22

[9] A MAJOR SEGMENT OF THE NEUROFIBROMATOSIS TYPE-1 GENE - CDNA SEQUENCE, GENOMIC STRUCTURE, AND POINT MUTATIONS [J].

CAWTHON, RM ;

WEISS, R ;

XU, GF ;

VISKOCHIL, D ;

CULVER, M ;

STEVENS, J ;

ROBERTSON, M ;

DUNN, D ;

GESTELAND, R ;

OCONNELL, P ;

WHITE, R .

CELL, 1990, 62 (01) :193-201

[10]

Colman SD, 1996, AM J HUM GENET, V58, P484

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