Variable expression of neurofibromatosis 1 in monozygotic twins

American Journal of Medical Genetics, Part A - Tập 155 Số 3 - Trang 478-485 - 2011
Margaret B. Rieley1, David A. Stevenson2, David Viskochil2, Brad T. Tinkle3, Lisa J. Martin3, Elizabeth K. Schorry3
1Eastern Maine Medical Center, Bangor, Maine, USA
2Division of Medical Genetics, University of Utah, Salt Lake City, Utah
3Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

Tóm tắt

AbstractNeurofibromatosis 1 (NF1) is a common autosomal dominant disorder with high penetrance but extreme variability of expression. Monozygotic (MZ) twins with NF1 who have phenotypic discordances are a useful tool in evaluating which traits are influenced by non‐hereditary influences such as second hit somatic events, environmental agents, epigenetic modification, or post‐zygotic mutations. We evaluated nine sets of MZ twins and one set of MZ triplets, ages 4–18 years, for NF1 features and calculated probandwise concordance (PC) for each feature. MZ twins were highly concordant in numbers of café‐au‐lait spots (PC = 0.89) and cutaneous neurofibromas. IQ scores were within 10 points for all twin pairs tested, and similar patterns of learning disabilities and speech disorders were observed. Twin pairs showed significant discordance for tumors, particularly plexiform neurofibromas (PC = 0.40) and malignant peripheral nerves sheath tumors (MPNST), as expected if post‐natal second‐hit events were contributing to these features. One set of twins was concordant for multiple, large paraspinal neurofibromas, suggesting that there may be more hereditary factors involved in production of paraspinal neurofibromas. Four sets were concordant for pectus deformities of the chest (PC = 0.80). Three sets of twins were discordant for scoliosis (PC = 0.40); an additional set was concordant for scoliosis but differed in presence of dystrophic features and need for surgery. Our data suggest there are additional non‐hereditary factors modifying the NF1 phenotype and causing discordancies between MZ twins. Future studies may focus on differences in epigenetic changes or somatic mosaicism which have been documented for other disease genes in MZ twins. © 2011 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1017/S0001566000005109

Bauer M, 1988, Variable expressivity of neurofibromatosis‐1 in identical twins, Neurofibromatosis, 1, 323

10.1016/j.ajhg.2007.12.011

10.1016/j.ymgme.2007.12.004

Carey JC, 1979, Penetrance and variability in neurofibromatosis: A genetic study of 60 families, Birth Defects Orig Artic Ser, 15, 271

10.1177/000992288202100408

10.1136/jmg.40.10.e109

10.1016/S0266-7681(05)80088-9

10.1111/j.1469-8749.1983.tb13774.x

10.5435/00124635-199907000-00002

Crowe FW, 1956, A clinical, pathological, and genetic study of multiple neurofibromatosis

10.1375/twin.10.3.486

Dresner E, 1949, Primary optic atrophy in von Recklinghausen's disease (multiple neurofibromatosis), Q J Med, 18, 93

Easton DF, 1993, An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): Evidence for modifying genes, Am J Hum Genet, 53, 305

10.1136/jmg.39.5.311

10.1073/pnas.0500398102

10.1002/(SICI)1096-8652(199608)52:4<281::AID-AJH7>3.0.CO;2-O

10.1002/(SICI)1096-8628(19970516)70:2<138::AID-AJMG7>3.0.CO;2-U

Huson SM, 1994, The Neurofibromatoses: A pathogenetic and clinical overview

10.1002/ajmg.a.33271

Kayes LM, 1994, Deletions spanning the neurofibromatosis 1 gene: Identification and phenotype of five patients, Am J Hum Genet, 54, 424

10.1177/000992289803700504

Koul RL, 2000, Dandy–Walker syndrome in association with neurofibromatosis in monozygotic twins, Saudi Med J, 21, 390

10.1007/s00198-004-1801-4

10.1007/s00198-005-1940-2

10.1016/S0161-6420(84)34217-8

10.1016/S0022-3476(89)80137-4

10.1002/ajmg.a.31303

MacGillivray I, 1975, Human multiple reproduction

10.1093/schbul/18.2.171

10.1002/ajmg.b.30316

10.1002/1096-8628(200022)97:2<119::AID-AJMG3>3.0.CO;2-3

10.1016/S0387-7604(88)80041-X

10.1177/08830738030180071101

10.1093/oxfordjournals.schbul.a006988

Riccardi VM, 1992, Neurofibromatosis: Phenotype, natural history, and pathogenesis

10.1093/hmg/ddp212

10.1111/j.1399-0004.2006.00576.x

10.1086/504441

10.1016/j.jpeds.2006.10.048

10.1136/jnnp.71.1.131

10.1086/510781

10.1007/s10048-009-0178-0

10.1002/ajmg.1320080205

10.1002/(SICI)1098-2272(1999)16:3<290::AID-GEPI5>3.0.CO;2-8

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American Journal of Medical Genetics, Part A

Tập 155 Số 3

478-485

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