Microduplication of 3p25.2 encompassing RAF1 associated with congenital heart disease suggestive of Noonan syndrome

Authors

  • Cheng Luo,

    1. Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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  • Yi-Feng Yang,

    1. Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
    2. Clinical Center for Gene Diagnosis and Therapy of State Key Laboratory of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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  • Bang-Liang Yin,

    1. Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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  • Jin-Lan Chen,

    1. Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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  • Can Huang,

    1. Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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  • Wei-Zhi Zhang,

    1. Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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  • Jian Wang,

    1. Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
    2. Clinical Center for Gene Diagnosis and Therapy of State Key Laboratory of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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  • Hong Zhang,

    1. Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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  • Jin-Fu Yang,

    1. Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
    2. Clinical Center for Gene Diagnosis and Therapy of State Key Laboratory of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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  • Zhi-Ping Tan

    Corresponding author
    1. Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
    2. Clinical Center for Gene Diagnosis and Therapy of State Key Laboratory of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
    • Department of Cardiothoracic Surgery, The 2nd Xiangya Hospital of Central South University, 139# Renmin Road, Changsha, Hunan 410011, China.
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  • The authors declare no conflict of interest.

  • How to Cite this Article: Luo C, Yang Y-F, Yin B-L, Chen J-L, Huang C, Zhang W-Z, Wang J, Zhang H, Yang J-F, Tan Z-P. 2012. Microduplication of 3p25.2 encompassing RAF1 associated with congenital heart disease suggestive of Noonan syndrome. Am J Med Genet Part A. 158A:1918–1923.

Abstract

Noonan syndrome (NS) is a clinically variable and genetically heterogeneous disorder with congenital heart defects (CHD), short stature, and craniofacial dysmorphisms. Gain-of-function mutations in RAF1 can cause NS and the highly related NS with multiple lentigines (previously known as LEOPARD syndrome). Here we report on a 15-year-old male with NS phenotype: short stature, heart defects, low posterior hairline, facial malformations, malformed left ear with sensorineural hearing loss, widely spaced nipples, and unilateral upper limb anomaly. Using high-resolution SNP array technology, we identified in this patient a 0.25 Mb microduplication at 3p25.2 in which RAF1 is located. Sequence analysis did not identify mutations in genes associated with Holt-Oram syndrome. These findings suggest that duplications of genomic regions encompassing RAF1 could cause NS and are consistent with the notion that rare copy number variations encompassing causative genes may underlie a small percentage of patients with syndromic CHD like NS. © 2012 Wiley Periodicals, Inc.

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