LETTER TO JMG

Clinical and molecular analysis of Mowat-Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22–q24.1

N Ishihara^1,2, K Yamada¹, Y Yamada¹, K Miura³, J Kato⁴, N Kuwabara⁵, Y Hara⁶, Y Kobayashi⁷, K Hoshino⁸, Y Nomura⁸, M Mimaki⁹, K Ohya¹⁰, M Matsushima¹¹, H Nitta¹², K Tanaka¹³, M Segawa⁸, T Ohki³, T Ezoe¹⁵, T Kumagai³, A Onuma⁷, T Kuroda¹⁶, M Yoneda¹⁷, T Yamanaka³, M Saeki¹⁶, M Segawa¹⁴, T Saji¹⁴, M Nagaya⁴, N Wakamatsu¹

¹ Department of Genetics, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
² Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
³ Department of Pediatric Neurology, Central Hospital, Aichi Human Service Center, Kasugai, Aichi, Japan
⁴ Department of Pediatric Surgery, Central Hospital, Aichi Human Service Center, Kasugai, Aichi, Japan
⁵ Department of Pediatric Cardiology, Gifu Prefectural Hospital, Gifu, Japan
⁶ Department of Pediatrics, Obama Public Hospital, Obama, Fukui, Japan
⁷ Division of Pediatric Neurology, Takutoh Rehabilitation Center for Children, Sendai, Miyagi, Japan
⁸ Segawa Neurological Clinic for Children, Tokyo, Japan
⁹ Department of Pediatrics, Chigasaki Municipal Hospital, Chigasaki, Kanagawa, Japan
¹⁰ Department of Pediatrics, Aomori Central Hospital, Aomori, Japan
¹¹ Department of Pediatric Cardiology, Social Insurance Chukyo Hospital, Nagoya, Japan
¹² Department of Pediatrics, Hamagumi Medical and Educational Center for Handicapped Children, Niigata, Japan
¹³ Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
¹⁴ Division of Pediatric Cardiology, Department of 1st Pediatrics, Toho University, Tokyo, Japan
¹⁵ Department of Pediatric Neurology, Tokyo Metropolitan Higashiyamato Medical Center for the Handicapped, Higashiyamato, Tokyo, Japan
¹⁶ Department of Surgery, National Center for Child Health and Development, Tokyo, Japan
¹⁷ Second Department of Internal Medicine, Fukui Medical University, Fukui, Japan

Correspondence to:
Correspondence to:
Dr N Wakamatsu
Department of Genetics, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, Aichi 480-0392, Japan; nwaka@inst-hsc.jp

Received 4 November 2003

Accepted 18 January 2004

Keywords: 2q22; deletion; mental retardation; ZFHX1B

Abbreviations: GER, gastroesophageal reflux; HSCR, Hirschsprung disease; PAS, pulmonary artery sling; PDA, patent ductus arteriosus; TOF, tetralogy of Fallot

The first 150 words of the full text of this article appear below.

Hirschsprung disease (HSCR), a clinically complex syndrome often associated with a combination of mental retardation, microcephaly, and characteristic facial features, is genetically heterogeneous.^1–10 Recently, mutations in ZFHX1B, which encodes Smad-interacting protein 1 (SIP1), were identified by our group¹¹ and Cacheux et al¹² in patients with t(2;13)(q22;q22) and t(2;11)(q22.2;q21), respectively. These patients had clinical profiles consistent with a dominant form of the disease (Mowat-Wilson syndrome: MIM 235730).^9,13 These and subsequent articles have demonstrated a link between patients with nonsense and frameshift mutations of the gene and the presence in these patients of the following clinical findings: profound mental retardation, delayed motor development, and specific facial features, including hypertelorism, a broad nasal bridge, strabismus, a pointed chin, prognathism, a nose with a prominent columella, and posteriorly rotated ears. Often associated with these features were microcephaly, epilepsy, congenital heart disease, HSCR, and midline defects such as agenesis or hypoplasia of the corpus . . . [Full text of this article]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Ohtsuka, M., Oguni, H., Ito, Y., Nakayama, T., Matsuo, M., Osawa, M., Saito, K., Yamada, Y., Wakamatsu, N. (2008). Mowat-Wilson Syndrome Affecting 3 Siblings. J Child Neurol 23: 274-278 [Abstract]  
• Van de Putte, T., Francis, A., Nelles, L., van Grunsven, L. A., Huylebroeck, D. (2007). Neural crest-specific removal of Zfhx1b in mouse leads to a wide range of neurocristopathies reminiscent of Mowat-Wilson syndrome. Hum Mol Genet 16: 1423-1436 [Abstract] [Full Text]