CLINICAL REPORT A Homozygous Mutation in RNU4ATAC as a Cause of Microcephalic Osteodysplastic Primordial Dwarfism Type I (MOPD I) With Associated Pigmentary Disorder Ghada M.H. Abdel-Salam, 1 * Noriko Miyake, 2 Maha M. Eid, 3 Mohamed S. Abdel-Hamid, 4 Nihal A. Hassan, 5 Ola M. Eid, 3 Laila K. Effat, 4 Tarek H. El-Badry, 6 Ghada Y. El-Kamah, 1 Mohamed El-Darouti, 7 and Naomichi Matsumoto 2 ** 1 Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt 2 Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan 3 Human Cytogenetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt 4 Medical Molecular Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt 5 Ophthalmology Department, Faculty of Medicine, Cairo University, Cairo, Egypt 6 Orodental Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt 7 Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt Received 3 July 2011; Accepted 17 August 2011 The designation microcephalic osteodysplastic primordial dwarfism (MOPD) refers to a group of autosomal recessive disorders, comprising microcephaly, growth retardation, and a skeletal dysplasia. The different types of MOPD have been delineated on the basis of clinical, radiological, and genetic criteria. We describe two brothers, born to healthy, consangui- neous parents, with intrauterine and postnatal growth retarda- tion, microcephaly with abnormal gyral pattern and partial agenesis of corpus callosum, and skeletal anomalies reminiscent of those described in MOPD type I. This was confirmed by the identification of the homozygous g.55G > A mutation of RNU4ATAC encoding U4atac snRNA. The sibs had yellowish- gray hair, fair skin, and deficient retinal pigmentation. Skin biopsy showed abnormal melanin function but OCA genes were normal. The older sib had an intracranial hemorrhage at 1 week after birth, the younger developed chilblains-like lesions at the age 2 1 / 2 years old but analysis of the SAMHD1 and TREX1 genes did not show any mutations. To the best of our knowledge, vasculopathy and pigmentary disorders have not been reported in MOPD I. Ó 2011 Wiley Periodicals, Inc. Key words: microcephalic osteodysplastic primordial dwarfism I (MOPD I); abnormal gyral pattern; pigmentary disorder; hypo- genesis of corpus callosum; chilblains; fair skin; U4atac snRNA; vasculopathy; retinal pigmentation; microdontia INTRODUCTION The term ‘‘microcephalic osteodysplastic primordial dwarfism’’ (MOPD) refers to the entities Seckel syndrome and microcephaly osteodysplastic primordial dwarfism (MOPD) type I/III and type II [Majewski et al., 1982; Meinecke and Passarge, 1991]. Variants of MOPD or Seckel-like syndrome have been described [Shebib et al., 1991; Buebel et al., 1996]. They share common findings such as severe intrauterine and postnatal growth retardation, microcephaly, Additional supporting information may be found in the online version of this article. *Correspondence to: Ghada M.H. Abdel-Salam, Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Tahrir Street, Dokki, Cairo, Egypt. E-mail: ghada.abdelsalam@yahoo.com, ghasala@hotmail.com **Correspondence to: Naomichi Matsumoto, Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. E-mail: naomat@yokohama-cu.ac.jp Published online 11 October 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ajmg.a.34299 How to Cite this Article: Abdel-Salam GMH, Miyake N, Eid MM, Abdel-Hamid MS, Hassan NA, Eid OM, Effat LK, El-Badry TH, El-Kamah GY, El-Darouti M, Matsumoto N. 2011. A homozygous mutation in RNU4ATAC as a cause of microcephalic osteodysplastic primordial dwarfism type I (MOPD I) with associated pigmentary disorder. Am J Med Genet Part A 155:2885–2896. Ó 2011 Wiley Periodicals, Inc. 2885