title: A homozygous mutation in RNU4ATAC as a cause of microcephalic osteodysplastic primordial dwarfism type I (MOPD I) with associated pigmentary disorder.
abstract: 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, consanguineous parents, with intrauterine and postnatal growth retardation, 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 2½ 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.
authors: Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. ghada.abdelsalam@yahoo.com
authors: Ghada M H
authors: GM
authors: Abdel-Salam
authors: Noriko
authors: N
authors: Miyake
authors: Maha M
authors: MM
authors: Eid
authors: Mohamed S
authors: MS
authors: Abdel-Hamid
authors: Nihal A
authors: NA
authors: Hassan
authors: Ola M
authors: OM
authors: Eid
authors: Laila K
authors: LK
authors: Effat
authors: Tarek H
authors: TH
authors: El-Badry
authors: Ghada Y
authors: GY
authors: El-Kamah
authors: Mohamed
authors: M
authors: El-Darouti
authors: Naomichi
authors: N
authors: Matsumoto
mesh_terms: D000293:Adolescent; D061085:Agenesis of Corpus Callosum / Q000235:genetics / Q000473:pathology; D002675:Child, Preschool; D003241:Consanguinity; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology; D004392:Dwarfism / Q000235:genetics* / Q000473:pathology; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000473:pathology; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010808:Physical Examination; D010859:Pigmentation Disorders / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D012342:RNA, Small Nuclear / Q000032:analysis; D035781:Siblings
chemical_list: D012342:RNA, Small Nuclear