Further delineation of Temtamy syndrome of corpus callosum and ocular abnormalities.

Autor: Alrakaf L; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia., Al-Owain MA; Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Busehail M; Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Alotaibi MA; Clinical Genetic and Metabolic Department, King Saud Medical city, Riyadh, Saudi Arabia., Monies D; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia.; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Aldhalaan HM; Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Alhashem A; Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia., Al-Hassnan ZN; Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Rahbeeni ZA; Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Murshedi FA; Genetic and Developmental Medicine Clinic, Sultan Qaboos University Hospital, Muscat, Oman., Ani NA; Genetic and Developmental Medicine Clinic, Sultan Qaboos University Hospital, Muscat, Oman.; Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Al-Maawali A; Genetic and Developmental Medicine Clinic, Sultan Qaboos University Hospital, Muscat, Oman.; Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Ibrahim NA; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia., Abdulwahab FM; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia., Alsagob M; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia., Hashem MO; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia., Ramadan W; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia., Abouelhoda M; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia.; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Meyer BF; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia.; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Kaya N; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia., Maddirevula S; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia., Alkuraya FS; Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, Saudi Arabia.; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.; Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2018 Mar; Vol. 176 (3), pp. 715-721. Date of Electronic Publication: 2018 Jan 31.
DOI: 10.1002/ajmg.a.38615
Abstrakt: Temtamy syndrome is a syndromic form of intellectual disability characterized by ocular involvement, epilepsy and dysgenesis of the corpus callosum. After we initially mapped the disease to C12orf57, we noted a high carrier frequency of an ancient startloss founder mutation [c.1A>G; p.M1?] in our population, and variable phenotypic expressivity in newly identified cases. This study aims to combine 33 previously published patients with 23 who are described here for the first time to further delineate the phenotype of this syndrome. In addition to the known p.M1? founder, we describe four novel homozygous variants, thus increasing the number of Temtamy syndrome-related C12orf57 variants to seven, all but one predicted to be loss of function. While all patients presented with intellectual disability/developmental delay, the frequency of other phenotypic features was variable: 73.2% (41/56) had epilepsy, 63% (34/54) had corpus callosal abnormalities, 14.5% (8/55) had coloboma, and 16.4% (9/55) had microphthalmia. Our analysis also revealed a high frequency of less recognized features such as congenital heart disease (51.4%), and brain white matter abnormalities (38%, 19/50). We conclude that C12orf57 variants should be considered in the etiology of developmental delay/intellectual disability, even when typical syndromic features are lacking, especially in those who trace their ancestry to Saudi Arabia where a founder C12orf57 mutation is among the most common recessive causes of intellectual disability.
(© 2018 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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