title: Diagnosis of cystathionine beta-synthase deficiency by genetic analysis.
abstract: Intellectual disability like other common diseases is often complex because they are genetically heterogeneous, with many different genetic defects giving rise to clinically indistinguishable phenotypes. We present diagnosis of cystathionine beta-synthase (CBS) deficiency in a multiply affected Iranian family with obvious intellectual disability based on whole genome SNP homozygosity mapping. Diagnosis based on clinical presentations had not been made because of unavailability of appropriate medical services. Genetic analysis led to identification of homozygous c.346G>A in CBS that causes p.Gly116Arg in the encoded protein, cystathionine beta-synthase. CBS is the most common causative gene of homocystinurea. Later, the same mutation was found in three other apparently unrelated Iranian homocystinuria patients. p.Gly116Arg was reported once before in a Turkish patient, suggesting it may be a common CBS deficiency causing mutation in the Middle East. Clinical features of the patients are reported that evidence to variable presentations caused by the same mutation. Finally, observations in heterozygous carriers of the mutation suggest data that a single allele of the p.Gly116Arg causing mutation may have phenotypic consequences, including cardiac related phenotypes. Our study attests to the powers of genetic analysis for diagnosis especially for some forms of intellectual disability, with known genetic causing agents.
authors.affiliation: School of Biology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Suri
authors.affiliation: Genetics of Non-communicable Disease Research Center, Zahedan University of Medical Science, Zahedan, Iran.
authors.forename: Mehrnaz
authors.initials: M
authors.lastname: Narooie-Nejad
authors.affiliation: School of Biology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Iman
authors.initials: I
authors.lastname: Safari
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Moazzeni
authors.affiliation: Division of Ophthalmology, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Rohani
authors.affiliation: Children and Adolescent Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Khajeh
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Brandy
authors.initials: B
authors.lastname: Klotzle
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: School of Biology, College of Science, University of Tehran, Tehran, Iran; Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran. Electronic address: elahe.elahi@gmail.com.
authors.forename: Elahe
authors.initials: E
authors.lastname: Elahi
mesh_terms: D000293:Adolescent; D000328:Adult; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006712:Homocystinuria / Q000150:complications* / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014421:Turkey; D055815:Young Adult
chemical_list: D003541:Cystathionine beta-Synthase
keywords: Cystathionine beta-synthase (CBS); Diagnosis; Homocystinuria; Intellectual disability; Whole genome SNP homozygosity mapping; p.Gly116Arg