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A Common Ancestral Asn242Ser Mutation in TMEM67 Identified in Multiple Iranian Families with Joubert Syndrome.
Public Health Genomics. 2017; 20(3):188-193.PH

Abstract

BACKGROUND

Joubert syndrome (JS) is a clinically and genetically heterogeneous group of rare neurodevelopmental disorder characterised by peculiar midbrain-hindbrain malformation, known as the "molar tooth" sign. JS can manifest a broad range of signs and symptoms. The most common features of JS are hypotonia, ataxia, developmental delay/intellectual disability, abnormal eye movements, and neonatal breathing abnormalities. To date, 29 genes have been shown to cause JS.

METHODS

We employed whole-genome single nucleotide polymorphism genotyping in a group of Iranian families with JS and Sanger sequencing of a known mutation associated with JS located in a single homozygous regions shared by affected members of the families.

RESULTS

Homozygosity mapping uncovered a shared ∼2.2-Mb run of homozygosity on chromosome 8q21.3-q22.1 encompassing the known JS-causing TMEM67 gene. Sanger sequencing of a known mutation (NM_153704.5: c.725A>G; p.Asn242Ser) in TMEM67 identified from studying another Iranian family using whole-exome sequencing confirmed the presence of the homozygous mutation in 22 affected members of 12 nuclear families. "Molar tooth" sign of brain magnetic resonance imaging, moderate-to-severe neurodevelopmental delay, and abnormal eye movements were the most common features of affected individuals. In addition, liver disease, seizure, behavioural abnormalities, failure to thrive, and kidney disease were observed variably in some of the patients.

CONCLUSION

We propose that Asn242Ser is a founder mutation in the Iranian population, which might explain a significant proportion of JS cases from eastern Iran. Therefore, screening for this variant should be considered for genetic testing in Iranian patients with JS. In addition, this finding is important for developing population-specific genetic testing in Iran.

Authors+Show Affiliations

Medical Genetics Research Centre, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28719906

Citation

Dehghani, MohammadReza, et al. "A Common Ancestral Asn242Ser Mutation in TMEM67 Identified in Multiple Iranian Families With Joubert Syndrome." Public Health Genomics, vol. 20, no. 3, 2017, pp. 188-193.
Dehghani M, Mojarad M, Ghayoor Karimiani E, et al. A Common Ancestral Asn242Ser Mutation in TMEM67 Identified in Multiple Iranian Families with Joubert Syndrome. Public Health Genomics. 2017;20(3):188-193.
Dehghani, M., Mojarad, M., Ghayoor Karimiani, E., Vahidi Mehrjardi, M. Y., Sahebalzamani, A., Ashrafzadeh, F., Beiraghi Toosi, M., Eslahi, A., Ahangari, N., Yassini, S. M., Hassanbeigi, A., Rasti, A., Kalantar, S. M., & Maroofian, R. (2017). A Common Ancestral Asn242Ser Mutation in TMEM67 Identified in Multiple Iranian Families with Joubert Syndrome. Public Health Genomics, 20(3), 188-193. https://doi.org/10.1159/000477560
Dehghani M, et al. A Common Ancestral Asn242Ser Mutation in TMEM67 Identified in Multiple Iranian Families With Joubert Syndrome. Public Health Genomics. 2017;20(3):188-193. PubMed PMID: 28719906.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Common Ancestral Asn242Ser Mutation in TMEM67 Identified in Multiple Iranian Families with Joubert Syndrome. AU - Dehghani,MohammadReza, AU - Mojarad,Majid, AU - Ghayoor Karimiani,Ehsan, AU - Vahidi Mehrjardi,Mohammad Yahya, AU - Sahebalzamani,Afsaneh, AU - Ashrafzadeh,Farah, AU - Beiraghi Toosi,Mehran, AU - Eslahi,Atiyeh, AU - Ahangari,Najmeh, AU - Yassini,Seyed Mojtaba, AU - Hassanbeigi,Afsaneh, AU - Rasti,Azam, AU - Kalantar,Seyed Mehdi, AU - Maroofian,Reza, Y1 - 2017/07/19/ PY - 2017/03/17/received PY - 2017/05/17/accepted PY - 2017/7/19/pubmed PY - 2018/4/24/medline PY - 2017/7/19/entrez KW - Ciliopathies KW - Founder mutation KW - Homozygosity KW - Iranian families KW - Joubert syndrome KW - TMEM67 SP - 188 EP - 193 JF - Public health genomics JO - Public Health Genomics VL - 20 IS - 3 N2 - BACKGROUND: Joubert syndrome (JS) is a clinically and genetically heterogeneous group of rare neurodevelopmental disorder characterised by peculiar midbrain-hindbrain malformation, known as the "molar tooth" sign. JS can manifest a broad range of signs and symptoms. The most common features of JS are hypotonia, ataxia, developmental delay/intellectual disability, abnormal eye movements, and neonatal breathing abnormalities. To date, 29 genes have been shown to cause JS. METHODS: We employed whole-genome single nucleotide polymorphism genotyping in a group of Iranian families with JS and Sanger sequencing of a known mutation associated with JS located in a single homozygous regions shared by affected members of the families. RESULTS: Homozygosity mapping uncovered a shared ∼2.2-Mb run of homozygosity on chromosome 8q21.3-q22.1 encompassing the known JS-causing TMEM67 gene. Sanger sequencing of a known mutation (NM_153704.5: c.725A>G; p.Asn242Ser) in TMEM67 identified from studying another Iranian family using whole-exome sequencing confirmed the presence of the homozygous mutation in 22 affected members of 12 nuclear families. "Molar tooth" sign of brain magnetic resonance imaging, moderate-to-severe neurodevelopmental delay, and abnormal eye movements were the most common features of affected individuals. In addition, liver disease, seizure, behavioural abnormalities, failure to thrive, and kidney disease were observed variably in some of the patients. CONCLUSION: We propose that Asn242Ser is a founder mutation in the Iranian population, which might explain a significant proportion of JS cases from eastern Iran. Therefore, screening for this variant should be considered for genetic testing in Iranian patients with JS. In addition, this finding is important for developing population-specific genetic testing in Iran. SN - 1662-8063 UR - https://www.unboundmedicine.com/medline/citation/28719906/A_Common_Ancestral_Asn242Ser_Mutation_in_TMEM67_Identified_in_Multiple_Iranian_Families_with_Joubert_Syndrome_ L2 - https://www.karger.com?DOI=10.1159/000477560 DB - PRIME DP - Unbound Medicine ER -