A novel mutation in ERCC8 gene causing cockayne syndrome

Maryam Taghdiri, Hassan Dastsooz, Majid Fardaei, Sanaz Mohammadi, Mohammad Ali Farazi Fard, Mohammad A Faghihi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Cockayne syndrome (CS) is a rare autosomal recessive multisystem disorder characterized by impaired neurological and sensory functions, cachectic dwarfism, microcephaly, and photosensitivity. This syndrome shows a variable age of onset and rate of progression, and its phenotypic spectrum include a wide range of severity. Due to the progressive nature of this disorder, diagnosis can be more important when additional signs and symptoms appear gradually and become steadily worse over time. Therefore, mutation analysis of genes involved in CS pathogenesis can be helpful to confirm the suspected clinical diagnosis. Here, we report a novel mutation in ERCC8 gene in a 16-year-old boy who suffers from poor weight gain, short stature, microcephaly, intellectual disability, and photosensitivity. The patient was born to consanguineous family with no previous documented disease in his parents. To identify disease-causing mutation in the patient, whole exome sequencing utilizing next-generation sequencing on an Illumina HiSeq 2000 platform was performed. Results revealed a novel homozygote mutation in ERCC8 gene (NM_000082: exon 11, c.1122G > C) in our patient. Another gene (ERCC6), which is also involved in CS did not have any disease-causing mutations in the proband. The new identified mutation was then confirmed by Sanger sequencing in the proband, his parents, and extended family members, confirming co-segregation with the disease. In addition, different bioinformatics programs which included MutationTaster, I-Mutant v2.0, NNSplice, Combined Annotation Dependent Depletion, The PhastCons, Genomic Evolutationary Rate Profiling conservation score, and T-Coffee Multiple Sequence Alignment predicted the pathogenicity of the mutation. Our study identified a rare novel mutation in ERCC8 gene and help to provide accurate genetic counseling and prenatal diagnosis to minimize new affected individuals in this family.

Original languageEnglish (US)
Article number169
JournalFrontiers in Pediatrics
Volume5
DOIs
StatePublished - Aug 9 2017

Fingerprint

Cockayne Syndrome
Mutation
Genes
Microcephaly
Parents
Exome
Dwarfism
Sequence Alignment
Coffee
Genetic Counseling
Homozygote
Computational Biology
Prenatal Diagnosis
Age of Onset
Intellectual Disability
Signs and Symptoms
Weight Gain
Virulence
Exons

Keywords

  • Cockayne syndrome
  • ERCC8
  • Intellectual disability
  • Neurodevelopmental disorders
  • Novel mutation
  • Rare inherited disorders

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Taghdiri, M., Dastsooz, H., Fardaei, M., Mohammadi, S., Fard, M. A. F., & Faghihi, M. A. (2017). A novel mutation in ERCC8 gene causing cockayne syndrome. Frontiers in Pediatrics, 5, [169]. https://doi.org/10.3389/fped.2017.00169

A novel mutation in ERCC8 gene causing cockayne syndrome. / Taghdiri, Maryam; Dastsooz, Hassan; Fardaei, Majid; Mohammadi, Sanaz; Fard, Mohammad Ali Farazi; Faghihi, Mohammad A.

In: Frontiers in Pediatrics, Vol. 5, 169, 09.08.2017.

Research output: Contribution to journalArticle

Taghdiri, Maryam ; Dastsooz, Hassan ; Fardaei, Majid ; Mohammadi, Sanaz ; Fard, Mohammad Ali Farazi ; Faghihi, Mohammad A. / A novel mutation in ERCC8 gene causing cockayne syndrome. In: Frontiers in Pediatrics. 2017 ; Vol. 5.
@article{c55dde2a72cd428ab9983448af4cfca3,
title = "A novel mutation in ERCC8 gene causing cockayne syndrome",
abstract = "Cockayne syndrome (CS) is a rare autosomal recessive multisystem disorder characterized by impaired neurological and sensory functions, cachectic dwarfism, microcephaly, and photosensitivity. This syndrome shows a variable age of onset and rate of progression, and its phenotypic spectrum include a wide range of severity. Due to the progressive nature of this disorder, diagnosis can be more important when additional signs and symptoms appear gradually and become steadily worse over time. Therefore, mutation analysis of genes involved in CS pathogenesis can be helpful to confirm the suspected clinical diagnosis. Here, we report a novel mutation in ERCC8 gene in a 16-year-old boy who suffers from poor weight gain, short stature, microcephaly, intellectual disability, and photosensitivity. The patient was born to consanguineous family with no previous documented disease in his parents. To identify disease-causing mutation in the patient, whole exome sequencing utilizing next-generation sequencing on an Illumina HiSeq 2000 platform was performed. Results revealed a novel homozygote mutation in ERCC8 gene (NM_000082: exon 11, c.1122G > C) in our patient. Another gene (ERCC6), which is also involved in CS did not have any disease-causing mutations in the proband. The new identified mutation was then confirmed by Sanger sequencing in the proband, his parents, and extended family members, confirming co-segregation with the disease. In addition, different bioinformatics programs which included MutationTaster, I-Mutant v2.0, NNSplice, Combined Annotation Dependent Depletion, The PhastCons, Genomic Evolutationary Rate Profiling conservation score, and T-Coffee Multiple Sequence Alignment predicted the pathogenicity of the mutation. Our study identified a rare novel mutation in ERCC8 gene and help to provide accurate genetic counseling and prenatal diagnosis to minimize new affected individuals in this family.",
keywords = "Cockayne syndrome, ERCC8, Intellectual disability, Neurodevelopmental disorders, Novel mutation, Rare inherited disorders",
author = "Maryam Taghdiri and Hassan Dastsooz and Majid Fardaei and Sanaz Mohammadi and Fard, {Mohammad Ali Farazi} and Faghihi, {Mohammad A}",
year = "2017",
month = "8",
day = "9",
doi = "10.3389/fped.2017.00169",
language = "English (US)",
volume = "5",
journal = "Frontiers in Pediatrics",
issn = "2296-2360",
publisher = "Frontiers Media S. A.",

}

TY - JOUR

T1 - A novel mutation in ERCC8 gene causing cockayne syndrome

AU - Taghdiri, Maryam

AU - Dastsooz, Hassan

AU - Fardaei, Majid

AU - Mohammadi, Sanaz

AU - Fard, Mohammad Ali Farazi

AU - Faghihi, Mohammad A

PY - 2017/8/9

Y1 - 2017/8/9

N2 - Cockayne syndrome (CS) is a rare autosomal recessive multisystem disorder characterized by impaired neurological and sensory functions, cachectic dwarfism, microcephaly, and photosensitivity. This syndrome shows a variable age of onset and rate of progression, and its phenotypic spectrum include a wide range of severity. Due to the progressive nature of this disorder, diagnosis can be more important when additional signs and symptoms appear gradually and become steadily worse over time. Therefore, mutation analysis of genes involved in CS pathogenesis can be helpful to confirm the suspected clinical diagnosis. Here, we report a novel mutation in ERCC8 gene in a 16-year-old boy who suffers from poor weight gain, short stature, microcephaly, intellectual disability, and photosensitivity. The patient was born to consanguineous family with no previous documented disease in his parents. To identify disease-causing mutation in the patient, whole exome sequencing utilizing next-generation sequencing on an Illumina HiSeq 2000 platform was performed. Results revealed a novel homozygote mutation in ERCC8 gene (NM_000082: exon 11, c.1122G > C) in our patient. Another gene (ERCC6), which is also involved in CS did not have any disease-causing mutations in the proband. The new identified mutation was then confirmed by Sanger sequencing in the proband, his parents, and extended family members, confirming co-segregation with the disease. In addition, different bioinformatics programs which included MutationTaster, I-Mutant v2.0, NNSplice, Combined Annotation Dependent Depletion, The PhastCons, Genomic Evolutationary Rate Profiling conservation score, and T-Coffee Multiple Sequence Alignment predicted the pathogenicity of the mutation. Our study identified a rare novel mutation in ERCC8 gene and help to provide accurate genetic counseling and prenatal diagnosis to minimize new affected individuals in this family.

AB - Cockayne syndrome (CS) is a rare autosomal recessive multisystem disorder characterized by impaired neurological and sensory functions, cachectic dwarfism, microcephaly, and photosensitivity. This syndrome shows a variable age of onset and rate of progression, and its phenotypic spectrum include a wide range of severity. Due to the progressive nature of this disorder, diagnosis can be more important when additional signs and symptoms appear gradually and become steadily worse over time. Therefore, mutation analysis of genes involved in CS pathogenesis can be helpful to confirm the suspected clinical diagnosis. Here, we report a novel mutation in ERCC8 gene in a 16-year-old boy who suffers from poor weight gain, short stature, microcephaly, intellectual disability, and photosensitivity. The patient was born to consanguineous family with no previous documented disease in his parents. To identify disease-causing mutation in the patient, whole exome sequencing utilizing next-generation sequencing on an Illumina HiSeq 2000 platform was performed. Results revealed a novel homozygote mutation in ERCC8 gene (NM_000082: exon 11, c.1122G > C) in our patient. Another gene (ERCC6), which is also involved in CS did not have any disease-causing mutations in the proband. The new identified mutation was then confirmed by Sanger sequencing in the proband, his parents, and extended family members, confirming co-segregation with the disease. In addition, different bioinformatics programs which included MutationTaster, I-Mutant v2.0, NNSplice, Combined Annotation Dependent Depletion, The PhastCons, Genomic Evolutationary Rate Profiling conservation score, and T-Coffee Multiple Sequence Alignment predicted the pathogenicity of the mutation. Our study identified a rare novel mutation in ERCC8 gene and help to provide accurate genetic counseling and prenatal diagnosis to minimize new affected individuals in this family.

KW - Cockayne syndrome

KW - ERCC8

KW - Intellectual disability

KW - Neurodevelopmental disorders

KW - Novel mutation

KW - Rare inherited disorders

UR - http://www.scopus.com/inward/record.url?scp=85042049815&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042049815&partnerID=8YFLogxK

U2 - 10.3389/fped.2017.00169

DO - 10.3389/fped.2017.00169

M3 - Article

AN - SCOPUS:85042049815

VL - 5

JO - Frontiers in Pediatrics

JF - Frontiers in Pediatrics

SN - 2296-2360

M1 - 169

ER -