First molecular study in Lebanese patients with Cockayne syndrome and report of a novel mutation in ERCC8 gene

Alain Chebly,Sandra Corbani,André Megarbane,Eliane Chouery,Cybel Mehawej,Joelle Abou Ghoch

doi:10.1186/s12881-018-0677-7

Alain Chebly, Sandra Corbani + Show 4 more

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https://doi.org/10.1186/s12881-018-0677-7

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Abstract

BackgroundCockayne Syndrome (CS) is a rare autosomal recessive disorder characterized by neurological and sensorial impairment, dwarfism, microcephaly and photosensitivity. CS is caused by mutations in ERCC6 (CSB) or ERCC8 (CSA) genes.MethodsThree patients with CS were referred to the Medical Genetics Unit of Saint Joseph University. Sanger sequencing of both ERCC8 and ERCC6 genes was performed: ERCC8 was tested in all patients while ERCC6 in one of them.ResultsSequencing led to the identification of three homozygous mutations, two in ERCC8 (p.Y322* and c.843 + 1G > C) and one in ERCC6 (p.R670W). All mutations were previously reported as pathogenic except for the c.843 + 1G > C splice site mutation in ERCC8 which is novel.ConclusionsMolecular diagnosis was established in all patients included in our study. A genotype-phenotype correlation is discussed and a link, between mutations and some specific religious communities in Lebanon, is suggested.

Highlights

Cockayne Syndrome (CS) is a rare autosomal recessive disorder characterized by neurological and sensorial impairment, dwarfism, microcephaly and photosensitivity
Testing of Excision Repair Cross-Complementation group 8 (ERCC8) did not reveal any mutation in patient B, a homozygous mutation in exon 10 of the Excision Repair Cross-Complementation group 6 (ERCC6) gene (NM_000124.3:c.2008C > T; p.R670W) was detected in this patient (Fig. 3b)
Genetic evaluation of patient C led to the identification of a novel homozygous variant in ERCC8 (NM_000082.3:c.843 + 1G > C) altering the donor splice site of intron 9 of the gene (Fig. 3c)

Summary

Introduction

Cockayne Syndrome (CS) is a rare autosomal recessive disorder characterized by neurological and sensorial impairment, dwarfism, microcephaly and photosensitivity. Cockayne syndrome (CS; MIM# 133540, 216400) is a rare autosomal recessive disorder belonging to the family of premature aging syndromes It was first described by Edward Alfred Cockayne, a British physician, in 1936 in a paper entitled “Dwarfism with retinal atrophy and deafness”, followed ten years later by another paper reporting a follow up data on the same patients [1, 2]. For instance, found in almost 50% of CS patients, This rare disease is linked to mutations in one of two excision-repair cross-complementation genes ERCC6 (CSB) and ERCC8 (CSA). These genes encode proteins involved in the transcription-coupled sub-pathway of nucleotide excision repair (TC-NER) of UV-induced DNA damage [11, 12]. CSA interacts with CSB and Chebly et al BMC Medical Genetics (2018)9:6

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