Open AccessCOQ8A and MED25 Mutations in a Child with Intellectual Disability, Microcephaly, Seizures, and Spastic Ataxia: Synergistic Effect of Digenic Variants
Author(s) -
Pratibha Nair,
Maher Lama,
Stephany ElHayek,
Gretta Abou-Sleymane,
Samantha Stora,
Marc Obeid,
Mahmoud Taleb AlAli,
Valérie Delague,
André Mégarbané
Publication year - 2018
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000494465
Subject(s) - microcephaly , exome sequencing , intellectual disability , ataxia , short stature , medicine , genetics , pediatrics , spastic quadriplegia , phenotype , cerebral palsy , gene , biology , psychiatry
We report on a girl, born to first-cousin Lebanese parents, with severe intellectual disability, congenital hip luxation, cardiac malformation, short stature, facial dysmorphic features including microcephaly, sparse hair, bilateral epicanthal folds, ataxia, seizures, and elevated lactate and pyruvate levels in serum. Whole exome sequencing was carried out on the patient's DNA. Potentially causal homozygous variants in the MED25 (p.Ile173Thr) and COQ8A (p.Arg512Trp) genes were found. The potential pathogenicity of these variants, and the possibility that the 2 variants could synergistically act to produce the phenotype reported, is discussed.