Ataxia-telangiectasia-like disorder in a family deficient for MRE11A, caused by a MRE11 variant

• Objective We report 3 siblings with the characteristic features of ataxia-telangiectasia-like disorder associated with a homozygous MREll synonymous variant causing nonsense-mediated mRNA decay (NMD) and MRE11A deficiency. Clinical assessments, next-generation sequencing, transcript and immunohistochemistry analyses were performed. The patients presented with poor balance, developmental delay during the first year of age, and suffered from intellectual disability from early childhood. They showed oculomotor apraxia, slurred and explosive speech, limb and gait ataxia, exaggerated deep tendon reflex, dystonic posture, and mirror movement in their hands. They developed mild cognitive abilities. Brain MRI in the index case revealed cerebellar atrophy. Next-generation sequencing revealed a homozygous synonymous variant in MRE11 (c.657C>T, p.Asn219=) that we show affects splicing. A complete absence of MREll transcripts in the index case suggested NMD and immunohistochemistry confirmed the absence of a stable protein. Despite the critical role of MRE11A in double-strand break repair and its contribution to the Mre11/Rad50/Nbs1 complex, the absence of MRE11A is compatible with life.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

strand break repair

DNA-repair

distinct

protein

gene

mutations

responses

defects

reveals

complex

Neurosciences & Neurology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)