Grand paternal inheritance of X-linked myotubular myopathy due to mosaicism, and identification of necklace fibers in an asymptomatic male.

Oldfors Hedberg, Carola,1969Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology (författare)

X-linked recessive myotubular myopathy (XLMTM) is a disorder associated with mutations in the myotubularin gene (MTM1) that usually affects boys, with transmission of the mutated allele from the mother. Here we describe a family with unexpected grand paternal transmission of a novel mutation in MTM1 (c.646_648dupGTT; p.Val216dup) identified in a severely affected infant boy with a centronuclear myopathy. We confirmed the carrier status of the mother, but surprisingly we found that her father was a carrier of the mutated MTM1 gene together with wild-type MTM1. A muscle biopsy from the grandfather revealed occasional typical necklace fibers with internalized nucleus, which is typically found in MTM1-associated myopathies. Further analysis of the grandfather revealed equal amounts of DNA with the wild-type sequence and DNA with the c.646_648dupGTT variant in five different tissues examined. In the presence of a normal karyotype (46,XY) in the grandfather and no evidence of intragenic duplication of MTM1, the result was interpreted as postzygotic mosaicism and the mutation had probably occurred at the first mitosis of the zygote. This study demonstrates the importance of considering the possibility of paternal transmission in families with severe X-linked disorders. The muscle biopsy with the finding of typical necklace fibers was important to further establish the pathogenicity of the novel MTM1 mutation.

Visuttijai, KittichateGothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine(Swepub:gu)xviski (författare)
Tulinius, Mar,1953Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics(Swepub:gu)xtulim (författare)
Oldfors, Anders,1951Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology(Swepub:gu)xoland (författare)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för patologi (creator_code:org_t)

Ingår i:Neuromuscular disorders : NMD: Elsevier BV27:9, s. 843-8471873-23640960-8966

Av författaren/redakt...: Oldfors Hedberg, ...; Visuttijai, Kitt ...; Tulinius, Mar, 1 ...; Oldfors, Anders, ...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Pediatrik

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