Article
Segmental Uniparental Isodisomy of Chromosome 6 Causing Transient Diabetes Mellitus and Merosin-Deficient Congenital Muscular Dystrophy
Registro en:
ANDRADE, Raissa Coelho et al. Segmental Uniparental Isodisomy of Chromosome 6 Causing Transient Diabetes Mellitus and Merosin-Deficient Congenital Muscular Dystrophy. American Journal of Medical Genetics Part A, v.164,n.11, p.2908–2913, Nov. 2014.
1552-4833
Autor
Andrade, Raissa Coelho
Nevado, Julián
Lima, Maria Angélica de Faria Domingues de
Salles, Tania Regina Dias Saad
Moraes, Lucia
Chimelli, Leila
Lapunzina, Pablo
Vargas, Fernando Regla
Resumen
Segmental uniparental isodisomy (iUPD) is a rare genetic event
that may cause aberrant expression of imprinted genes, and
reduction to homozygosity of a recessive mutation. Transient
neonatal diabetes mellitus (TNDM) is typically caused by imprinting
aberrations in chromosome 6q24 TNDMdifferentiallymethylated
region (DMR). Approximately, 15.12Mb upstream
in 6q22-q23 is located LAMA2, the gene responsible of merosindeficient
congenital muscular dystrophy type 1A (MDC1A).We
investigated a patient diagnosed both with TNDMand MDC1A,
born from a twin dichorionic discordant pregnancy. Parents are
first-degree cousins. Methylation sensitive-PCR of the imprinted
6q24 TNDM CpG island showed only the non-methylated (paternal)
allele. Microsatellite markers and SNP array profiling
disclosed normal biparental inheritance at 6p and a segmental
paternal iUPD, between 6q22.33 and 6q27. Sequencing of
LAMA2 exons showed a homozygous frameshift mutation,
c.7490_7493dupAAGA, which predicts p.Asp2498GlufsX4, in
exon 54. Her father, but not her mother, was a carrier of the
mutation. While segmental paternal iUPD6 causing TNDM was
reported twice, there are no previous reports of MDC1A caused
by this event. This is a child with two genetic disorders, yet
neither is caused by the parental consanguinity, which reinforces
the importance of considering different etiological mechanisms
in the genetic clinic.