Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis.
Mol Genet Genomic Med
; 9(11): e1838, 2021 11.
Article
in En
| MEDLINE
| ID: mdl-34655177
ABSTRACT
BACKGROUND:
Combined methylmalonic acidemia and homocystinuria is a rare inherited disorder of intracellular cobalamin metabolism caused by biallelic variants in one of the following genes MMACHC (cblC), MMADHC (cblD), LMBRD1 (cblF), ABCD4 (cblJ), THAP11 (cblX-like), and ZNF143 (cblX-like), or a hemizygous variant in HCFC1 (cblX). Prenatal diagnosis of combined methylmalonic acidemia with homocystinuria is crucial for high-risk couples since the disorder can be life-threatening for offspring. We would like to describe two infant deaths both of which are likely attributable to cblC despite not having a genetic confirmation, and subsequent pregnancy and prenatal genetic testing.METHODS:
Parental clinical exome sequencing and targeted Sanger sequencing of MMACHC gene in amniotic fluid was performed to check the carrier status of the fetus.RESULTS:
Parental clinical exome sequencing revealed a heterozygous pathogenic variant [NM_015506.2c.217C>T (p.Arg73*)] in the MMACHC gene of the mother and [NM_015506.2c.609G>A (p.Trp203*)] in the MMACHC gene of the father. Targeted Sanger sequencing of MMACHC gene in amniotic fluid revealed that the fetus carried only one nonsense variant [NM_015506.2c.609G>A (p.Trp203*)], which was inherited from the father. The mother delivered a healthy baby and the neonate did not show any symptoms or signs of combined methylmalonic acidemia and homocystinuria after birth.CONCLUSION:
We present a case of prenatal diagnosis with parental exome sequencing, which successfully diagnosed the carrier status of the fetus and parents in a combined methylmalonic acidemia and homocystinuria family.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Homocystinuria
Type of study:
Diagnostic_studies
Limits:
Female
/
Humans
/
Infant
/
Newborn
/
Pregnancy
Language:
En
Journal:
Mol Genet Genomic Med
Year:
2021
Document type:
Article