Limits...
Fatal respiratory disease due to a homozygous intronic ABCA3 mutation: a case report

View Article: PubMed Central - PubMed

ABSTRACT

Background: Pulmonary surfactant is a complex mixture of lipids and proteins. Mutations in surfactant protein-C, surfactant protein-D, and adenosine triphosphate-binding cassette subfamily A member 3 have been related to surfactant dysfunction and neonatal respiratory failure in full-term babies. Adenosine triphosphate-binding cassette subfamily A member 3 facilitates the transfer of lipids to lamellar bodies. We report the case of patient with a homozygous intronic ABCA3 mutation.

Case presentation: We describe a newborn full-term Colombian baby boy who was the son of non-consanguineous parents of mixed race ancestry (Mestizo), who was delivered with severe respiratory depression. Invasive treatment was unsuccessful and diagnosis was uncertain. Exons 4 and 5 of the SP-C gene showed heterozygous Thr138Asn polymorphism and homozygous Asn186Asn polymorphism respectively. At intron 25 at position –98 from exon 26 a homozygous C>T transition mutation was detected in ABCA3 gene.

Conclusions: The clinical presentation and the histopathological findings of this case are consistent with a case of neonatal respiratory failure due to surfactant deficiency. Analysis of the five coding SP-C exons does not support surfactant deficiency. An analysis of the mutation IVS25-98 T was performed and a homozygous mutation responsible for our case’s neonatal respiratory failure was detected. The findings suggest an autosomic recessive pattern of inheritance. Genetic counseling was provided and the relatives are now informed of the recurrence risks and treatment options.

No MeSH data available.


ABCA3, exon 26 sequence from 45981 to 46336 showing homozygous mutation IVS25 (gttacaggTgccttgag)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC5037624&req=5

Fig3: ABCA3, exon 26 sequence from 45981 to 46336 showing homozygous mutation IVS25 (gttacaggTgccttgag)

Mentions: Due to the uncertainty of the diagnosis a literature review was performed and experts were asked for advice. A search for a specific mutation in the intronic region of the ABCA3 gene was performed. In intron 25 at position –98 from exon 26 a homozygous C>T transition mutation was detected. This mutation changes the intronic sequence, creates a new donor splice site and leads to aberrant ABCA3 proteins and is the cause of our patient’s fatal respiratory disease (Fig. 3).Fig. 3


Fatal respiratory disease due to a homozygous intronic ABCA3 mutation: a case report
ABCA3, exon 26 sequence from 45981 to 46336 showing homozygous mutation IVS25 (gttacaggTgccttgag)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5037624&req=5

Fig3: ABCA3, exon 26 sequence from 45981 to 46336 showing homozygous mutation IVS25 (gttacaggTgccttgag)
Mentions: Due to the uncertainty of the diagnosis a literature review was performed and experts were asked for advice. A search for a specific mutation in the intronic region of the ABCA3 gene was performed. In intron 25 at position –98 from exon 26 a homozygous C>T transition mutation was detected. This mutation changes the intronic sequence, creates a new donor splice site and leads to aberrant ABCA3 proteins and is the cause of our patient’s fatal respiratory disease (Fig. 3).Fig. 3

View Article: PubMed Central - PubMed

ABSTRACT

Background: Pulmonary surfactant is a complex mixture of lipids and proteins. Mutations in surfactant protein-C, surfactant protein-D, and adenosine triphosphate-binding cassette subfamily A member 3 have been related to surfactant dysfunction and neonatal respiratory failure in full-term babies. Adenosine triphosphate-binding cassette subfamily A member 3 facilitates the transfer of lipids to lamellar bodies. We report the case of patient with a homozygous intronic ABCA3 mutation.

Case presentation: We describe a newborn full-term Colombian baby boy who was the son of non-consanguineous parents of mixed race ancestry (Mestizo), who was delivered with severe respiratory depression. Invasive treatment was unsuccessful and diagnosis was uncertain. Exons 4 and 5 of the SP-C gene showed heterozygous Thr138Asn polymorphism and homozygous Asn186Asn polymorphism respectively. At intron 25 at position –98 from exon 26 a homozygous C>T transition mutation was detected in ABCA3 gene.

Conclusions: The clinical presentation and the histopathological findings of this case are consistent with a case of neonatal respiratory failure due to surfactant deficiency. Analysis of the five coding SP-C exons does not support surfactant deficiency. An analysis of the mutation IVS25-98 T was performed and a homozygous mutation responsible for our case’s neonatal respiratory failure was detected. The findings suggest an autosomic recessive pattern of inheritance. Genetic counseling was provided and the relatives are now informed of the recurrence risks and treatment options.

No MeSH data available.