Functional monosomy of 6q27-qter and functional disomy of Xpter-p22.11 due to X;6 translocation with an atypical X-inactivation pattern.
Am J Med Genet A
; 173(5): 1334-1341, 2017 May.
Article
em En
| MEDLINE
| ID: mdl-28371302
ABSTRACT
Pattern of X chromosome inactivation (XCI) is typically random in females. However, chromosomal rearrangements affecting the X chromosome can result in XCI skewing due to cell growth disadvantage. In case of an X;autosome translocation, this usually leads to an XCI pattern of 1000 with the derivative X being the active one in the majority of females. A de novo balanced X;6 translocation [46,X,t(X;6)(p22.1;q27)] and a completely skewed XCI pattern (1000) were detected in a female patient with microcephaly, cerebellar vermis hypoplasia, heart defect, and severe developmental delay. We mapped the breakpoint regions using fluorescence in situ hybridization and found the X-linked gene POLA1 to be disrupted. POLA1 codes for the catalytic subunit of the polymerase α-primase complex which is responsible for initiation of the DNA replication process; absence of POLA1 is probably incompatible with life. Consequently, by RBA banding we determined which of the X chromosomes was the active one in the patient. In all examined lymphocytes the wild-type X chromosome was active. We propose that completely skewed XCI favoring the normal X chromosome resulted from death of cells with an active derivative X that was caused by a non-functional POLA1 gene. In summary, we conclude that functional monosomy of 6q27-qter and functional disomy of Xpter-p22.11 are responsible for the clinical phenotype of the patient. This case demonstrates the importance of determining which one of the X chromosomes underwent inactivation to correlate clinical features of a female with an X;autosome translocation with the nature of the genetic alteration.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deficiências do Desenvolvimento
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Cromossomos Humanos X
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DNA Polimerase III
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Inativação do Cromossomo X
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Microcefalia
Limite:
Adult
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Female
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Humans
Idioma:
En
Revista:
Am J Med Genet A
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Alemanha