Dataset Information

Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency.

ABSTRACT: We have identified two families with a previously undescribed lethal X-linked disorder of infancy; the disorder comprises a distinct combination of an aged appearance, craniofacial anomalies, hypotonia, global developmental delays, cryptorchidism, and cardiac arrhythmias. Using X chromosome exon sequencing and a recently developed probabilistic algorithm aimed at discovering disease-causing variants, we identified in one family a c.109T>C (p.Ser37Pro) variant in NAA10, a gene encoding the catalytic subunit of the major human N-terminal acetyltransferase (NAT). A parallel effort on a second unrelated family converged on the same variant. The absence of this variant in controls, the amino acid conservation of this region of the protein, the predicted disruptive change, and the co-occurrence in two unrelated families with the same rare disorder suggest that this is the pathogenic mutation. We confirmed this by demonstrating a significantly impaired biochemical activity of the mutant hNaa10p, and from this we conclude that a reduction in acetylation by hNaa10p causes this disease. Here we provide evidence of a human genetic disorder resulting from direct impairment of N-terminal acetylation, one of the most common protein modifications in humans.

SUBMITTER: Rope AF

PROVIDER: S-EPMC3135802 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency.

Rope Alan F AF Wang Kai K Evjenth Rune R Xing Jinchuan J Johnston Jennifer J JJ Swensen Jeffrey J JJ Johnson W Evan WE Moore Barry B Huff Chad D CD Bird Lynne M LM Carey John C JC Opitz John M JM Stevens Cathy A CA Jiang Tao T Schank Christa C Fain Heidi Deborah HD Robison Reid R Dalley Brian B Chin Steven S South Sarah T ST Pysher Theodore J TJ Jorde Lynn B LB Hakonarson Hakon H Lillehaug Johan R JR Biesecker Leslie G LG Yandell Mark M Arnesen Thomas T Lyon Gholson J GJ

American journal of human genetics 20110623 1

We have identified two families with a previously undescribed lethal X-linked disorder of infancy; the disorder comprises a distinct combination of an aged appearance, craniofacial anomalies, hypotonia, global developmental delays, cryptorchidism, and cardiac arrhythmias. Using X chromosome exon sequencing and a recently developed probabilistic algorithm aimed at discovering disease-causing variants, we identified in one family a c.109T>C (p.Ser37Pro) variant in NAA10, a gene encoding the cataly ...[more]

PMID: 21700266

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Dataset Information

Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency.

Publications

Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency.

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