Dataset Information

A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 (GDF3) in a female with unilateral anophthalmia and skeletal anomalies.

ABSTRACT:

Purpose

The genetic causes of anophthalmia, microphthalmia and coloboma remain poorly understood. Missense mutations in Growth/Differentiation Factor 3 (GDF3) gene have previously been reported in patients with microphthalmia, iridial and retinal colobomas, Klippel-Feil anomaly with vertebral fusion, scoliosis, rudimentary 12th ribs and an anomalous right temporal bone. We used whole exome sequencing with a trio approach to study a female with unilateral anophthalmia, kyphoscoliosis and additional skeletal anomalies.

Observations

Exome sequencing revealed that the proposita was heterozygous for c.796C > T, predicting p.Arg266Cys, in GDF3. Sanger sequencing confirmed the mutation and showed that the unaffected mother was heterozygous for the same missense substitution.

Conclusions and importance

Although transfection studies with the p.Arg266Cys mutation have shown that this amino acid substitution is likely to impair function, non-penetrance for the ocular defects was apparent in this family and has been observed in other families with sequence variants in GDF3. We conclude p.Arg266Cys and other GDF3 mutations can be non-penetrant, making pathogenicity more difficult to establish when sequence variants in this gene are present in patients with structural eye defects.

SUBMITTER: Bardakjian T

PROVIDER: S-EPMC5722175 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 (<i>GDF3</i>) in a female with unilateral anophthalmia and skeletal anomalies.

Bardakjian Tanya T Krall Max M Wu Di D Lao Richard R Tang Paul Ling-Fung PL Wan Eunice E Kopinsky Sarina S Schneider Adele A Kwok Pui-Yan PY Slavotinek Anne A

American journal of ophthalmology case reports 20170621

<h4>Purpose</h4>The genetic causes of anophthalmia, microphthalmia and coloboma remain poorly understood. Missense mutations in Growth/Differentiation Factor 3 (<i>GDF3</i>) gene have previously been reported in patients with microphthalmia, iridial and retinal colobomas, Klippel-Feil anomaly with vertebral fusion, scoliosis, rudimentary 12th ribs and an anomalous right temporal bone. We used whole exome sequencing with a trio approach to study a female with unilateral anophthalmia, kyphoscolios ...[more]

PMID: 29260090

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