Two unrelated pedigrees with achondrogenesis type 1b carrying a Japan‐specific pathogenic variant in SLC26A2

We present two unrelated Japanese pedigrees with achondrogenesis type 1b (ACG1B), characterized by prenatally lethal fetal hydrops and severe micromelia. The affected members in these pedigrees carried a common homozygous missense point mutation in solute carrier family 26 member 2 (SLC26A2), a gene...

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Bibliographic Details
Published in:American journal of medical genetics. Part A 2020-04, Vol.182 (4), p.735-739
Main Authors: Sato, Taisuke, Kojima, Takashi, Samura, Osamu, Kawaguchi, Satoshi, Nakamura, Akie, Nakajima, Masahiro, Tanuma‐Takahashi, Akiko, Nakabayashi, Kazuhiko, Hata, Kenichiro, Ikegawa, Shiro, Nishimura, Gen, Okamoto, Aikou, Yamada, Takahiro
Format: Article
Language:English
Subjects:
Achondrogenesis
Achondroplasia - genetics
Achondroplasia - pathology
Adult
Arginine
direct sequencing
Edema
Female
Fetuses
Glycine
Humans
Japan
Male
Mutation
Pedigree
Phenotype
Phenotypes
Point mutation
skeletal dysplasia
solute carrier family 26 member 2
Sulfate Transporters - genetics
whole‐exome sequencing
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Summary:We present two unrelated Japanese pedigrees with achondrogenesis type 1b (ACG1B), characterized by prenatally lethal fetal hydrops and severe micromelia. The affected members in these pedigrees carried a common homozygous missense point mutation in solute carrier family 26 member 2 (SLC26A2), a gene associated with ACG1B (NM_000112:c.1987G>A). This loss‐of‐function point mutation causes substitution of glycine 663 with arginine in a highly conserved loop domain of SLC26A2. Interestingly, only a few cases of this mutation have been registered in Japanese genomic databases, and there are no reports of this mutation in any major genomic databases outside Japan. Furthermore, we confirmed the presence of a homozygous stretch of approximately 75 kb surrounding the pathogenic variant. Our findings suggest that this missense point mutation in SLC26A2, which is likely the cause of the ACG1B phenotypes in these unrelated fetuses, is distributed exclusively in Japan.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.61469