Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher–Neuhäuser Syndrome
Background: Boucher–Neuhäuser syndrome (BNS, MIM 215470) is a rare autosomal recessive syndrome caused by mutations in the PNPLA6 gene. Few BNS cases have been reported for functional validation at the RNA level. Herein, we report on the family of a 17-year-old girl with clinical characteristics of...
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.810537/full |
| _version_ | 1811189878183952384 |
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| author | Junyu He Xin Liu Liyi Liu Shaohao Zeng Shuanghong Shan Zhihong Liao |
| author_facet | Junyu He Xin Liu Liyi Liu Shaohao Zeng Shuanghong Shan Zhihong Liao |
| author_sort | Junyu He |
| collection | DOAJ |
| description | Background: Boucher–Neuhäuser syndrome (BNS, MIM 215470) is a rare autosomal recessive syndrome caused by mutations in the PNPLA6 gene. Few BNS cases have been reported for functional validation at the RNA level. Herein, we report on the family of a 17-year-old girl with clinical characteristics of BNS, genetic validation, and a systematic review of PNPLA6 variants related to BNS.Methods: Clinical data and blood samples were collected from the patient and their parents, and whole-exome sequencing was performed and confirmed by Sanger sequencing. RNA-sequencing (RNA-Seq) and quantitative RT-PCR (qRT-PCR) were performed, and the three-dimensional protein structures of the variants were predicted.Results: We report a 17-year-old female with progressive night blindness since the age of four, primary amenorrhea, and non-development of secondary sexual characteristics. Her impaired vision was diagnosed as retinal pigmentary degeneration of the retina. She had congenital hypogonadotropic hypogonadism (CHH) but no cerebellar ataxia at present. Two novel compound heterozygous variants (c.2241del/p.Met748TrpfsTer65 and c.2986A>G/p.Thr996Ala) of the PNPLA6 gene (NM_006702.4) were identified by whole-exome sequencing. The former variant was carried from her healthy father and has not been reported previously. The latter was inherited from her healthy mother and was noted in a report without functional studies. The RT-PCR results showed that the mRNA expression of PNPLA6 was lower in this patient and her father than in the control group. She was diagnosed with BNS. Both variants (c.2241del and c.2986A>G) were likely pathogenic according to the ACMG criteria. The novel variants in the PNPLA6 gene related to Boucher–Neuhäuser syndrome were summarized in this article.Conclusion: The possibility of Boucher–Neuhäuser syndrome should be considered when patients present with night blindness, impaired vision, and hypogonadotropic hypogonadism. Gene sequencing is currently the primary diagnostic method. Herein, novel compound heterozygous variants of PNPLA6 were identified in a BNS patient, and its function was verified at the RNA level. The PNPLA6 c.2241del variant is novel and potentially pathogenic, expanding the mutation spectrum in PNPLA6. |
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| spelling | doaj.art-e53e38d584cf4a14aa41a80b1dce1fc22022-12-22T04:17:51ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-02-011310.3389/fgene.2022.810537810537Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher–Neuhäuser SyndromeJunyu He0Xin Liu1Liyi Liu2Shaohao Zeng3Shuanghong Shan4Zhihong Liao5Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaAegicare Technology Co., Ltd., Shenzhen, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaBackground: Boucher–Neuhäuser syndrome (BNS, MIM 215470) is a rare autosomal recessive syndrome caused by mutations in the PNPLA6 gene. Few BNS cases have been reported for functional validation at the RNA level. Herein, we report on the family of a 17-year-old girl with clinical characteristics of BNS, genetic validation, and a systematic review of PNPLA6 variants related to BNS.Methods: Clinical data and blood samples were collected from the patient and their parents, and whole-exome sequencing was performed and confirmed by Sanger sequencing. RNA-sequencing (RNA-Seq) and quantitative RT-PCR (qRT-PCR) were performed, and the three-dimensional protein structures of the variants were predicted.Results: We report a 17-year-old female with progressive night blindness since the age of four, primary amenorrhea, and non-development of secondary sexual characteristics. Her impaired vision was diagnosed as retinal pigmentary degeneration of the retina. She had congenital hypogonadotropic hypogonadism (CHH) but no cerebellar ataxia at present. Two novel compound heterozygous variants (c.2241del/p.Met748TrpfsTer65 and c.2986A>G/p.Thr996Ala) of the PNPLA6 gene (NM_006702.4) were identified by whole-exome sequencing. The former variant was carried from her healthy father and has not been reported previously. The latter was inherited from her healthy mother and was noted in a report without functional studies. The RT-PCR results showed that the mRNA expression of PNPLA6 was lower in this patient and her father than in the control group. She was diagnosed with BNS. Both variants (c.2241del and c.2986A>G) were likely pathogenic according to the ACMG criteria. The novel variants in the PNPLA6 gene related to Boucher–Neuhäuser syndrome were summarized in this article.Conclusion: The possibility of Boucher–Neuhäuser syndrome should be considered when patients present with night blindness, impaired vision, and hypogonadotropic hypogonadism. Gene sequencing is currently the primary diagnostic method. Herein, novel compound heterozygous variants of PNPLA6 were identified in a BNS patient, and its function was verified at the RNA level. The PNPLA6 c.2241del variant is novel and potentially pathogenic, expanding the mutation spectrum in PNPLA6.https://www.frontiersin.org/articles/10.3389/fgene.2022.810537/fullBoucher–Neuhäuser syndromePNPLA6 genehypogonadotropic hypogonadismchorioretinal dystrophysequencing |
| spellingShingle | Junyu He Xin Liu Liyi Liu Shaohao Zeng Shuanghong Shan Zhihong Liao Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher–Neuhäuser Syndrome Frontiers in Genetics Boucher– Neuhäuser syndrome PNPLA6 gene hypogonadotropic hypogonadism chorioretinal dystrophy sequencing |
| title | Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher–Neuhäuser Syndrome |
| title_full | Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher–Neuhäuser Syndrome |
| title_fullStr | Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher–Neuhäuser Syndrome |
| title_full_unstemmed | Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher–Neuhäuser Syndrome |
| title_short | Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher–Neuhäuser Syndrome |
| title_sort | identification of novel compound heterozygous variants of the pnpla6 gene in boucher neuhauser syndrome |
| topic | Boucher– Neuhäuser syndrome PNPLA6 gene hypogonadotropic hypogonadism chorioretinal dystrophy sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.810537/full |
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