A Japanese Case of Lenz‐Majewski Syndrome With a Novel PTDSS1 Variant
ABSTRACT Background Lenz‐Majewski syndrome (LMS) is a rare genetic disorder characterized by osteosclerosis, intellectual disability, characteristic facies, and distinct craniofacial, dental, cutaneous, and distal‐limb anomalies. Mutations in the PTDSS1 gene, which encodes one of the phosphatidylser...
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Wiley
2025-06-01
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| Online Access: | https://doi.org/10.1002/mgg3.70112 |
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| author | Yasuko Kobari Non Miyata Jun Takayama Naoya Saijo Tomohisa Suzuki Shigeo Kure Atsuo Kikuchi Gen Tamiya Takumi Takizawa |
| author_facet | Yasuko Kobari Non Miyata Jun Takayama Naoya Saijo Tomohisa Suzuki Shigeo Kure Atsuo Kikuchi Gen Tamiya Takumi Takizawa |
| author_sort | Yasuko Kobari |
| collection | DOAJ |
| description | ABSTRACT Background Lenz‐Majewski syndrome (LMS) is a rare genetic disorder characterized by osteosclerosis, intellectual disability, characteristic facies, and distinct craniofacial, dental, cutaneous, and distal‐limb anomalies. Mutations in the PTDSS1 gene, which encodes one of the phosphatidylserines (PS) synthase enzymes, PSS1, have been identified as causative in LMS patients. These mutations make PSS1 insensitive to feedback inhibition by PS levels. Methods Whole genome sequence (WGS) was performed on a patient with congenital cutis laxa and her parents. PS synthase activity was analyzed in PTDSS1 mutant cDNA clones to evaluate functional alterations. Results A 5‐year‐old girl presented with congenital skin wrinkles and was initially diagnosed with congenital cutis laxa. She had bilateral inner ear hypoplasia, bilateral low‐frequency hearing loss, attention‐deficit/hyperactivity disorder, and mild intellectual disability. Physical examination revealed protruding ears, frontal bossing, and dental malalignment. A de novo heterozygous missense variant in the PTDSS1 gene, c.284G>A (p. Arg95Gln) was identified by WGS. Functional analysis indicated increased PS synthase activity, supporting the pathogenicity of this variant. Conclusions The patient's cutis laxa and facial features were consistent with LMS, though radiographic findings did not reveal the characteristic sclerosing bone dysplasia reported in previous cases. This observation suggests that LMS may have a broader phenotypic spectrum than previously recognized. |
| format | Article |
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| institution | DOAJ |
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| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-d0ba62b775fd4d03922f0155bd7e24ef2025-08-20T03:23:56ZengWileyMolecular Genetics & Genomic Medicine2324-92692025-06-01136n/an/a10.1002/mgg3.70112A Japanese Case of Lenz‐Majewski Syndrome With a Novel PTDSS1 VariantYasuko Kobari0Non Miyata1Jun Takayama2Naoya Saijo3Tomohisa Suzuki4Shigeo Kure5Atsuo Kikuchi6Gen Tamiya7Takumi Takizawa8Department of AI and Innovative Medicine Tohoku University Graduate School of Medicine Sendai JapanDepartment of Biochemistry and Cell Biology National Institute of Infectious Diseases Tokyo JapanDepartment of AI and Innovative Medicine Tohoku University Graduate School of Medicine Sendai JapanDepartment of Pediatrics Tohoku University Graduate School of Medicine Sendai JapanDepartment of Rare Disease Genomics Tohoku University Graduate School of Medicine Sendai JapanDepartment of Rare Disease Genomics Tohoku University Graduate School of Medicine Sendai JapanDepartment of Rare Disease Genomics Tohoku University Graduate School of Medicine Sendai JapanDepartment of AI and Innovative Medicine Tohoku University Graduate School of Medicine Sendai JapanDepartment of Pediatrics Gunma University Graduate School of Medicine Maebashi JapanABSTRACT Background Lenz‐Majewski syndrome (LMS) is a rare genetic disorder characterized by osteosclerosis, intellectual disability, characteristic facies, and distinct craniofacial, dental, cutaneous, and distal‐limb anomalies. Mutations in the PTDSS1 gene, which encodes one of the phosphatidylserines (PS) synthase enzymes, PSS1, have been identified as causative in LMS patients. These mutations make PSS1 insensitive to feedback inhibition by PS levels. Methods Whole genome sequence (WGS) was performed on a patient with congenital cutis laxa and her parents. PS synthase activity was analyzed in PTDSS1 mutant cDNA clones to evaluate functional alterations. Results A 5‐year‐old girl presented with congenital skin wrinkles and was initially diagnosed with congenital cutis laxa. She had bilateral inner ear hypoplasia, bilateral low‐frequency hearing loss, attention‐deficit/hyperactivity disorder, and mild intellectual disability. Physical examination revealed protruding ears, frontal bossing, and dental malalignment. A de novo heterozygous missense variant in the PTDSS1 gene, c.284G>A (p. Arg95Gln) was identified by WGS. Functional analysis indicated increased PS synthase activity, supporting the pathogenicity of this variant. Conclusions The patient's cutis laxa and facial features were consistent with LMS, though radiographic findings did not reveal the characteristic sclerosing bone dysplasia reported in previous cases. This observation suggests that LMS may have a broader phenotypic spectrum than previously recognized.https://doi.org/10.1002/mgg3.70112congenital cutis laxaLenz‐Majewski syndromephenotypic spectrumPTDSS1 gene |
| spellingShingle | Yasuko Kobari Non Miyata Jun Takayama Naoya Saijo Tomohisa Suzuki Shigeo Kure Atsuo Kikuchi Gen Tamiya Takumi Takizawa A Japanese Case of Lenz‐Majewski Syndrome With a Novel PTDSS1 Variant Molecular Genetics & Genomic Medicine congenital cutis laxa Lenz‐Majewski syndrome phenotypic spectrum PTDSS1 gene |
| title | A Japanese Case of Lenz‐Majewski Syndrome With a Novel PTDSS1 Variant |
| title_full | A Japanese Case of Lenz‐Majewski Syndrome With a Novel PTDSS1 Variant |
| title_fullStr | A Japanese Case of Lenz‐Majewski Syndrome With a Novel PTDSS1 Variant |
| title_full_unstemmed | A Japanese Case of Lenz‐Majewski Syndrome With a Novel PTDSS1 Variant |
| title_short | A Japanese Case of Lenz‐Majewski Syndrome With a Novel PTDSS1 Variant |
| title_sort | japanese case of lenz majewski syndrome with a novel ptdss1 variant |
| topic | congenital cutis laxa Lenz‐Majewski syndrome phenotypic spectrum PTDSS1 gene |
| url | https://doi.org/10.1002/mgg3.70112 |
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