Kobari Yasuko, Miyata Non, Takayama Jun, Saijo Naoya, Suzuki Tomohisa, Kure Shigeo, Kikuchi Atsuo, Tamiya Gen, Takizawa Takumi
Department of AI and Innovative Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan.
Mol Genet Genomic Med. 2025 Jun;13(6):e70112. doi: 10.1002/mgg3.70112.
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.
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.
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.
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.
伦茨 - 马耶夫斯基综合征（LMS）是一种罕见的遗传性疾病，其特征为骨硬化、智力残疾、特征性面容以及独特的颅面、牙齿、皮肤和远端肢体异常。编码磷脂酰丝氨酸（PS）合成酶之一PSS1的PTDSS1基因突变已被确定为LMS患者的致病原因。这些突变使PSS1对PS水平的反馈抑制不敏感。
对一名患有先天性皮肤松弛症的患者及其父母进行了全基因组测序（WGS）。分析了PTDSS1突变cDNA克隆中的PS合成酶活性，以评估功能改变。
一名5岁女孩出现先天性皮肤皱纹，最初被诊断为先天性皮肤松弛症。她患有双侧内耳发育不全、双侧低频听力损失、注意力缺陷多动障碍和轻度智力残疾。体格检查发现耳朵突出、额部隆起和牙齿排列不齐。通过WGS鉴定出PTDSS1基因中的一个新生杂合错义变体，c.284G>A（p.Arg95Gln）。功能分析表明PS合成酶活性增加，支持了该变体的致病性。
患者的皮肤松弛症和面部特征与LMS一致，尽管影像学检查结果未显示先前病例中报道的特征性硬化性骨发育异常。这一观察结果表明，LMS可能具有比先前认识到的更广泛的表型谱。
