Lenz-Majewski syndrome: Report of a case with novel mutation in PTDSS1 gene

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, of the 14 living patients, five were at least 17 years or older at the time of publication. (Piard et al, ; Sousa et al, ; Tamhankar et al, ; Whyte et al, ).…”

Section: Discussionmentioning

confidence: 99%

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Lenz–Majewski syndrome in a patient from Egypt

Afifi

Abdel‐Hamid

Mehrez

et al. 2019

“…Gain of function mutations in PTDSS1 underlie LMS, which is an extremely rare syndrome with only 16 sporadic cases reported in the literature between 1969 and 2015 (Lenz & Majewski, 1974; Majewski, 2000; Sousa et al, 2014; Tamhankar et al, 2015; Whyte et al, 2015). Clinical features of LMS include craniotubular hyperostosis, loose skin, progeroid appearance, marked growth failure, and moderate to severe intellectual disability.…”

Section: Discussionmentioning

confidence: 99%

“…The p.Leu265Pro mutation corresponds to patient 1 in this report, while patient 3 in this report has c.806C>T; (p.Pro269Leu) resulting in a different amino acid substitution at the same Pro269 position to another LMS patient reported by Sousa et al (2014). Since then, two further LMS patients have been described, with mutations in exon 7 (Tamhankar et al, 2015; Whyte et al, 2015). This means that LMS is a very rare disease with our description here of the novel c.284G>T; (p.Arg95Leu), and c.806C>T; (p.Pro269Leu) PTDSS1 mutation representing only the eighth and ninth patients with confirmed molecular diagnoses reported so far.…”

Section: Discussionmentioning

confidence: 99%

Cutis laxa and excessive bone growth due to de novo mutations in PTDSS1

Piard

Lespinasse

Vlčková

et al. 2018

The cutis laxa syndromes are multisystem disorders that share loose redundant inelastic and wrinkled skin as a common hallmark clinical feature. The underlying molecular defects are heterogeneous and 13 different genes have been involved until now, all of them being implicated in elastic fiber assembly. We provide here molecular and clinical characterization of three unrelated patients with a very rare phenotype associating cutis laxa, facial dysmorphism, severe growth retardation, hyperostotic skeletal dysplasia, and intellectual disability. This disorder called Lenz–Majewski syndrome (LMS) is associated with gain of function mutations in PTDSS1, encoding an enzyme involved in phospholipid biosynthesis. This report illustrates that LMS is an unequivocal cutis laxa syndrome and expands the clinical and molecular spectrum of this group of disorders. In the neonatal period, brachydactyly and facial dysmorphism are two early distinctive signs, later followed by intellectual disability and hyperostotic skeletal dysplasia with severe dwarfism allowing differentiation of this condition from other cutis laxa phenotypes. Further studies are needed to understand the link between PTDSS1 and extra cellular matrix assembly.

De novo loss‐of‐function variant in PTDSS1 is associated with developmental delay

Gracie

Sengupta

Ferreira

et al. 2022

Heterozygous de novo missense pathogenic variants in PTDSS1 that result in gain-offunction of phosphatidylserine synthase 1 are associated with Lenz-Majewski hyperostotic dwarfism (LMHD). We identified the novel heterozygous de novo variant p.(Leu137Phe) in PTDSS1 in a child with mild-to-moderate developmental delay.Skeletal survey revealed no evidence of LMHD in this patient. Functional assessment of the p.Leu137Phe variant was performed by overexpressing the mutant protein into HEK293 cells. Following C 14 -serine labeling and TLC analysis of lipids, we observed that the p.(Leu137Phe) variant displayed no catalytic activity compared to the wild-type enzyme. We conclude that p.(Leu137Phe) variant has decreased enzymatic activity and that is likely to be the etiology of the patient's symptoms given the gene's constraint in the population. This is the first report of the clinical phenotype seen in an individual with a heterozygous loss-of-function variant in PTDSS1. This phenotype is distinct from LMHD, which results from gain-of-function pathogenic variants in the same gene. Evaluation of the neurodevelopmental phenotype of additional individuals with loss-of-function variants in PTDSS1 is indicated to determine the spectrum of associated phenotypes.