Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies


Accogli A., Zaki M. S., Al-Owain M., Otaif M. Y., Jackson A., Argilli E., ...Daha Fazla

BRAIN COMMUNICATIONS, cilt.5, sa.5, 2023 (ESCI) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 5 Sayı: 5
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1093/braincomms/fcad222
  • Dergi Adı: BRAIN COMMUNICATIONS
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, Psycinfo, Directory of Open Access Journals
  • Anahtar Kelimeler: corpus callosum hypoplasia, ear-of-the-lynx sign, endoplasmic reticulum, LNPK, substantia nigra
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

LNPK encodes a conserved membrane protein that stabilizes the junctions of the tubular endoplasmic reticulum network playing crucial roles in diverse biological functions. Recently, homozygous variants in LNPK were shown to cause a neurodevelopmental disorder (OMIM#618090) in four patients displaying developmental delay, epilepsy and nonspecific brain malformations including corpus callosum hypoplasia and variable impairment of cerebellum. We sought to delineate the molecular and phenotypic spectrum of LNPK-related disorder. Exome or genome sequencing was carried out in 11 families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals, including review of previously reported patients. We identified 12 distinct homozygous loss-of-function variants in 16 individuals presenting with moderate to profound developmental delay, cognitive impairment, regression, refractory epilepsy and a recognizable neuroimaging pattern consisting of corpus callosum hypoplasia and signal alterations of the forceps minor ('ear-of-the-lynx' sign), variably associated with substantia nigra signal alterations, mild brain atrophy, short midbrain and cerebellar hypoplasia/atrophy. In summary, we define the core phenotype of LNPK-related disorder and expand the list of neurological disorders presenting with the 'ear-of-the-lynx' sign suggesting a possible common underlying mechanism related to endoplasmic reticulum-phagy dysfunction. In this study, Accogli et al. delineate the molecular and clinical spectrum of LNPK-related neurodevelopmental disorder with degenerative course, characterized by a recognizable neuroimaging pattern consisting of corpus callosum hypoplasia and signal alterations of the forceps minor ('ear-of-the-lynx' sign), suggesting a pathomechanism related to endoplasmic reticulum-phagy dysfunction. Graphical Abstract