Novel LNPK variant causes progressive cerebral atrophy: Expanding the clinical phenotype

Abstract

The biallelic variations of the LNPK gene are associated with the "neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum" phenotype [MIM:618090] in the Online Mendelian Inheritance In Men database, and so far, two families have been identified in the literature. A third family with novel clinical features, who bears a novel variant in LNPK (NM_030650.3: c.770delA, p.D257fs*31) is described in the present study. The coexistence of psychomotor regression and neurodegeneration in brain magnetic resonance imaging was found for the first time in the present study, thanks to the long-term follow-up data on the case, which contributed to the phenotypic and mutation spectrum by means of the novel variation.

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

“…Families 13 and 14 have been reported by Breuss et al . 9 and Türkyılmaz et al ., 10 respectively. ASM, antiseizure medications; AOO, of onset; atyp, atypical; Bil., bilateral; CCH, corpus callosum hypoplasia; GDD, global developmental delay; DTR, deep tendon reflexes; F, female; FP, frontoparietal; hom, homozygous; myo, myoclonic; TC, tonic–clonic; ID, intellectual disability; IVH, inferior vermis hypoplasia; m, months; OFC, occipital frontal circumference; ONA, optic nerve atrophy; M, male; NA, not available; SA, signal alterations; SDS, standard deviations; WMVL, white matter volume loss; y, years.…”

“…Brain MRI studies were available for review in 18 patients (14 from the present cohort and 4 from previous publications 9 , 10 ; mean age at MRI: 4.6 years, range 1–14 years) ( Supplementary Fig. 1 ).…”

“…Sixteen previously unreported patients from 12 families of different ancestries (Egyptian, Iranian, Turkish, Saudi Arabian, Afghan, Pakistani and British) as well as additional follow-up data from four patients reported from three families (Egyptian, Pakistani and Turkish) 9 , 10 were included in this study after obtaining written informed consent ( Fig. 1A ).…”

“…Clinical data were collected using standardized pro forma from around 10 different hospitals and clinics, for all individuals. Brain magnetic resonance imaging (MRI) of these and of the previously reported patients 9 , 10 were reviewed by an experienced neuroradiologist (M.S.). Exome sequencing (ES) or genome sequencing (Family 2) was performed in probands in the respective collaborating centres using slightly different analysis platforms according to the BWA/GATK-based pipelines.…”

“…Recently, three homozygous loss-of-function (LoF) variants in LNPK were shown to cause a neurodevelopmental disorder (OMIM#618090) in four patients displaying global developmental delay (GDD)/intellectual disability (ID), epilepsy, corpus callosum hypoplasia and variable impairment of cerebellar development. 9 , 10 …”