Identification of novel SNORD118 mutations in seven patients with leukoencephalopathy with brain calcifications and cysts

Abstract

Biallelic SNORD118 mutations were exclusively found in most unrelated families with LCC.

Leukoencephalopathy, Intracranial Calcifications, Cysts, and SNORD118 Mutation (Labrune Syndrome) with Obstructive Hydrocephalus

“…Histopathology of a biopsy of the cyst wall and calcified regions showed non-specific changes with no evidence of malignancy Genetic testing revealed an n.72A>G and an n.*10G>T biallelic variants in SNORD118 inherited from his carrier parents (See supplementary material for genetic M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPTtesting and electropherogram). Both variants have been previously described in other families affected by LCC 2,3. To our knowledge, we report the first case of a child with LCC (Labrune syndrome) with infra and supra tentorial calcifications and cyst with obstructive hydrocephalus that required neurosurgical intervention.…”

Longitudinal clinical and neuro-radiological findings in a patient with leukoencephalopathy with brain calcifications and cysts (Labrune syndrome)

“…Jenkinson et al [2] identified biallelic SNORD118 sequence variants throughout their cohort of 40 radiologically stereotyped European patients belonging to 33 families. Iwama et al [3] identified biallelic SNORD118 variants in 7 out of 8 of Japanese patients. Our patient exhibited the biallelic SNORD118 variants c.38C > G and c.116G > C. c.116G > C is a novel variant, but c.38C > G was documented in 1 Italian patient in Jenkinson et al’s study [2] and 6 Japanese patients in Iwama et al’s study [3] , which suggests that it may be relatively common in Japanese patients but rare in European patients.…”

“…Iwama et al [3] identified biallelic SNORD118 variants in 7 out of 8 of Japanese patients. Our patient exhibited the biallelic SNORD118 variants c.38C > G and c.116G > C. c.116G > C is a novel variant, but c.38C > G was documented in 1 Italian patient in Jenkinson et al’s study [2] and 6 Japanese patients in Iwama et al’s study [3] , which suggests that it may be relatively common in Japanese patients but rare in European patients. The relationships between individual mutations and clinical presentations remain unknown [2] , [3] .…”

“…Leukoencephalopathy with brain calcifications and cysts (LCC), also known as Labrune syndrome, is a neuro-radiologically characterised neurodegenerative genetic disorder [1] , [2] , [3] . Patients with LCC may present with mental retardation, convulsions, corticospinal tract and extrapyramidal signs, movement disorders, and cerebellar ataxia without extracranial abnormalities such as retinal vascular abnormalities [2] , [3] , [4] . However, these symptoms and signs are not LCC-specific, their presence and timing varies [2] , [3] , [4] , and their temporal development remains poorly understood [2] , [3] , [4] .…”

“…Patients with LCC may present with mental retardation, convulsions, corticospinal tract and extrapyramidal signs, movement disorders, and cerebellar ataxia without extracranial abnormalities such as retinal vascular abnormalities [2] , [3] , [4] . However, these symptoms and signs are not LCC-specific, their presence and timing varies [2] , [3] , [4] , and their temporal development remains poorly understood [2] , [3] , [4] . Jenkinson et al [2] recently identified LCC-related mutations in the gene encoding the box C/D small nucleolar RNA U8 ( SNORD118) , thus indicating that LCC may represent a novel ribosomopathy.…”