مورد إلكتروني
Linear Diagnostic Procedure Elicited by Clinical Genetics and Validated by mRNA Analysis in Neuronal Ceroid Lipofuscinosis 7 Associated with a Novel Non-Canonical Splice Site Variant in MFSD8
| العنوان: | Linear Diagnostic Procedure Elicited by Clinical Genetics and Validated by mRNA Analysis in Neuronal Ceroid Lipofuscinosis 7 Associated with a Novel Non-Canonical Splice Site Variant in MFSD8 |
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| بيانات النشر: | MDPI 2023 |
| تفاصيل مُضافة: | Pasquetti, Domizia Marangi, Giuseppe Orteschi, D. Carapelle, Marina L'Erario, Federica Francesca Venditti, Romina Maietta, Sabrina Battaglia, Domenica Immacolata Contaldo, Ilaria Veredice, Chiara Zollino, Marcella Pasquetti D. Marangi G. (ORCID:0000-0002-6898-8882) Carapelle M. L'Erario F. F. Venditti R. Maietta S. Battaglia D. I. (ORCID:0000-0003-0491-4021) Contaldo I. Veredice C. Zollino M. (ORCID:0000-0003-4871-9519) |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Neuronal ceroid lipofuscinoses (CNL) are lysosomal storage diseases that represent the most common cause of dementia in children. To date, 13 autosomal recessive (AR) and 1 autosomal dominant (AD) gene have been characterized. Biallelic variants in MFSD8 cause CLN7 type, with nearly 50 pathogenic variants, mainly truncating and missense, reported so far. Splice site variants require functional validation. We detected a novel homozygous non-canonical splice-site variant in MFSD8 in a 5-year-old girl who presented with progressive neurocognitive impairment and microcephaly. The diagnostic procedure was elicited by clinical genetics first, and then confirmed by cDNA sequencing and brain imaging. Inferred by the common geographic origin of the parents, an autosomal recessive inheritance was hypothesized, and SNP-array was performed as the first-line genetic test. Only three AR genes lying within the observed 24 Mb regions of homozygosity were consistent with the clinical phenotype, including EXOSC9, SPATA5 and MFSD8. The cerebral and cerebellar atrophy detected in the meantime by MRI, along with the suspicion of accumulation of ceroid lipopigment in neurons, prompted us to perform targeted MFSD8 sequencing. Following the detection of a splice site variant of uncertain significance, skipping of exon 8 was demonstrated by cDNA sequencing, and the variant was redefined as pathogenic. |
| مصطلحات الفهرس: | clinical genetics, CNL7, MFSD8, mRNA, neurodevelopmental disorders, Settore MED/03 - GENETICA MEDICA, info:eu-repo/semantics/article |
| URL: | info:eu-repo/semantics/altIdentifier/pmid/36833170 info:eu-repo/semantics/altIdentifier/wos/WOS:000944893600001 volume:14 issue:2 firstpage:245 lastpage:N/A issueyear:2023 journal:GENES |
| الإتاحة: | Open access content. Open access content |
| ملاحظة: | English |
| أرقام أخرى: | SYC oai:publicatt.unicatt.it:10807/232270 10.3390/genes14020245 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85148906304 1382659916 |
| المصدر المساهم: | UNIV CATTOLICA DEL SACRO CUORE From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1382659916 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |