Novel ALG12 variants and hydronephrosis in siblings with impaired N-glycosylation.
Brain Dev
; 43(9): 945-951, 2021 Oct.
Article
en En
| MEDLINE
| ID: mdl-34092405
ABSTRACT
BACKGROUND:
ALG12-CDG is a rare autosomal recessive type I congenital disorder of glycosylation (CDG) due to pathogenic variants in ALG12 which encodes the dolichyl-P-mannoseMan-7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase. Thirteen patients from unrelated 11 families have been reported, most of them result in broad multisystem manifestations with clinical variability. It is important to validate abnormal glycosylation to establish causal relationship. CASE REPORT Here, we report two siblings with novel compound heterozygous variants in ALG12 c.443T>C, p.(Leu148Pro) and c.412_413insCGT, p.(Gln137_Phe138insSer). Both patients showed global developmental delay, microcephaly, hypotonia, failure to thrive, facial dysmorphism, skeletal malformations and coagulation abnormalities, which are common in ALG12-CDG. In addition, one of our patients showed left hydronephrosis, which is a novel clinical feature in ALG12-CDG. Brain MRI showed hypoplasia of cerebrum, brain stem and cerebellar vermis in both patients. N-glycosylation defects of trypsin digested transferrin peptides were revealed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), and electrospray ionization MS verified the lack of N-glycans in transferrin.CONCLUSIONS:
The present study can add hydronephrosis to phenotypic spectrum of ALG12-CDG. Since the symptoms of ALG12-CDG are quite diverse, the combination of whole-exome sequencing and transferrin glycopeptide analysis with MS, can help diagnosis of ALG12-CDG.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trastornos Congénitos de Glicosilación
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Hidronefrosis
/
Manosiltransferasas
Tipo de estudio:
Diagnostic_studies
Límite:
Child
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Humans
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Male
Idioma:
En
Revista:
Brain Dev
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón