Siblings with MAN1B1-CDG Showing Novel Biochemical Profiles

Congenital disorders of glycosylation (CDG), inherited metabolic diseases caused by defects in glycosylation, are characterized by a high frequency of intellectual disability (ID) and various clinical manifestations. Two siblings with ID, dysmorphic features, and epilepsy were examined using mass sp...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nobuhiko Okamoto, Tatsuyuki Ohto, Takashi Enokizono, Yoshinao Wada, Tomohiro Kohmoto, Issei Imoto, Yoshimi Haga, Junichi Seino, Tadashi Suzuki
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	MAN1B1 intellectual disability congenital disorders of glycosylation early-onset epileptic encephalopathy mass spectrometry Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d8762ed4b28945f98a16c4990c2bea59
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d8762ed4b28945f98a16c4990c2bea59
record_format	dspace
spelling	oai:doaj.org-article:d8762ed4b28945f98a16c4990c2bea592021-11-25T17:11:40ZSiblings with MAN1B1-CDG Showing Novel Biochemical Profiles10.3390/cells101131172073-4409https://doaj.org/article/d8762ed4b28945f98a16c4990c2bea592021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3117https://doaj.org/toc/2073-4409Congenital disorders of glycosylation (CDG), inherited metabolic diseases caused by defects in glycosylation, are characterized by a high frequency of intellectual disability (ID) and various clinical manifestations. Two siblings with ID, dysmorphic features, and epilepsy were examined using mass spectrometry of serum transferrin, which revealed a CDG type 2 pattern. Whole-exome sequencing showed that both patients were homozygous for a novel pathogenic variant of <i>MAN1B1</i> (NM_016219.4:c.1837del) inherited from their healthy parents. We conducted a HPLC analysis of sialylated N-linked glycans released from total plasma proteins and characterized the α1,2-mannosidase I activity of the lymphocyte microsome fraction. The accumulation of monosialoglycans was observed in MAN1B1-deficient patients, indicating N-glycan-processing defects. The enzymatic activity of MAN1B1 was compromised in patient-derived lymphocytes. The present patients exhibited unique manifestations including early-onset epileptic encephalopathy and cerebral infarction. They also showed coagulation abnormalities and hypertransaminasemia. Neither sibling had truncal obesity, which is one of the characteristic features of MAN1B1-CDG.Nobuhiko OkamotoTatsuyuki OhtoTakashi EnokizonoYoshinao WadaTomohiro KohmotoIssei ImotoYoshimi HagaJunichi SeinoTadashi SuzukiMDPI AGarticleMAN1B1intellectual disabilitycongenital disorders of glycosylationearly-onset epileptic encephalopathymass spectrometryBiology (General)QH301-705.5ENCells, Vol 10, Iss 3117, p 3117 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MAN1B1 intellectual disability congenital disorders of glycosylation early-onset epileptic encephalopathy mass spectrometry Biology (General) QH301-705.5
spellingShingle	MAN1B1 intellectual disability congenital disorders of glycosylation early-onset epileptic encephalopathy mass spectrometry Biology (General) QH301-705.5 Nobuhiko Okamoto Tatsuyuki Ohto Takashi Enokizono Yoshinao Wada Tomohiro Kohmoto Issei Imoto Yoshimi Haga Junichi Seino Tadashi Suzuki Siblings with MAN1B1-CDG Showing Novel Biochemical Profiles
description	Congenital disorders of glycosylation (CDG), inherited metabolic diseases caused by defects in glycosylation, are characterized by a high frequency of intellectual disability (ID) and various clinical manifestations. Two siblings with ID, dysmorphic features, and epilepsy were examined using mass spectrometry of serum transferrin, which revealed a CDG type 2 pattern. Whole-exome sequencing showed that both patients were homozygous for a novel pathogenic variant of <i>MAN1B1</i> (NM_016219.4:c.1837del) inherited from their healthy parents. We conducted a HPLC analysis of sialylated N-linked glycans released from total plasma proteins and characterized the α1,2-mannosidase I activity of the lymphocyte microsome fraction. The accumulation of monosialoglycans was observed in MAN1B1-deficient patients, indicating N-glycan-processing defects. The enzymatic activity of MAN1B1 was compromised in patient-derived lymphocytes. The present patients exhibited unique manifestations including early-onset epileptic encephalopathy and cerebral infarction. They also showed coagulation abnormalities and hypertransaminasemia. Neither sibling had truncal obesity, which is one of the characteristic features of MAN1B1-CDG.
format	article
author	Nobuhiko Okamoto Tatsuyuki Ohto Takashi Enokizono Yoshinao Wada Tomohiro Kohmoto Issei Imoto Yoshimi Haga Junichi Seino Tadashi Suzuki
author_facet	Nobuhiko Okamoto Tatsuyuki Ohto Takashi Enokizono Yoshinao Wada Tomohiro Kohmoto Issei Imoto Yoshimi Haga Junichi Seino Tadashi Suzuki
author_sort	Nobuhiko Okamoto
title	Siblings with MAN1B1-CDG Showing Novel Biochemical Profiles
title_short	Siblings with MAN1B1-CDG Showing Novel Biochemical Profiles
title_full	Siblings with MAN1B1-CDG Showing Novel Biochemical Profiles
title_fullStr	Siblings with MAN1B1-CDG Showing Novel Biochemical Profiles
title_full_unstemmed	Siblings with MAN1B1-CDG Showing Novel Biochemical Profiles
title_sort	siblings with man1b1-cdg showing novel biochemical profiles
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d8762ed4b28945f98a16c4990c2bea59
work_keys_str_mv	AT nobuhikookamoto siblingswithman1b1cdgshowingnovelbiochemicalprofiles AT tatsuyukiohto siblingswithman1b1cdgshowingnovelbiochemicalprofiles AT takashienokizono siblingswithman1b1cdgshowingnovelbiochemicalprofiles AT yoshinaowada siblingswithman1b1cdgshowingnovelbiochemicalprofiles AT tomohirokohmoto siblingswithman1b1cdgshowingnovelbiochemicalprofiles AT isseiimoto siblingswithman1b1cdgshowingnovelbiochemicalprofiles AT yoshimihaga siblingswithman1b1cdgshowingnovelbiochemicalprofiles AT junichiseino siblingswithman1b1cdgshowingnovelbiochemicalprofiles AT tadashisuzuki siblingswithman1b1cdgshowingnovelbiochemicalprofiles
_version_	1718412682538778624

Siblings with MAN1B1-CDG Showing Novel Biochemical Profiles

Ejemplares similares