Murakami, Yoshiko, Baratang, Nissan, Raju, Praveen K., Knaus, Alexej, Ellard, Sian, Jones, Gabriela, Lace, Baiba ORCID: 0000-0001-5371-6756, Rousseau, Justine ORCID: 0000-0002-3554-2673, Ajeawung, Norbert Fonya, Kamei, Atsushi, Minase, Gaku, Akasaka, Manami, Araya, Nami, Koshimizu, Eriko, van den Ende, Jenneke, Erger, Florian ORCID: 0000-0002-2768-1702, Altmueller, Janine, Krumina, Zita, Strautmanis, Jurgis, Inashkina, Inna ORCID: 0000-0002-7560-797X, Stavusis, Janis, El-Gharbawy, Areeg, Sebastian, Jessica, Puri, Ratna Dua, Kulshrestha, Samarth ORCID: 0000-0001-6749-3661, Verma, Ishwar C., Maier, Esther M., Haack, Tobias B., Israni, Anil, Baptista, Julia, Gunning, Adam, Rosenfeld, Jill A., Liu, Pengfei, Joosten, Marieke, Rocha, Maria Eugenia, Hashem, Mais O., Aldhalaan, Hesham M., Alkuraya, Fowzan S., Miyatake, Satoko, Matsumoto, Naomichi, Krawitz, Peter M., Rossignol, Elsa, Kinoshita, Taroh and Campeau, Philippe M. (2019). Mutations in PIGB Cause an Inherited GPI Biosynthesis Defect with an Axonal Neuropathy and Metabolic Abnormality in Severe Cases. Am. J. Hum. Genet., 105 (2). S. 384 - 395. CAMBRIDGE: CELL PRESS. ISSN 1537-6605

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Abstract

Proteins anchored to the cell surface via glycosylphosphatidylinositol (GPI) play various key roles in the human body, particularly in development and neurogenesis. As such, many developmental disorders are caused by mutations in genes involved in the GPI biosynthesis and remodeling pathway. We describe ten unrelated families with bi-allelic mutations in PIGB, a gene that encodes phosphatidy-linositol glycan class B, which transfers the third mannose to the GPI. Ten different PIGB variants were found in these individuals. Flow cytometric analysis of blood cells and fibroblasts from the affected individuals showed decreased cell surface presence of GPI-anchored proteins. Most of the affected individuals have global developmental and/or intellectual delay, all had seizures, two had polymicrogyria, and four had a peripheral neuropathy. Eight children passed away before four years old. Two of them had a clinical diagnosis of DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures), a condition that includes sensorineural deafness, shortened terminal phalanges with small finger and toenails, intellectual disability, and seizures; this condition overlaps with the severe phenotypes associated with inherited GPI deficiency. Most individuals tested showed elevated alkaline phosphatase, which is a characteristic of the inherited GPI deficiency but not DOORS syndrome. It is notable that two severely affected individuals showed 2-oxoglutaric aciduria, which can be seen in DOORS syndrome, suggesting that severe cases of inherited GPI deficiency and DOORS syndrome might share some molecular pathway disruptions.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Murakami, YoshikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baratang, NissanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raju, Praveen K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knaus, AlexejUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ellard, SianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jones, GabrielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lace, BaibaUNSPECIFIEDorcid.org/0000-0001-5371-6756UNSPECIFIED
Rousseau, JustineUNSPECIFIEDorcid.org/0000-0002-3554-2673UNSPECIFIED
Ajeawung, Norbert FonyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kamei, AtsushiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Minase, GakuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Akasaka, ManamiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Araya, NamiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koshimizu, ErikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van den Ende, JennekeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erger, FlorianUNSPECIFIEDorcid.org/0000-0002-2768-1702UNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krumina, ZitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strautmanis, JurgisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Inashkina, InnaUNSPECIFIEDorcid.org/0000-0002-7560-797XUNSPECIFIED
Stavusis, JanisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
El-Gharbawy, AreegUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sebastian, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puri, Ratna DuaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kulshrestha, SamarthUNSPECIFIEDorcid.org/0000-0001-6749-3661UNSPECIFIED
Verma, Ishwar C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, Esther M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haack, Tobias B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Israni, AnilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baptista, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gunning, AdamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenfeld, Jill A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, PengfeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Joosten, MariekeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rocha, Maria EugeniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hashem, Mais O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aldhalaan, Hesham M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alkuraya, Fowzan S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miyatake, SatokoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matsumoto, NaomichiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krawitz, Peter M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rossignol, ElsaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kinoshita, TarohUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campeau, Philippe M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-145981
DOI: 10.1016/j.ajhg.2019.05.019
Journal or Publication Title: Am. J. Hum. Genet.
Volume: 105
Number: 2
Page Range: S. 384 - 395
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1537-6605
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DOOR SYNDROME; MENTAL-RETARDATION; PROTEIN; DEFICIENCY; CD59Multiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14598

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