Schimke XLID syndrome results from a deletion in BCAP31.

A family with three affected males and a second family with a single affected male with intellectual disability, microcephaly, ophthalmoplegia, deafness, and Involuntary limb movements were reported by Schimke and Associates in 1984. The affected males with Schimke X-linked intellectual disability (XLID) syndrome (OMIM# 312840) had a similar facial appearance with deep-set eyes, downslanting palpebral fissures, hypotelorism, narrow nose and alae nasi, cupped ears and spacing of the teeth. Two mothers had mild hearing loss but no other manifestations of the disorder. The authors considered the disorder to be distinctive and likely X-linked. Whole genome sequencing in the single affected male available and the three carrier females from one of the families with Schimke XLID syndrome identified a 2 bp deletion in the BCAP31 gene. During the past decade, pathogenic alterations of the BCAP31 gene have been associated with deafness, dystonia, and central hypomyelination, an XLID condition given the eponym DDCH syndrome. A comparison of clinical findings in Schimke XLID syndrome and DDCH syndrome shows them to be the same clinical entity. The BCAP31 protein functions in endoplasmic reticulum-associated degradation to promote ubiquitination and destruction of misfolded proteins.

[1]  K. Yoshiura,et al.  Possible mitochondrial dysfunction in a patient with deafness, dystonia, and cerebral hypomyelination (DDCH) due to BCAP31 Mutation , 2020, Molecular genetics & genomic medicine.

[2]  T. de Ravel,et al.  BCAP31-related syndrome: The first de novo report. , 2020, European journal of medical genetics.

[3]  Hefen Sun,et al.  BCAP31 drives TNBC development by modulating ligand-independent EGFR trafficking and spontaneous EGFR phosphorylation , 2019, Theranostics.

[4]  B. Wang,et al.  BAP31 deficiency contributes to the formation of amyloid‐β plaques in Alzheimer's disease by reducing the stability of RTN3 , 2018, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[5]  R. Stevenson,et al.  X‐linked intellectual disability update 2017 , 2018, American journal of medical genetics. Part A.

[6]  Q. K. Tan,et al.  Novel pathogenic variants in FOXP3 in fetuses with echogenic bowel and skin desquamation identified by ultrasound , 2017, American journal of medical genetics. Part A.

[7]  N. Monfared,et al.  BCAP31‐associated encephalopathy and complex movement disorder mimicking mitochondrial encephalopathy , 2017, American journal of medical genetics. Part A.

[8]  B. Wang,et al.  BAP31 is involved in T cell activation through TCR signal pathways , 2017, Scientific Reports.

[9]  R. Mao,et al.  BCAP31 Mutation Causing a Syndrome of Congenital Dystonia, Facial Dysorphism and Central Hypomyelination Discovered Using Exome Sequencing , 2016, Movement disorders clinical practice.

[10]  H. Osaka,et al.  Genotype–phenotype correlation of contiguous gene deletions of SLC6A8, BCAP31 and ABCD1 , 2015, Clinical Genetics.

[11]  C. Ryu,et al.  B‐Cell Receptor‐Associated Protein 31 Regulates Human Embryonic Stem Cell Adhesion, Stemness, and Survival via Control of Epithelial Cell Adhesion Molecule , 2014, Stem cells.

[12]  G. Raymond,et al.  Distal Xq28 microdeletions: Clarification of the spectrum of contiguous gene deletions involving ABCD1, BCAP31, and SLC6A8 with a new case and review of the literature , 2014, American journal of medical genetics. Part A.

[13]  M. Lathrop,et al.  Mutations in BCAP31 cause a severe X-linked phenotype with deafness, dystonia, and central hypomyelination and disorganize the Golgi apparatus. , 2013, American journal of human genetics.

[14]  M. Mizuguchi,et al.  Contiguous ABCD1 DXS1357E deletion syndrome: Report of an autopsy case , 2013, Neuropathology : official journal of the Japanese Society of Neuropathology.

[15]  R. Stevenson,et al.  Atlas of X-Linked Intellectual Disability Syndromes , 2012 .

[16]  N. Matsumoto,et al.  Contiguous deletion of SLC6A8 and BAP31 in a patient with severe dystonia and sensorineural deafness. , 2012, Molecular genetics and metabolism.

[17]  C. Barlowe,et al.  Yet1p and Yet3p, the Yeast Homologs of BAP29 and BAP31, Interact with the Endoplasmic Reticulum Translocation Apparatus and Are Required for Inositol Prototrophy* , 2010, The Journal of Biological Chemistry.

[18]  B. Wang,et al.  BAP31 Interacts with Sec61 Translocons and Promotes Retrotranslocation of CFTRΔF508 via the Derlin-1 Complex , 2008, Cell.

[19]  David J Stephens,et al.  Bap31 is an itinerant protein that moves between the peripheral endoplasmic reticulum (ER) and a juxtanuclear compartment related to ER-associated Degradation. , 2008, Molecular biology of the cell.

[20]  A. Fulton,et al.  X-linked creatine transporter defect: A report on two unrelated boys with a severe clinical phenotype , 2006, Journal of Inherited Metabolic Disease.

[21]  H. Moser,et al.  Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E: a novel neonatal phenotype similar to peroxisomal biogenesis disorders. , 2002, American journal of human genetics.

[22]  M. Edidin,et al.  Selective export of MHC class I molecules from the ER after their dissociation from TAP. , 2000, Immunity.

[23]  W. Annaert,et al.  Export of Cellubrevin from the Endoplasmic Reticulum Is Controlled by BAP31 , 1997, The Journal of cell biology.

[24]  W. Horton,et al.  A new X-linked syndrome comprising progressive basal ganglion dysfunction, mental and growth retardation, external ophthalmoplegia, postnatal microcephaly and deafness. , 1984, American journal of medical genetics.