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This study presents a clinical report of the Finnish chromosome t(18q; 10p) translocation family with an overview of eight other selected immunoglobulin A (IgA)-deficient 18q deletion (18q−) patients from seven published articles. The family members show features common to 18q− syndrome such as mental retardation, multiple facial dysmorphism, foot/hand deformities, abnormal myelination of brain white matter, and a spectrum of immunological/infectious disorders including IgA deficiency (IgAD). Genotype–phenotype correlation study of the unbalanced t(18q−; 10p+) translocation family members and other 18q− syndrome reports led to definition of a potential susceptibility gene locus for IgAD at distal region of 18q22.3–q23 between markers D18S812–18qter. The haplo-insufficiency of the 18q22.3–q23 gene region is suggested to be a cause of the IgAD phenotype in 18q− individuals. This 7 Mb IgAD critical region shows significant association with susceptibility region for celiac disease that is frequently connected to IgAD. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Allo-SCT in a patient with CRMCC with aplastic anemia using a reduced intensity conditioning regimen," in the 2012 issue.

Cerebral folate transport deficiency is an inherited brain-specific folate transport defect that is caused by mutations in the folate receptor 1 gene coding for folate receptor alpha (FRα). This genetic defect gives rise to a progressive neurological disorder with late infantile onset. We screened 72 children with low 5-methyltetrahydrofolate concentrations in the cerebrospinal fluid and neurological symptoms that developed after infancy. We identified nucleotide alterations in the folate receptor 1 gene in 10 individuals who shared developmental regression, ataxia, profound cerebral hypomyelination and cerebellar atrophy. We found four novel pathogenic alleles, one splice mutation and three missense mutations. Heterologous expression of the missense mutations, including previously described mutants, revealed minor decrease in protein expression but loss of cell surface localization, mistargeting to intracellular compartments and thus absence of cellular binding of folic acid. These results explain the functional loss of folate receptor alpha for all detected folate receptor 1 mutations. Three individuals presenting a milder clinical phenotype revealed very similar biochemical and brain imaging data but partially shared pathogenic alleles with more severely affected patients. Thus, our studies suggest that different clinical severities do not necessarily correlate with residual function of folate receptor alpha mutants and indicate that additional factors contribute to the clinical phenotype in cerebral folate transport deficiency. [ABSTRACT FROM AUTHOR]

Purpose To describe retinal abnormalities other than Coats' reaction in 4 of 6 Finnish patients with CRMCC, also known as Coats' plus. Methods An observational series of genotyped children imaged with RetCam. The children (5 girls, 1 boy) were born prematurely on gestational week 30‐39 and were small for date with birth weights from 770 to 2170 g. Four are alive at age 4‐22 y and two have died at age 6 and 18 y. Results Of the 6 children, 2 presented with bilateral, asymmetric Coats' reaction at age 7 and 11 months. The more advanced eye had an exudative retinal detachment (RD). Three children had retinal angiomas without exudation, accompanied with preretinal and vitreous bleedings, and abnormally running circular vascular loops at age 2‐11 months. In two of the latter, traction RD developed. Regardless of the phenotype, the retina peripheral to the vascular anomalies was avascular but without ROP changes. One patient did not have clinically visible retinal vascular anomalies. All patients with retinal changes had the common c.1994T>G [p.Val665Gly] mutation, three with c.2831delC [p.Pro944Leufs*7] and one each with c.3583C>T [p.Arg1195*] and c.3425_3426delTCinsAT [p.Leu1142His] mutations. The genotype did not predict the phenotype. The patient without retinal changes had c.680C>T [p.Ala227Val] mutation with c.2831delC [p.Pro944Leufs*7]. Other Finnish patients with the latter ccombination have had retinal changes since early childhood. Conclusion It is important to appreciate that CRMCC can present with retinal phenotypes other than Coats' reaction, and a minority may not have any visible retinal changes. Also angiomas call for neuroimaging to identify brain cysts and calcifications which characterize CRMCC [ABSTRACT FROM AUTHOR]