ABSTRACT
Distal 15q25.2 microdeletions have recently been reported as a copy number variation (CNV) locus for neurodevelopmental and neuropsychiatric disorders with variable outcome. In addition, more proximal microdeletions of 15q25.2 have been described as a susceptibility locus for cognitive deficits, congenital diaphragmatic hernia (CDH), and Diamond-Blackfan anaemia (DBA). We describe two patients with 15q25.2 deletion, one with the more distal deletion and the other with a deletion overlapping both the distal and proximal 15q25.2 deletions and compare them to the 18 so far reported patients with 15q25.2 deletions. We provide a characterization of the 15q25.2 microdeletions and contribute to the genotype-phenotype delineation for these two novel microdeletion syndromes.
Subject(s)
Genetic Loci , Abnormalities, Multiple/genetics , Abnormalities, Multiple/physiopathology , Anemia, Diamond-Blackfan/genetics , Anemia, Diamond-Blackfan/physiopathology , Child , Child, Preschool , Chromosome Deletion , Chromosomes, Human, Pair 15/genetics , Gene Deletion , Genetic Association Studies , Genotype , Germany , Hernia, Diaphragmatic/genetics , Hernia, Diaphragmatic/physiopathology , Hernias, Diaphragmatic, Congenital , Humans , In Situ Hybridization, Fluorescence , Male , Microarray Analysis , PhenotypeABSTRACT
AIM: A 6-month-old infant with severe hyporegenerative anaemia, muscular hypotonia and developmental delay is reported, and the metabolic, diagnostic and therapeutic implications of this case are discussed. RESULTS: Diagnostic work-up disclosed vitamin B12 depletion with an elevated excretion of methylmalonic acid (MMA), but a normal plasma total homocysteine. MRI showed fronto-temporal atrophy and a delay in myelinization. The boy's disease was attributable to a maternal atrophic gastritis. After initiation of vitamin B12 supplementation, he quickly recovered regarding haematopoiesis and MMA excretion. His neurological development completely normalized during 18 months of follow-up including assessment by Bayley scores. CONCLUSION: As the majority of reported patients with this acquired form of methylmalonic aciduria show a persistent neurological deficit, early diagnosis of this condition is mandatory and should include sensitive markers of vitamin B12 depletion, namely MMA formation and plasma homocysteine.
