A novel partial deletion of the TBL1XR1 gene detected using SNP array in a patient with motor delay, growth failure and Klinefelter syndrome.

INTRODUCTION: Co-existence pathogenic copy number variation with aneuploidy is a rare phenomenon. Whole TBL1XR1 gene deletions are described and associated with autosomal dominant intellectual development disorder-41 (#616944). However, the phenotypical expression of the TBL1XR1 partial deletion is poorly described. CASE PRESENTATION: We describe the case of a male, aged 18 months, who presented delayed motor development, gait disturbance, mild generalized hypotonia, minor dysmorphic features and growth failure, in addition to Klinefelter syndrome (KS). The single nucleotide polymorphism array revealed the de novo pathogenic interstitial deletion of chromosome 3q26.32 of 202 kb size that encompassed the first two exons of one relevant coding gene: TBL1XR1 (*608628). CONCLUSION: We report a male without clinical signs of KS and overlapped phenotypical features with another TBL1XR1 related disease: Pierpont syndrome (#602342). This patient extends the phenotypic spectrum of TBL1XR1 gene pathogenic variants.

Maternally inherited deletion encompassing the RTL1as and MEG8 genes of the human 14q32 imprinted region in a patient with a mild Kagami-Ogata syndrome phenotype.

Kagami-Ogata syndrome and Temple syndrome are imprinting disorders caused by the abnormal expression of genes in an imprinted cluster on chromosome 14q32. Here, we report a female with mild features of the Kagami-Ogata syndrome phenotype with polyhydramnios, neonatal hypotonia, feeding difficulties, abnormal foot morphology, patent foramen ovale, distal arthrogryposis, normal facial profile, and a bell-shaped thorax without coat hanger ribs. The single nucleotide polymorphism array revealed the interstitial deletion of chromosome 14q32.2-q32.31 (117 kb in size), involving the RTL1as and MEG8 genes, and other small nucleolar RNAs and microRNAs. The differentially methylated regions (DMRs) appeared unaltered. The RTL1as gene deletion and the normal methylation pattern of the MEG3 gene loci were confirmed by methylation-specific multiplex ligation-dependent probe amplification. Deletions of the 14q32 region without involving DMRs, and encompassing only the RTL1as and MEG8 genes, are poorly described in the literature. The mother's chromosomal microarray also confirmed the identical 14q32.2 deletion, although she presented a normal phenotype. The maternally inherited 14q32 deletion was responsible for Kagami-Ogata syndrome in our patient. It was not sufficient, however, to produce Temple syndrome or any other pathogenic phenotype in the patient's mother.