A maternally inherited 8.05 Mb Xq21 deletion associated with Choroideremia, deafness, and mental retardation syndrome in a male patient

Abstract

BackgroundDeletions in Xq21 cause various congenital defects in males including choroideremia, deafness and mental retardation, depending on their size and gene content. Until now only a limited number of patients with Xq21 deletions has been reported.Case presentationHere we describe a 17-year-old male with choroideremia, deafness, and mental retardation syndrome. Using SNP arrays, an 8.05 Mb deletion in Xq21 was identified inherited from the apparently healthy mother. The deleted region harbors 12 OMIM genes, of which POU3F4, CHM, and ZNF711 might have contributed to the patient’s phenotype including hearing loss, poor vision, and intellectual disability. Moreover, the patient’s mother exhibits a normal phenotype while carrying the same deletion, which is often observed in previous studies on female carriers in families with this syndrome.ConclusionsOur study confirms the causative effect between the Xq21 deletion in males and choroideremia, deafness and mental retardation.

A novel mutation of X‐linked recessive deafness gene POU3F4 in a boy with congenital deafness

“…The specific phenotype depends on the size of CNVs and the content of pathogenic genes, mainly including DFNX2, attention deficit, mental retardation, and choroidal hemorrhage. 18 , 19 , 20 , 21 , 22 Although the deletion range in our case also covered other genes, the patient did not present other specific phenotypes, and there was no clear evidence of pathogenicity in the other genes at present, so syndromic hearing impairment was ruled out in our patient. However, it cannot be ruled out that the proteins encoded by other genes may interact with the mutated POU3F4 gene and produce functional changes associated with the observed phenotypes, which need to be further identified by genome‐wide analysis.…”

“…The specific phenotype depends on the size of CNVs and the content of pathogenic genes, mainly including DFNX2, attention deficit, mental retardation, and choroidal hemorrhage. [18][19][20][21][22] Although the deletion range in our case also covered other genes, the patient did not present other specific phenotypes, and there was no clear evidence of pathogenicity in the other genes at present, so syndromic hearing impairment was ruled out in our patient.…”

Xq21.1q21.31 Duplication in Two Male Siblings

“…Hemizygous loss-of-function variants in ZNF711 are associated with mild to moderate intellectual disability in males, with autistic features and mild facial dysmorphisms noted in some patients [Tarpey et al, 2009;Van der Werf et al, 2017]. Loss of ZNF711 is also considered to be causative of the intellectual disability seen in males with Xq21 deletions [Liang et al, 2017]. The duplication of ZNF711 observed in the current patients could potentially lead to dysregulation of ZNF711 target gene expression during development, which could contribute to the neurodevelopmental and behavioural features in patients with Xq21 duplications.…”

CHM mutation spectrum and disease: An update at the time of human therapeutic trials

“…Therefore, it is unclear whether the same or different mutations are underlying the disease. Larger deletions encompassing flanking genes have been described and were often associated with syndromic features, as contiguous gene syndromes, including orofacial clefting, mental and motor retardation, and hearing loss (Iossa et al, 2015; Liang et al, 2017; Poloschek et al, 2008; Rush & Schaefer, 2010; Table S3.1). In addition, three different translocations in female carriers have been identified (Bokhoven et al, 1994; Cremers et al, 1990; García‐Hoyos et al, 2005; Garcia‐Hoyos et al, 2008; Lorda‐Sanchez et al, 2000).…”