The emerging 3q13.31 microdeletion syndrome appears to encompass diverse neurodevelopmental conditions. However, the 3q13.31 deletion is rare and few adult cases have yet been reported. We examined a ...cohort with schizophrenia (n = 459) and adult control subjects (n = 26,826) using high-resolution microarray technology for deletions and duplications at the 3q13.31 locus.
We report on the extended adult phenotype associated with a 3q13.31 microdeletion in a 41-year-old male proband with schizophrenia and a nonverbal learning disability. He was noted to have a speech impairment, delayed motor skills, and other features consistent with the 3q13.31 microdeletion syndrome. The 2.06 Mb deletion overlapped two microRNAs and seven RefSeq genes, including GAP43, LSAMP, DRD3, and ZBTB20. No overlapping 3q13.31 deletions or duplications were identified in control subjects.
Later-onset conditions like schizophrenia are increasingly associated with rare copy number variations and associated genomic disorders like the 3q13.31 microdeletion syndrome. Detailed phenotype information across the lifespan facilitates genotype-phenotype correlations, accurate genetic counselling, and anticipatory care.
Conotruncal heart anomalies (CTDs) are particularly prevalent congenital heart diseases (CHD) in Hong Kong. We surveyed large (>500 kb), rare (<1% frequency in controls) copy-number variations (CNVs) ...in Chinese patients with CTDs to identify potentially disease-causing variations. Adults who tested negative for 22q11.2 deletions were recruited from the adult CHD clinic in Hong Kong. Using a stringent calling criteria, high-confidence CNV calls were obtained, and a large control set comprising 3,987 Caucasian and 1,945 Singapore Chinese subjects was used to identify rare CNVs. Ten large rare CNVs were identified, and 3 in 108 individuals were confirmed to harbour
CNVs. All three patients were syndromic with a more complex phenotype, and each of these CNVs overlapped regions likely to be important in CHD. One was a 611 kb deletion at 17p13.3, telomeric to the Miller-Dieker syndrome (MDS) critical region, overlapping the
gene. Another was a 5 Mb deletion at 13q33.3, within a previously described critical region for CHD. A third CNV, previously unreported, was a large duplication at 2q22.3 overlapping the
gene. The commonly reported 1q21.1 recurrent duplication was not observed in this Chinese cohort. We provide detailed phenotypic and genotypic descriptions of large rare genic CNVs that may represent CHD loci in the East Asian population. Larger samples of Chinese origin will be required to determine whether the genome-wide distribution differs from that found in predominantly European CHD cohorts.
BACKGROUNDThe emerging 3q13.31 microdeletion syndrome appears to encompass diverse neurodevelopmental conditions. However, the 3q13.31 deletion is rare and few adult cases have yet been reported. We ...examined a cohort with schizophrenia (n = 459) and adult control subjects (n = 26,826) using high-resolution microarray technology for deletions and duplications at the 3q13.31 locus. RESULTSWe report on the extended adult phenotype associated with a 3q13.31 microdeletion in a 41-year-old male proband with schizophrenia and a nonverbal learning disability. He was noted to have a speech impairment, delayed motor skills, and other features consistent with the 3q13.31 microdeletion syndrome. The 2.06 Mb deletion overlapped two microRNAs and seven RefSeq genes, including GAP43, LSAMP, DRD3, and ZBTB20. No overlapping 3q13.31 deletions or duplications were identified in control subjects. CONCLUSIONSLater-onset conditions like schizophrenia are increasingly associated with rare copy number variations and associated genomic disorders like the 3q13.31 microdeletion syndrome. Detailed phenotype information across the lifespan facilitates genotype-phenotype correlations, accurate genetic counselling, and anticipatory care.
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