ClinGen Dosage Sensitivity Curation Page

15q25.2 recurrent region (LCR B-C, proximal)

  • Curation Status: Complete
  • id: ISCA-37500
  • Date last evaluated: 2016-10-13
  • Issue Type: ClinGen Region Curation
  • ClinGen Haploinsufficiency Score: 3
  • ClinGen Triplosensitivity Score: 0

Location Information

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Evidence for haploinsufficiency phenotype
PubMed ID Description
24352913 Burgess et al (2013) described three patients who helped to define the phenotypic features of individuals with de novo 15q25.2 microdeletions. They stated the core phenotypic features are mild to moderate developmental delay or intellectual disability, postnatal short stature, anemia, and cryptorchidism in males. There is no consistent facial dysmorphism. The presence of four low-copy repeat clusters (LCRs A-D) likely predispose this region to genomic rearrangements via non-allelic homologous recombination. Recurrent deletions within the 15q25.2 region might include only the proximal (B-C) or both proximal and distal regions (B-D). However, there does not appear to be any distinctive phenotypic differences between patients carrying only the 1.5 Mb proximal deletion (LCRB and LCRC) versus patients carrying a deletion involving both proximal and distal breakpoints (LCRB through LCRD).
23166063 Palumbo et al (2012) suggested that 15q25.2 microdeletion is an emerging syndrome characterized by a distinct, although variable spectrum of clinical manifestations, including mild dysmorphic features, neurodevelopmental delay, and a recognizable pattern of congenital malformation. The suggested that the behavioral phenotype is characterized by hyperactivity, anxiety, and autistic features. Their patient was an 8 y.o. girl with severe speech and psychomotor delay, behavioral problems, and mild dysmorphic features. She had a 1.6 Mb deletion in the 15q25.2 region (LCRs B-C). Parental testing revealed that this was a de novo deletion on the maternal allele. The coordinates for the minimally deleted region are 83,169,537 to 84,828,339.
17847001 Wagenstaller et al (2007) studied 67 children with unexplained mental retardation with normal karyotypes using a 100K array. Eleven various CNVs were found in this cohort. One patient's CNV was a de novo 1.37 Mb microdeletion at 15q25.2 (maximal coordinates of this deletion include LCRs B-C). She had very mild dysmorphism. Her primary findings were psychomotor retardation, polysplenia, and a hypoproliferative macrocytic anemia that developed in the first year of life and that required blood transfusion until she was 4 years old. Due to her short stature and anemia, the diagnosis of Diamond-Blackfan anemia was considered. At age 11, she was referred to the emergency ward for bleeding from esophageal varices. Ultrasound revealed a severe portal vein stenosis, but the liver structure was normal.
  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

Wat et al (2010) also described 15q25.2 microduplications in two patients. However, one of the patients also had a 22q11.2 microdeletion. And the other patient's 15q25.2 microduplication was proven to be paternally inherited from her unaffected father. No consistent phenotype has been found to be associated with a microduplication of this region.