ClinGen Dosage Sensitivity Curation Page

10q22.3q23.2 recurrent region (LCR-3/4-flanked) (includes BMPR1A)

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
20345475 Alliman et al. (2010) provide a clinical description of four individuals with 7.25 Mb deletions spanning 10q22.3q23.2 (hg18 81.7-88.9 Mb). Deletions were identified by oligo microarray analysis and were flanked by LCRs. Parental FISH results indicated that these deletions were apparently de novo in all four patients. Common phenotypic features include: developmental delay, language delay, and dysmorphic features (such as hypertelorism and low-set ears).
21248748 van Bon et al. (2011) summarize five individuals with deletions spanning 10q22.3q23.2 (hg18 81.6-89.1 Mb, liftover hg19 81.6-89.1 Mb). Deletions were identified by various oligo microarray platforms. They were subsequently fine-mapped using a custom high-resolution array and were flanked by LCR3/4. One patient had an additional de novo CNV and another patient had a 47,XYY karyotype. The 10q22.3q23.3 deletion was found to be de novo in 3/5 cases, inherited from a mother who underwent special-schooling in one case, and of unknown inheritance in the last case. Common phenotypic features include: developmental delay, speech delay, and dysmorphic features (such as hypertelorism and low-set ears). Other anomalies were sometimes observed (e.g. cardiac findings, brain findings, hand abnormalities).
24550761 Petrova et al. (2014) report a case of a boy with a de novo LCR3/4-flanked 10q22.3q23.2 deletion who was determined to have age-appropriate language development at age 2 years 3 months. The boy had a congenital heart defect, a club foot, cleft palate, hypertelorism, and other dysmorphic features.

Evidence for Triplosenstive Phenotype

Evidence for triplosensitivity phenotype
PubMed ID Description
21248748 van Bon et al. (2011) also summarize two unrelated patients with duplications spanning 10q22.3q23.2 (hg18 81.6-89.1 Mb, liftover hg19 81.6-89.1 Mb). Duplications were identified by various oligo microarray platforms. They were subsequently fine-mapped using a custom high-resolution array and were flanked by LCR3/4. In one patient the 10q22.3q23.2 duplication was de novo and this patient had an additional de novo CNV. The other patient inherited the 10q22.3q23.2 duplication (parental phenotype not available). Common phenotypic features include: developmental delay, and dysmorphic features (such as deep set eyes and thin upper lip).
26383923 Tang et al. (2015) report a boy with an apparently de novo 10q22.3q23.2 duplication (hg19 80.6-88.7 Mb) observed by both chromosome analysis and SNP microarray. His phenotype included: funnel chest, difficulty pronouncing words, atrial septal defect, growth retardation, a head circumference <3rd centile, and dysmorphic features (including a thin upper lip).

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.