A new case with 10q23 interstitial deletion encompassing both PTEN and BMPR1A narrows the genetic region deleted in juvenile polyposis syndrome

Abstract

We report on a patient with a contiguous interstitial germline deletion of chromosome 10q23, encompassing BMPR1A and PTEN, with clinical manifestations of juvenile polyposis and minor symptoms of Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). The patient presented dysmorphic features as well as developmental delay at the age of 5 months. Multiple polyps along all parts of the colon were diagnosed at the age of 3 years, following an episode of a severe abdominal pain and intestinal bleeding. The high-resolution comparative genomic hybridisation revealed a 3.7-Mb deletion within the 10q23 chromosomal region: 86,329,859-90,035,024. The genotyping with four polymorphic microsatellite markers confirmed a de novo 10q deletion on the allele with a paternal origin, encompassing both PTEN and BMPR1A genes. The karyotype analysis additionally identified a balanced translocation involving chromosomes 5q and 7q, and an inversion at chromosome 2, i.e. 46,XY,t(5;7)(q13.3-q36), inv(2)(p25q34). Although many genetic defects were detected, it is most likely that the 10q23 deletion is primarily the cause for the serious phenotypic manifestations. The current clinical findings and deletion of BMPR1A indicate a diagnosis of severe juvenile polyposis, but the existing macrocephaly and PTEN deletion also point to either CS or BRRS, which cannot be ruled out at the moment because of their clinical manifestation later in life and the de novo character of the deletion. The deletion detected in our patient narrows the genetic region deleted in all reported cases with juvenile polyposis by 0.04 Mb from the telomeric side, mapping it to the region chr10:88.5-90.03Mb (GRCh37/hg19), with an overall length of 1.53 Mb.

Gcap14 is a microtubule plus-end-tracking protein coordinating microtubule–actin crosstalk during neurodevelopment

“…Moreover, 10qdel syndrome is accompanied by macrocephaly with symptoms of autism and epilepsy ( 58 – 60 ). The genes encoding PTEN and bone morphogenetic protein receptor type 1A in this genomic region have been suggested as the culprits, but the molecular basis of 10qdel syndrome has not been clearly elucidated ( 61 , 62 ). Given that Gcap14 deficiency causes neurodevelopmental defects with thickening of the cortex reminiscent of macrocephaly seen in 10qdel syndromes, it is intriguing to speculate the contribution of Gcap14 deficiency to the 10qdel syndromes.…”

SHH medulloblastoma and very early onset of bowel polyps in a child with PTEN hamartoma tumor syndrome

“… a Our case; b Lachlan et al (2007) ; c Tsuchiya et al (1998) ; d Gorensek et al (1984) ; e Hiljadnikova Bajro et al (2013) ; DD, developmental delay; M, male; PHTS, PTEN hamartoma tumor syndrome. …”

Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi-Society Task Force on Colorectal Cancer

“…This leads to the loss of both PTEN and BMPR1A 28 ; a situation that can also look like BRRS, also known as juvenile polyposis of infancy (see section on JPS). 110,111 In a smaller study of 19 patients with CS (in which only 12 were shown to have germline pathogenic variants in PTEN), pancolonic polyps were found in 58%, pan-gastrointestinal polyps in 42%, and the pathological interpretation of the polyps included inflammatory polyps in 95%, but also adenomas, lipomas, and ganglioneuromas. 112 Moreover, there was more than 1 pathological variety in 79% of patients, indicating the clinical heterogeneity in this entity.…”

“…This leads to the loss of both PTEN and BMPR1A 28 ; a situation that can also look like BRRS, also known as juvenile polyposis of infancy (see section on JPS). 110,111…”