Further phenotype description, genotype characterization in patients with de novo interstitial deletion on 2p23.2–24.1

Abstract

Interstitial deletions of the distal part of chromosome 2p seem to be rarely identified or reported: to date, only nine distinct patients have been published. The last three patients were diagnosed with the use of more recent molecular karyotyping technology (SNP array). We report on the natural history of an 8-year-old boy with dysmorphic features, postnatal overgrowth, microcephaly, generalized hypotonia, and global developmental delay. The diagnosis was accomplished by SNP array investigation that led to the identification of a de novo 7.4 Mb deletion of 2p23.2-p24.1. The present patient also developed a nonsyndromic auditory neuropathy. Since the deletion encompassed the OTOF gene, this haploinsufficiency suggests second allele sequencing as a possible cause (DFNB9). We describe the phenotype of the patient and review reports in patients with del 2p23 subsequent to the advent of the genomic era. At the time of identification of "new" micro- deletion and -duplication syndromes, the present report adds to the description of phenotype in patients with del(2)p(23.2;24.1) and the 2p23.2 region in particular.

PTRHD1(C2orf79) mutations lead to autosomal-recessive intellectual disability and parkinsonism

“…Despite PTRHD1 mutations having never been reported in parkinsonism or ID, deletions at the 2p23 locus, encompassing the PTRHD1 gene, are known to be associated with several ID syndromes (Supporting Table 2) . Furthermore, Jaberi and colleagues recently identified a missense PTRHD1 mutation (c.155G>A; p.Cys52Tyr) in a family with early‐onset parkinsonism and cognitive dysfunction .…”

“…Despite PTRHD1 mutations having never been reported in parkinsonism or ID, deletions at the 2p23 locus, encompassing the PTRHD1 gene, are known to be associated with several ID syndromes (Supporting Table 2). [14][15][16][17][18][19][20] Furthermore, Jaberi and colleagues recently identified a missense PTRHD1 mutation (c.155G>A; p.Cys52Tyr) in a family with early-onset parkinsonism and cognitive dysfunction. 21 Although they claimed that the strongest candidate gene for the disease was ADORA1 attributed to the role of adenosine receptors in brain function and neuronal activity, there were no substantial proofs to discard PTRHD1 as a causative gene, as was well acknowledged in their report.…”

Tatton–Brown–Rahman syndrome due to 2p23 microdeletion

“…The size of deletion was smaller in our patient (1.5‐Mb) compared with other 2p23 deletion patients. Bloch et al [] reviewed the patients with an interstitial deletion encompassing the 2p23 region and showed that postnatal overgrowth was a common feature in the four patients with small deletions detected by SNP‐array.…”

“…Rocca et al [] reported an interstitial de novo 3.9‐Mb deletion of the 2p23.2‐p23.3 segment, detected by SNP‐array analysis, in a 5‐year‐old boy showing hypotonia, overweight, dysmorphic facial features, and cryptorchidism. Bloch et al [] reported an 8‐year‐old boy with dysmorphic features, postnatal overgrowth, microcephaly, generalized hypotonia, and global developmental delay. A de novo 7.4‐Mb deletion of 2p23.2‐p24.1 was identified by SNP array.…”

“…A de novo 7.4‐Mb deletion of 2p23.2‐p24.1 was identified by SNP array. Bloch et al [] reviewed the patients and showed that postnatal overgrowth was a common feature. However, the association of DNMT3A haploinsufficiency was not clearly mentioned.…”