A new case of 8q22.1 microdeletion restricts the critical region for Nablus mask‐like facial syndrome

Abstract

Microdeletions of 8q21.3-8q22.1 have been identified in all patients with Nablus mask-like facial syndrome (NMLFS). A recent report of a patient without this specific phenotype presented a 1.6 Mb deletion in this region that partially overlapped with previously reported 8q21.3 microdeletions, thus restricting critical region for this syndrome. We report on another case of an 8q21.3 deletion revealed by array comparative genome hybridization (aCGH) in a 4-year-old child with global developmental delay, autism, microcephaly, but without Nablus phenotype. The size of the interstitial deletion was estimated to span 5.2 Mb. By combining the data from previous reports on 8q21.3-8q22.1 deletions and our case, we were able to narrow the critical region of Nablus syndrome to 0.5 Mb. The deleted region includes FAM92A1, which seems to be a potential candidate gene in NMLFS.

Deletion of chromosome 8q22.1, a critical region for Nablus mask‐like facial syndrome: Four additional cases support a role of genetic modifiers in the manifestation of the phenotype

“…LINC00535 , a large intergenic non‐coding (linc) RNA, is deleted (either completely or partially) consistently in all 10 patients with the NMLFS phenotype and in 11 out of 13 patients without the phenotype. The two patients without deletion of LINC00535 have been reported by Jain et al [] and Debost‐Legrand et al [] (Fig…”

“…As reported by Allanson et al [], Debost‐Legrand et al [], and Overhoff et al [], the 1.84 Mb NMLFS critical region (chr8:94.43–96.27 Mb) is not sufficient to cause the NMLFS phenotype and full NMLFS phenotype may require contribution of additional unidentified genetic variant(s) and/or modifier(s). Upon combining the data from all the published reports [Shieh et al, ; Barber et al, ; Raas‐Rothschild et al, ; Jain et al, , Allanson et al, ; Debost‐Legrand et al, ; Overhoff et al, ], there are more than 20 genes that are consistently deleted in all 10 patients with the NMLFS phenotype (Fig…”

“…The Nablus mask‐like facial syndrome (NMLFS) is a rare microdeletion syndrome with a distinctive craniofacial appearance consisting of tight‐appearing glistening facial skin, blepharophimosis, telecanthus, sparse arched eyebrows, flat and broad nose, long philtrum, distinctive ears, upswept frontal hairline, short and broad neck, and developmental delay (OMIM: 608156) [Shieh et al, ; Raas‐Rothschild et al, ]. We read with great interest the articles by Allanson et al [] suggesting that deletion of chromosome 8q22.1 is necessary, but not sufficient for development of NMLFS, supplemented by additional patients reported by Debost‐Legrand et al [] and Overhoff et al [], which provide further refinement of the critical region. We report on four additional patients with deletion of chromosome 8q22.1, two of whom had characteristic clinical features of NMLFS while the others did not (Table ).…”

“…). Roles of these overlapping genes in the 8q22.1 deletion interval have been extensively discussed in the literature [Jain et al, ; Allanson et al, ; Debost‐Legrand et al, ] except for LINC00535 (RefSeq Accession: NR_033858.1) [Strausberg et al, ]. LINC00535 , a large intergenic non‐coding (linc) RNA, is deleted (either completely or partially) consistently in all 10 patients with the NMLFS phenotype and in 11 out of 13 patients without the phenotype.…”

Nablus syndrome: Easy to diagnose yet difficult to solve

“…Interestingly, these individuals include two mother–child pairs with a deletion of most or all of the critical region. Although one member of each pair is said to have mildly tight or thick skin, they lack the impairment of facial expression necessary for a diagnosis of Nablus syndrome (Table ; Allanson et al, ; Debost‐Legrand et al, ; Jain, Yang, & Farrell, ; Jamuar et al, ).…”