Delineation of the 9q31 deletion syndrome: Genomic microarray characterization of two patients with overlapping deletions

Abstract

Interstitial deletions of chromosome 9q31 are very rare. The deletions in most reported patients have been detected by conventional cytogenetics, with reported breakpoints ranging between 9q21 and 9q34. Therefore, an accurate description of a "9q31 deletion syndrome" could not be established.However, based on microarray studies, a small region of overlap has recently been proposed.We report clinical features of two unrelated individuals with overlapping 9q deletions identified by SNP microarray analysis. Patient 1 has a 9 Mb deletion, while Patient 2's deletion was 21.6 Mb. The clinical features common to our patients and those in the literature include developmental delay and short stature. Patient 2 shows additional features not reported in other 9q31 deletions, such as hearing loss, ventriculomegaly, cleft lip and palate, and small kidneys, which could be due to the larger size of the deletion, hence the influence of the genes in the region beyond the smallest region of overlap. Based on the comparison of these patients with the previously reported patients, we redefine the smallest region of overlap and characterize the clinical features of the 9q31 deletion syndrome. K E Y W O R D S 9q31 deletion, developmental delay, multiple congenital anomalies, short stature, SNP microarray

Pregnancy Outcome and Postnatal Chromosome Analysis of the Cord Blood and Chorionic Villi in Two Cases after Intrauterine Transfer of Mosaic Aneuploid Blastocysts

“…Long-arm monosomy of chromosome 9 indicates foetal mortality. Partial deletion of the long arm of chromosome 9 has been reported to cause foetal hydrops, severe developmental delay, cardiac disease, and respiratory failure [ 9 ]. Partial deletion of the long arm of chromosome 14 has been associated with holoprosencephaly, microcephaly, and facial malformations [ 10 ].…”

Further characterization of the 9q31 microdeletion phenotype; delineation of a common region of overlap containing ZNF462

“…We present three patients with intellectual disability/global developmental delay and craniofacial dysmorphisms with interstitial deletions of the 9q31 chromosome region. Deletions in this region are relatively uncommon and there have been less than three dozen cases reported in the literature (Cao et al, 2015; Chien et al, 2010; Dugan et al, 2018; Gamerdinger et al, 2008; Iivonen et al, 2021; Mucciolo et al, 2014; Ramineni et al, 2019; Xu et al, 2013) and DECIPHER database (Firth et al, 2009) (DECIPHER ID: 270439, 250,887, 261,011, 253,228, 256,779, 286,220, 280,899, 252,795, 267,903, 296,377, 248,259, 274,871, 359,751, 394,934, 402,156, 402,516) (Figure 2). Common craniofacial dysmorphisms in this cohort include bilateral ptosis, arched eyebrows, a broad nasal root, low forehead, low set ears, anteverted nares, palate abnormalities, and a long philtrum.…”

“…Emerging information about one of these interstitial microdeletions (9q31) suggests that the haploinsufficiency of this region may cause a recognizable microdeletion syndrome. To date there have been several cases reported in the literature (Cao et al, 2015; Chien et al, 2010; Dugan et al, 2018; Gamerdinger et al, 2008; Iivonen et al, 2021; Mucciolo et al, 2014; Ramineni et al, 2019) and over a dozen additional cases recorded in DECIPHER (Firth et al, 2009). These cases share many phenotypic similarities such as developmental delay/intellectual disability, hearing loss, short stature/growth retardation, microcephaly (<10th percentile) and distinctive facial features of ptosis, arched eyebrows, and ear malformations.…”

Kallmann syndrome in a patient with Weiss–Kruszka syndrome and a de novo deletion in 9q31.2

“…A summary of the patients is presented in Supplementary Table 2. The figure is modified from ( 14 ). The deletion coordinates are presented as GRCh37 (hg19).…”

“…To date, 25 patients with Weiss–Kruszka syndrome have been reported ( 3 , 4 , 5 , 6 ), yet delayed puberty, anosmia, or CHH are not among the listed phenotypic features. On the other hand, deletions in the 9q31.2 chromosomal area have been continuously described since the 1970s ( 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ), at least one of whom had CHH ( 11 ), olfactory bulb hypoplasia ( 14 ), or delayed puberty in multiple family members ( 15 ), and at least four had cleft lip or palate ( 8 , 10 , 13 , 14 ), that is, phenotypic features reminiscent of KS. However, no clear link between the 9q31.2 deletions and complete KS currently exists.…”