First reported CABP2‐related non‐syndromic hearing loss in Northern Europe

Abstract

Background CABP2‐related non‐syndromic hearing loss have only been reported in a few families worldwide (Iran, Turkey, Pakistan and Italy). The hearing loss was in these cases described as prelingual, symmetrical, and moderate to severe. Methods Following DNA isolation, exome sequencing was performed in 123 genes related to non‐syndromic hearing loss. Variant verification and carrier testing were performed by direct sequencing. Results We report the first Northern European individual with CABP2‐related hearing loss: an 8‐year‐old Danish Caucasian boy with non‐syndromic, prelingual, and sensorineural hearing loss, who is homozygous for the splice site variant CABP2: c. 637+1G>T previously found in three Iranian families and in one Pakistani family. Both parents are of Danish Caucasian origin with no known history of consanguinity. This is in contrast to the four reported Middle Eastern families, who all were consanguineous. However, loss of heterozygosity in a 3.2 Mb area on chromosome 11 including CABP2 was observed, suggesting a common parental ancestor. Conclusion We report the first case of CABP2‐related autosomal recessive hearing loss in Northern Europe. The index is of Danish Caucasian origin and found to be homozygous for the splice site variant c.637+1G>T.

Identification of novel gene variants causing autosomal recessive non-syndromic hearing loss in Iranian families

“…Therefore, ophthalmological examinations are necessary for individuals with CABP2-related HL. However, no ocular pathology has been reported so far (Sheyanth et al, 2021). Regarding to our patient, no ophthalmologic complication has been found.…”

“…The CABP2 is a member of Ca 2+ -binding proteins (CABPs) subfamily with high similarity to calmodulin. This protein is expressed in the cochlea and modulates presynaptic calcium in ux in inner hair cells through voltage-gated calcium channels to regulate auditory sensitivity (Sheyanth et al, 2021). The frequency and spectrum of CABP2 mutations in most ethnic populations are mainly unknown.…”

A systematic review of the monogenic causes of Non‐Syndromic Hearing Loss (NSHL) and discussion of Current Diagnosis and Treatment options

“…66 The pathway also maintains the calcium channels found in hair cells, which stimulate synaptic transmission in ganglion neurons. 255 Ventral polarity in the inner ear and ventral otocyst development is controlled through Sonic hedgehog (Shh) signaling. 256 It is also responsible for neurogenesis of the inner ear and ventral growth of the otic vesicle.…”

“…Most of BMP pathway genes code for proteins which are essential for transport across cell membranes, encode the macromolecular protein networks among hair cells in the inner ear 254 and proteins that show expression in outer hair cells of the cochlea 66 . The pathway also maintains the calcium channels found in hair cells, which stimulate synaptic transmission in ganglion neurons 255 …”

Autosomal recessive nonsyndromic hearing impairment in two Finnish families due to the population enriched CABP2 c.637+1G>T variant

“…CABP2 ‐related ARNSHI has been reported in families from Iran ( N = 4) (Koohiyan et al, 2019 ; Schrauwen et al, 2012 ), Turkey ( N = 1) (Bademci et al, 2016 ), Italy ( N = 1) (Picher et al, 2017 ), Pakistan ( N = 1) (Richard et al, 2019 ), and Denmark ( N = 1) (Sheyanth et al, 2021 ). For five of these families, the CABP2 (NM_016366.3) c.637+1G>T is the causative variant (Iranian [ N = 3], Pakistani [ N = 1], and Danish [ N = 1]) (Table 1 ).…”