Infantile onset spinocerebellar ataxia caused by compound heterozygosity for Twinkle mutations and modeling of Twinkle mutations causing recessive disease.
Infantile onset spinocerebellar ataxia caused by compound heterozygosity for Twinkle mutations and modeling of Twinkle mutations causing recessive disease.
Exceptions to this include DFNB2 (MYO7A), DFNB8/10 (TMPRSS3) and DFNB16 (STRC) where age of onset may sometimes be later on in childhood, DFNB4 (SLC26A4) where there may be dilated vestibular aqueducts and endolymphatic sacs, and DFNB9 (OTOF) where there may also be an associated auditory neuropathy.
Furthermore, we found another two TIMM8A variations, the deletion c.133_135delGAG and a copy number variation (CNV) including the TIMM8A gene, in two independent case, when we performed NGS on an auditory neuropathy population.
Exceptions to this include DFNB2 (MYO7A), DFNB8/10 (TMPRSS3) and DFNB16 (STRC) where age of onset may sometimes be later on in childhood, DFNB4 (SLC26A4) where there may be dilated vestibular aqueducts and endolymphatic sacs, and DFNB9 (OTOF) where there may also be an associated auditory neuropathy.
Here, we report bi-allelic pathogenic SPTBN4 variants (three homozygous and two compound heterozygous) that cause a severe neurological syndrome that includes congenital hypotonia, intellectual disability, and motor axonal and auditory neuropathy.
Homozygous SLITRK6 c.1240C>T (p.Gln414Ter) nonsense mutations are associated with high myopia, cochlear dysfunction attributed to outer hair cell disease, and progressive auditory neuropathy.
Exceptions to this include DFNB2 (MYO7A), DFNB8/10 (TMPRSS3) and DFNB16 (STRC) where age of onset may sometimes be later on in childhood, DFNB4 (SLC26A4) where there may be dilated vestibular aqueducts and endolymphatic sacs, and DFNB9 (OTOF) where there may also be an associated auditory neuropathy.
The DFNB59 gene has been identified recently, and two missense mutations (p.R183W and p.T54I) have been shown to cause auditory neuropathy in both humans and transgenic mice.
Non-syndromic hearing impairment caused by mutations of DFNB59 (encoding pejvakin) has been described in a couple of families in which affected individuals presented with either auditory neuropathy or hearing loss of cochlear origin.
Here we report on DFNB59, a newly identified gene on chromosome 2q31.1-q31.3 mutated in four families segregating autosomal recessive auditory neuropathy.
Pure monosomy and pure trisomy of 13q21.2-31.1 consequent to a familial insertional translocation: exclusion of PCDH9 as the responsible gene for autosomal dominant auditory neuropathy (AUNA1).
Exceptions to this include DFNB2 (MYO7A), DFNB8/10 (TMPRSS3) and DFNB16 (STRC) where age of onset may sometimes be later on in childhood, DFNB4 (SLC26A4) where there may be dilated vestibular aqueducts and endolymphatic sacs, and DFNB9 (OTOF) where there may also be an associated auditory neuropathy.
Nine different mutations of OTOF were detected, and seven of them were novel. p.R1939Q, which was previously reported in one family in the United States, was found in 13 of the 23 patients (56.5%), and a founder effect was determined for this mutation. p.R1939Q homozygotes and compound heterozygotes of p.R1939Q and truncating mutations or a putative splice site mutation presented with stable, and severe-to-profound hearing loss with a flat or gently sloping audiogram, whereas patients who had non-truncating mutations except for p.R1939Q presented with moderate hearing loss with a steeply sloping, gently sloping or flat audiogram, or temperature-sensitive auditory neuropathy.
Screening revealed that mutations in the OTOF gene account for AN in 4 of 73(5.5%) sporadic AN patients, which shows a lower genetic load of that gene in contrast to the previous studies based on other populations.
Thus, the present study aimed to investigate molecular changes in the OTOF gene in patients with auditory neuropathy, and to develop a DNA chip for the molecular diagnosis of auditory neuropathy using mass spectrometry for genotyping.