4q27 deletion and 7q36.1 microduplication in a patient with multiple malformations and hearing loss: a case report

Abstract

Background: Chromosome deletions of the long arm of chromosome 4 in 4q syndrome are characterized by mild facial and digital dysmorphism, developmental delay, growth retardation, and skeletal and cardiac anomalies, which is regarded as an autism spectrum disorder. Moreover, some scarce reports indicate that patients with 4q interstitial deletion and 7p duplication may present symptoms associated with hearing loss. Case presentation: A boy with a severe developmental delay not only post-natal but also intrauterine and several dysmorphic features including microcephaly, ocular hypertelorism, exophthalmos, low-set ears, single palmar flexion crease, and overlapping toes presented discontinued cyanosis and recurrent respiratory infections. MRI, BAEP, echocardiogram and bronchoscopy revealed that he had persistent falcine sinus with a thin corpus callosum, left auditory pathway disorder, patent foramen ovale (2 mm), and tracheobronchomalacia with the right superior bronchus arising from the lateral posterior wall of the right main bronchus. Finally, the patient died with severe pneumonia at 10 months. Array CGH revealed a 23.62 Mb deletion at chromosome 4q27, arr [hg19] 4q27-q31.21 (121, 148, 089-144, 769, 263) × 1, and a 0.85 Mb duplication at chromosome 7q36.1, arr [hg19] 7q36.1-q36.2 (152, 510, 685-153, 363,5 98) × 3. It is rare for 4q syndrome cases or 7q duplications previously reported to have a hearing disorder, pulmonary dysplasia, and pulmonary arterial hypertension. Conclusions: The phenotype of our patient mainly reflects the effects of haploinsufficiency of FGF2, SPATA5, NAA15, SMAD1, HHIP genes combined with a microduplication of 7q36.1.

Identification and population genetic analyses of copy number variations in six domestic goat breeds and Bezoar ibexes using next-generation sequencing

“…For example, SPATA5 is a spermatogenesis-associated factor and is expressed specifically in the spermatogonia and spermatocytes [ 47 ]. A large deletion harboring SPATA5 was associated with multiple malformations and hearing loss in humans [ 48 ]. The KCNU1 gene, also known as SLO3 , is expressed only in mammalian testis and plays a vital role in male fertility [ 49 ].…”

Hearing Loss in Neurological Disorders

“…Genes with remarkably high risk accounting for these manifestations are listed in Table 2 . Most of them are involved in neuron and synaptic development ( Smith et al, 2002 ; Sinajon et al, 2015 ; Yang et al, 2015 ; Lahbib et al, 2019 ; Wu et al, 2020a ), among which only two genes are known to be auditory-related: ELMOD3 and FGF2 . ELMOD3 is involved in autosomal recessive non-syndromic deafness disability ( Lahbib et al, 2019 ), and FGF2 plays a role in the proliferation and survival of auditory neuroblasts ( Wu et al, 2020a ).…”

“…Most of them are involved in neuron and synaptic development ( Smith et al, 2002 ; Sinajon et al, 2015 ; Yang et al, 2015 ; Lahbib et al, 2019 ; Wu et al, 2020a ), among which only two genes are known to be auditory-related: ELMOD3 and FGF2 . ELMOD3 is involved in autosomal recessive non-syndromic deafness disability ( Lahbib et al, 2019 ), and FGF2 plays a role in the proliferation and survival of auditory neuroblasts ( Wu et al, 2020a ). Three monogenic disorders were reported to present with auditory dysfunction and ASD simultaneously, including Fragile X syndrome, MEIS2 syndrome, and ADNP syndrome ( Rotschafer et al, 2015 ; Douglas et al, 2018 ; Hacohen-Kleiman et al, 2019 ), related genes all function in brain development, and MEIS2 is responsible for the development of the inner ear in chicken ( Douglas et al, 2018 ).…”