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Evidence of genetic heterogeneity in Alberta Hutterites with Usher syndrome type I.

Zhou Q, Lenger C, Smith R, Kimberling WJ, Ye M, Lehmann O, MacDonald I - Mol. Vis. (2012)

Bottom Line: Single nucleotide polymorphic linkage analysis was then used to confirm another locus, and DNA was analyzed with the Usher Chip v4.0 platform.Severe hearing impairment, unintelligible speech, and retinitis pigmentosa with varying degrees of visual acuity and visual field loss established a clinical diagnosis of Usher syndrome type I.The patients did not carry the exon 10 mutation in the PCDH15 gene; however, with microarray analysis, a previously reported mutation (c.52C>T; p.Q18X) in the myosin VIIA (MYO7A) gene was found in the homozygous state in the affected siblings.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Peking Union Medical College, Beijing, China.

ABSTRACT

Purpose: To identify the genetic defect in a Hutterite population from northern Alberta with Usher syndrome type I.

Methods: Complete ophthalmic examinations were conducted on two boys and two girls from two related Hutterite families diagnosed with Usher syndrome type I. DNA from patients and their parents was first evaluated for a mutation in exon 10 of the protocadherin-related 15 (PCDH15) gene (c.1471delG), previously reported in southern Alberta Hutterite patients with Usher syndrome (USH1F). Single nucleotide polymorphic linkage analysis was then used to confirm another locus, and DNA was analyzed with the Usher Chip v4.0 platform.

Results: Severe hearing impairment, unintelligible speech, and retinitis pigmentosa with varying degrees of visual acuity and visual field loss established a clinical diagnosis of Usher syndrome type I. The patients did not carry the exon 10 mutation in the PCDH15 gene; however, with microarray analysis, a previously reported mutation (c.52C>T; p.Q18X) in the myosin VIIA (MYO7A) gene was found in the homozygous state in the affected siblings.

Conclusions: The finding of a MYO7A mutation in two related Hutterite families from northern Alberta provides evidence of genetic heterogeneity in Hutterites affected by Usher syndrome type I.

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Related in: MedlinePlus

Pedigree of Hutterite families. MYO7A mutation c.57C>T (-), normal allele (+).
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f1: Pedigree of Hutterite families. MYO7A mutation c.57C>T (-), normal allele (+).

Mentions: Two boys and two girls from two related Hutterite families were diagnosed with Usher syndrome (Figure 1). All four patients had prelingual, bilateral sensorineural hearing loss, and delayed development of walking in early childhood. The pure tone audiometry results from individual II:4 showed hearing thresholds of 25, 60, 75, 75, and 80 dB at 0.25, 0.5, 1, 2, and 4 kHz, respectively, in the right ear, and 35, 65, 75, 55, and 65 dB in the left ear. There was no change in the thresholds one year later. The patients did not develop intelligible speech, and hearing aids were not effective. At the time of referral, all showed evidence of RP. Individuals II:1 and II:2 showed bilateral nasal loss of the visual field, and bone spicules in the nasal fundus at the age of 18 and 10, respectively. Subject II:3 showed bilateral bone spicules in the fundus, and only 20 degrees of visual field was preserved in both eyes by age 13. Subject II:4 showed bilateral nasal loss of the visual field and bone spicules in both eyes at age 9. The ocular findings of the Hutterite patients from northern Alberta are listed in Table 1. Characteristic Goldmann visual fields and fundus photographs are shown in Figure 2 and Figure 3, respectively. The patients’ parents all had normal fundus examinations and normal visual fields. While asymptomatic, no formal tests of balance and hearing were obtained.


Evidence of genetic heterogeneity in Alberta Hutterites with Usher syndrome type I.

Zhou Q, Lenger C, Smith R, Kimberling WJ, Ye M, Lehmann O, MacDonald I - Mol. Vis. (2012)

Pedigree of Hutterite families. MYO7A mutation c.57C>T (-), normal allele (+).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369897&req=5

f1: Pedigree of Hutterite families. MYO7A mutation c.57C>T (-), normal allele (+).
Mentions: Two boys and two girls from two related Hutterite families were diagnosed with Usher syndrome (Figure 1). All four patients had prelingual, bilateral sensorineural hearing loss, and delayed development of walking in early childhood. The pure tone audiometry results from individual II:4 showed hearing thresholds of 25, 60, 75, 75, and 80 dB at 0.25, 0.5, 1, 2, and 4 kHz, respectively, in the right ear, and 35, 65, 75, 55, and 65 dB in the left ear. There was no change in the thresholds one year later. The patients did not develop intelligible speech, and hearing aids were not effective. At the time of referral, all showed evidence of RP. Individuals II:1 and II:2 showed bilateral nasal loss of the visual field, and bone spicules in the nasal fundus at the age of 18 and 10, respectively. Subject II:3 showed bilateral bone spicules in the fundus, and only 20 degrees of visual field was preserved in both eyes by age 13. Subject II:4 showed bilateral nasal loss of the visual field and bone spicules in both eyes at age 9. The ocular findings of the Hutterite patients from northern Alberta are listed in Table 1. Characteristic Goldmann visual fields and fundus photographs are shown in Figure 2 and Figure 3, respectively. The patients’ parents all had normal fundus examinations and normal visual fields. While asymptomatic, no formal tests of balance and hearing were obtained.

Bottom Line: Single nucleotide polymorphic linkage analysis was then used to confirm another locus, and DNA was analyzed with the Usher Chip v4.0 platform.Severe hearing impairment, unintelligible speech, and retinitis pigmentosa with varying degrees of visual acuity and visual field loss established a clinical diagnosis of Usher syndrome type I.The patients did not carry the exon 10 mutation in the PCDH15 gene; however, with microarray analysis, a previously reported mutation (c.52C>T; p.Q18X) in the myosin VIIA (MYO7A) gene was found in the homozygous state in the affected siblings.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Peking Union Medical College, Beijing, China.

ABSTRACT

Purpose: To identify the genetic defect in a Hutterite population from northern Alberta with Usher syndrome type I.

Methods: Complete ophthalmic examinations were conducted on two boys and two girls from two related Hutterite families diagnosed with Usher syndrome type I. DNA from patients and their parents was first evaluated for a mutation in exon 10 of the protocadherin-related 15 (PCDH15) gene (c.1471delG), previously reported in southern Alberta Hutterite patients with Usher syndrome (USH1F). Single nucleotide polymorphic linkage analysis was then used to confirm another locus, and DNA was analyzed with the Usher Chip v4.0 platform.

Results: Severe hearing impairment, unintelligible speech, and retinitis pigmentosa with varying degrees of visual acuity and visual field loss established a clinical diagnosis of Usher syndrome type I. The patients did not carry the exon 10 mutation in the PCDH15 gene; however, with microarray analysis, a previously reported mutation (c.52C>T; p.Q18X) in the myosin VIIA (MYO7A) gene was found in the homozygous state in the affected siblings.

Conclusions: The finding of a MYO7A mutation in two related Hutterite families from northern Alberta provides evidence of genetic heterogeneity in Hutterites affected by Usher syndrome type I.

Show MeSH
Related in: MedlinePlus