A Disease-Causing FRMD7 Variant in a Chinese Family with Infantile Nystagmus
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In this report, we described a large Han-Chinese family which presents with various phenotypes from unaffected to manifested nystagmus in females. Infantile nystagmus (IN) is characterized by bilateral, involuntary, and periodic eyeball oscillation, occurring at birth or within the first 6 months. The most common inheritance pattern of IN is an X-linked form with incomplete penetrance among females, and the FERM domain containing 7 gene (FRMD7) is a main disease-causing gene. A combination of exome sequencing and Sanger sequencing, as well as detailed clinical examinations were performed on the Chinese IN family. An FRMD7 c.47T>C (p.Phe16Ser) variant was proposed as the disease-causing variant. Incomplete penetrance was found in females with the FRMD7 c.47T>C variant, and hemizygous male affected subjects presented more severe manifestations compared to heterozygous female affected subjects. These findings could enhance genetic counseling and antenatal diagnosis of IN.
KeywordsInfantile nystagmus FERM domain containing 7 Disease-causing variant Phenotype difference
We thank the participating members and investigators for their cooperation and efforts in collecting the genetic information, clinical data, and DNA specimens.
This work was supported by the National Natural Science Foundation of China [81670216, 81800219, and 81873686], Natural Science Foundation of Hunan Province [2016JJ2166 and 2018JJ2660], Scientific Research Project of Health and Family Planning Commission of Hunan Province, China [B20180729, B20180760 and B20180834], and National-level College Students’ Innovative Training Plan Program, China .
Compliance with Ethical Standards
The study adhered to the tenets of the Declaration of Helsinki. The research protocol was approved by the Institutional Review Board of the Third Xiangya Hospital, Central South University (Changsha, China). All participants and their guardians have signed the written informed consent.
Conflict of Interest
The authors declare that they have no conflict of interest.
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