Zerkaoui Maria, Demain Leigh A M, Cherkaoui Jaouad Imane, Ratbi Ilham, Amjoud Karima, Urquhart Jill E, O'Sullivan James, Newman William G, Sefiani Abdelaziz
aCenter for Human Genomics, Faculty of Medicine and Pharmacy bDepartment of Endocrinology, Diabetology and Nutrition, Avicenna Hospital, Mohammed V University cDepartment of Medical Genetics, National Institute of Health, Rabat, Morocco dDivision of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester eManchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Clin Dysmorphol. 2017 Oct;26(4):200-204. doi: 10.1097/MCD.0000000000000198.
The objective of this study was to report the clinical and biological characteristics of two Perrault syndrome cases in a Moroccan family with homozygous variant c.1565C>A in the LARS2 gene and to establish genotype-phenotype correlation of patients with the same mutation by review of the literature. Whole-exome sequencing was performed. Data analysis was carried out and confirmed by Sanger sequencing and segregation. The affected siblings were diagnosed as having Perrault syndrome with sensorineural hearing loss at low frequencies; the female proband had primary amenorrhea and ovarian dysgenesis. Both affected individuals had a marfanoid habitus and no neurological features. Both patients carried the homozygous variant c.1565C>A; p.Thr522Asn in exon 13 of the LARS2 gene. This variant has already been reported as a homozygous variant in three other Perrault syndrome families. Both affected siblings of a Moroccan consanguineous family with LARS2 variants had low-frequency sensorineural hearing loss, marfanoid habitus, and primary ovarian insufficiency in the affected girl. According to the literature, this variant, c.1565C>A; p.Thr522Asn, can be correlated with low-frequency hearing loss. However, marfanoid habitus was been considered a nonspecific feature in Perrault syndrome, but we believe that it may be more specific than considered previously. This diagnosis allowed us to provide appropriate management to the patients and to provide more accurate genetic counseling to this family.
本研究的目的是报告一个摩洛哥家庭中两例患有LARS2基因纯合变异c.1565C>A的佩罗特综合征病例的临床和生物学特征，并通过文献复习建立具有相同突变的患者的基因型-表型相关性。进行了全外显子组测序。通过桑格测序和分离分析进行数据分析并予以确认。受影响的兄弟姐妹被诊断为患有佩罗特综合征，伴有低频感音神经性听力损失；女性先证者有原发性闭经和卵巢发育不全。两名受影响个体均有马方综合征体型且无神经学特征。两名患者均携带LARS2基因第13外显子的纯合变异c.1565C>A；p.Thr522Asn。该变异已在其他三个佩罗特综合征家族中被报告为纯合变异。一个具有LARS2变异的摩洛哥近亲家庭的两名受影响兄弟姐妹均有低频感音神经性听力损失、马方综合征体型，且患病女孩有原发性卵巢功能不全。根据文献，该变异c.1565C>A；p.Thr522Asn可能与低频听力损失相关。然而，马方综合征体型在佩罗特综合征中曾被认为是非特异性特征，但我们认为它可能比之前认为的更具特异性。这一诊断使我们能够为患者提供适当的管理，并为该家庭提供更准确的遗传咨询。
