Blanco-Kelly Fiona, Rodrigues-Jacy da Silva Luciana, Sanchez-Navarro Iker, Riveiro-Alvarez Rosa, Lopez-Martinez Miguel Angel, Corton Marta, Ayuso Carmen
Department of Medical Genetics, Instituto de Investigación Sanitaria - Fundación Jiménez Díaz, (IIS-FJD, UAM), Madrid, Spain.
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto Carlos IIII (ISCIII), Madrid, Spain.
BMC Med Genet. 2017 Jan 7;18(1):1. doi: 10.1186/s12881-016-0364-5.
CDH3 on 16q22.1 is responsible for two rare autosomal recessive disorders with hypotrichosis and progressive macular dystrophy: Hypotrichosis with Juvenile Macular Dystrophy and Ectodermal Dysplasia, Ectrodactyly and Macular Dystrophy. We present a new case of Hypotrichosis with Juvenile Macular Dystrophy.
A Spanish male born in 1998 from non-consanguineous healthy parents with a suspected diagnosis of Keratosis Follicularis Spinulosa Decalvans and Retinitis Pigmentosa Inversa referred to our Genetics Department (IIS-Fundación Jiménez Díaz). Molecular study of ABCA4 was performed, and a heterozygous missense p.Val2050Leu variant in ABCA4 was found. Clinical revision reclassified this patient as Hypotrichosis with Juvenile Macular Dystrophy. Therefore, further CDH3 sequencing was performed showing a novel maternal missense change p.Val205Met (probably pathogenic by in silico analysis), and a previously reported paternal frameshift c.830del;p.Gly277Alafs*20, thus supporting the clinical diagnosis..
This is not only the first Spanish case with this clinical and molecular diagnosis, but a new mutation has been described in CDH3. Moreover, this work reflects the importance of joint assessment of clinical signs and evaluation of pedigree for a correct genetic study approach and diagnostic.
位于16q22.1的CDH3基因与两种罕见的常染色体隐性疾病相关，这两种疾病分别为毛发稀少伴进行性黄斑营养不良：青少年黄斑营养不良性毛发稀少症，以及外胚层发育不良、缺指（趾）畸形和黄斑营养不良。我们报告了一例青少年黄斑营养不良性毛发稀少症的新病例。
一名1998年出生的西班牙男性，其父母非近亲结婚且身体健康，最初疑似诊断为棘状毛囊角化病和反相性色素性视网膜炎，后来转诊至我们的遗传学部门（IIS-希门尼斯·迪亚斯基金会）。对ABCA4基因进行了分子研究，发现ABCA4基因存在一个杂合错义p.Val2050Leu变异。临床复查将该患者重新分类为青少年黄斑营养不良性毛发稀少症。因此，进一步对CDH3基因进行测序，结果显示母亲存在一个新的错义改变p.ValMet（通过计算机分析可能具有致病性），父亲存在一个先前报道的移码突变c.830del；p.Gly277Alafs*20，从而支持了临床诊断。
这不仅是首例具有这种临床和分子诊断的西班牙病例，而且在CDH3基因中发现了一个新的突变。此外，这项工作反映了联合评估临床体征和系谱评估对于正确的遗传研究方法和诊断的重要性。
