New CDH3 mutation in the first Spanish case of hypotrichosis with juvenile macular dystrophy, a case report

• Published in: BMC medical genetics Vol. 18; no. 1; p. 1
• Main Authors: Blanco-Kelly, Fiona, Rodrigues-Jacy da Silva, Luciana, Sanchez-Navarro, Iker, Riveiro-Alvarez, Rosa, Lopez-Martinez, Miguel Angel, Corton, Marta, Ayuso, Carmen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07.01.2017; BioMed Central
• Subjects: Age; ATP-Binding Cassette Transporters - genetics; Biopsy; Cadherins - genetics; Case Report; Gene mutations; Genetic aspects; Genetic testing; Genetics; Humans; Hyperplasia; Hypotrichosis - congenital; Hypotrichosis - genetics; Macular degeneration; Macular Degeneration - genetics; Male; Mutation; Pedigree; Risk factors; Skin; Stem cells; Visual acuity; Young Adult; United States; Case report; Syndromic retinal dystrophy; CDH3; Hypotrichosis; Macular dystrophy
• ISSN: 1471-2350; 1471-2350
• 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.