A Brazilian case of IFAP syndrome with severe congenital ichthyosis and limb malformations caused by a rare variant in MBTPS2 / Um caso brasileiro de síndrome IFAP com ictiose congênita grave e malformações de membros causadas por uma variante rara em MBTPS2

Abstract Objective: The classic triad, which defines IFAP syndrome, is ichthyosis follicularis, alopecia, and photophobia. It is a rare X-linked genetic disorder characterized by multiple congenital anomalies with variable severity, caused by pathogenic variants in the MBTPS2 gene, which encodes a zinc metalloprotease that is essential for normal development. This study aimed to report a case of a Brazilian patient with IFAP syndrome presenting skeletal anomalies, which is a rare finding among patients from different families. Case description: We describe a male proband with IFAP syndrome showing severe ichthyosis congenita, cryptorchidism, limb malformation, and comprising the BRESHECK syndrome features. Using whole-exome sequencing, we identified a rare missense variant in hemizygosity in the MBTPS2 gene, which had not been identified in other family members. Comments: This is the first diagnosis of IFAP syndrome in Brazil with a molecular investigation. The present case study thus expands our knowledge on the mutational spectrum of MBPTS2 associated with IFAP syndrome.

RESUMO Objetivo: A clássica tríade de ictiose folicular, alopecia e fotofobia dá nome a uma síndrome rara de origem genética com herança ligada ao cromossomo X (síndrome IFAP, do inglês Ichthyosis Follicularis, Alopecia, and Photophobia). Esta é uma síndrome caracterizada por múltiplas anomalias congênitas de expressividade variável, causada por variantes patogênicas no gene MBTPS2, que codifica uma zinco-metaloprotease essencial para o desenvolvimento normal humano. O objetivo deste estudo é apresentar o relato de caso de um paciente brasileiro com síndrome IFAP que apresentou anomalias esqueléticas, um achado raro entre os pacientes de diferentes famílias. Descrição do caso: Apresentamos um probando do sexo masculino com síndrome IFAP, com ictiose congênita grave, criptorquidia, malformação de membros e as características da síndrome de BRESHECK. Por meio do sequenciamento do exoma completo, identificamos uma variante rara do tipo missense, em hemizigose, no gene MBTPS2, não identificada em outros membros da família. Comentários: Este é o primeiro diagnóstico de síndrome IFAP no Brasil com investigação molecular. A análise molecular e a descrição de uma variante rara no gene MBPTS2 expandem nosso conhecimento sobre o espectro mutacional desse gene associado à síndrome IFAP.

Holt-Oram syndrome: a rare case report.

Holt-Oram syndrome is an inherited disorder that causes abnormalities of the hands, arms and heart. The diagnosis can be established clinically. The diagnostic criteria have been validated with molecular testing. An upper-limb malformation involving the carpal bone(s) and, variably, the radial and/or thenar bones-An abnormal carpal bone, present in all affected individuals and identified by performing a posterior-anterior hand x-ray, may be the only evidence of disease. 24 years unbooked Hindu female G2P1+0 presented in OPD at term. Her USG examination showed-small deformed upper limbs with poorly appreciable upper limb skeleton. Induction of labour was done and patient delivered vaginally a female baby with deformed upper limbs. This case emphasizes the importance of proper history taking (family history), early diagnosis of such anomalies and proper counseling the parents.

EFFECT OF DIFFERENT CONCENTRATION OF TRICHOSTATIN A ON CHICKEN WING BUD DEVELOPMENT / 解剖学报

Objective To investigate the reaction of the limbs treated with different concentration of Trichostatin A(75?mol/L,750 ?mol/L,1.5mmol/L),a histone deacetylase(HDAC)-inhibitor.This may be useful to improve our understanding of the role of chromatin remodelling and epigenetic control of gene expression patterns and ultimately the development of drugs against cancer. Methods Using the chicken embryonic limb as an experimental model.The embryos received grafts of TSA soaked beads or PBS control beads into the right forelimb buds.Then they were submitted to in situ hybridization with probes and apoptosis test.Results TSA could modulate the expression of some myogenesis related genes,MyoD and Myf5 during chicken myogenesis.Using apoptosis staining methods,there was no significant apoptosis in the TSA(75?mol/L) treated embryos.However the induction of morphological changes and apoptosis at specific stage was possible with high concentration of TSA.Conclusion TSA(75?mol/L) regulates certain important transcriptional targets and strongly control muscle differentiation.Increasing the concentration of TSA(≥750?mol/L) can induce apoptosis and embryonic limb malformations.Chicken limb development can serve as a convenient in vivo model for studying the effect of HDAC inhibitors.