Dysmorphism and immunodeficiency - One of the differential diagnoses is PAX1 related otofaciocervical syndrome type 2
We report a female child born to a consanguineous couple with homozygous PAX1 variant. She was diagnosed with T cell immunodeficiency as a neonate and underwent haematopoietic stem cell transplant with cord blood at the age of 5 months. She had facial dysmorphism including ear abnormalities and spinal deformity. We present longitudinal follow-up of the proband who has responded well to the bone marrow transplant to add to the otherwise limited description of this rare condition. This case report expands on the limited literature available on this condition, with only five families reported to date and it further highlights...
Source: European Journal of Medical Genetics - May 20, 2022 Category: Genetics & Stem Cells Authors: Charlotte Sherlaw-Sturrock Thomas Austin Julia Baptista Kimberly Gilmour Swati Naik Source Type: research

Involvement of cranial nerves in ATTR Ile127Val amyloidosis
Eur J Med Genet. 2022 May 14:104524. doi: 10.1016/j.ejmg.2022.104524. Online ahead of print.ABSTRACTThe involvement of cranial nerves is rare in ATTR amyloidosis. However, involvement has occasionally been reported in the p.Val50Met variant, the most commonly studied worldwide. On the other hand, in ATTR p.Ile127Val, an uncommon variant, the cranial nerves IX, X, and XII, are frequently involved. Here, we present a series of cases of ATTR Ile107Val amyloidosis, in which the involvement of multiple cranial nerves V, VII, IX, X, XI, and XII seems to be routinely included in phenotypic manifestations in different phases of cl...
Source: European Journal of Medical Genetics - May 17, 2022 Category: Genetics & Stem Cells Authors: Jemima A da Silva Batista Luiza R Carrera Adriele R F Viriato Marco Ant ônio C Novaes Renato Jos é L de Morais Francisco T O Oliveira Wilson Marques Marcela C âmara Machado-Costa Source Type: research

Involvement of cranial nerves in ATTR Ile127Val amyloidosis
Eur J Med Genet. 2022 May 14:104524. doi: 10.1016/j.ejmg.2022.104524. Online ahead of print.ABSTRACTThe involvement of cranial nerves is rare in ATTR amyloidosis. However, involvement has occasionally been reported in the p.Val50Met variant, the most commonly studied worldwide. On the other hand, in ATTR p.Ile127Val, an uncommon variant, the cranial nerves IX, X, and XII, are frequently involved. Here, we present a series of cases of ATTR Ile107Val amyloidosis, in which the involvement of multiple cranial nerves V, VII, IX, X, XI, and XII seems to be routinely included in phenotypic manifestations in different phases of cl...
Source: European Journal of Medical Genetics - May 17, 2022 Category: Genetics & Stem Cells Authors: Jemima A da Silva Batista Luiza R Carrera Adriele R F Viriato Marco Ant ônio C Novaes Renato Jos é L de Morais Francisco T O Oliveira Wilson Marques Marcela C âmara Machado-Costa Source Type: research

Involvement of cranial nerves in ATTR Ile127Val amyloidosis
Eur J Med Genet. 2022 May 14:104524. doi: 10.1016/j.ejmg.2022.104524. Online ahead of print.ABSTRACTThe involvement of cranial nerves is rare in ATTR amyloidosis. However, involvement has occasionally been reported in the p.Val50Met variant, the most commonly studied worldwide. On the other hand, in ATTR p.Ile127Val, an uncommon variant, the cranial nerves IX, X, and XII, are frequently involved. Here, we present a series of cases of ATTR Ile107Val amyloidosis, in which the involvement of multiple cranial nerves V, VII, IX, X, XI, and XII seems to be routinely included in phenotypic manifestations in different phases of cl...
Source: European Journal of Medical Genetics - May 17, 2022 Category: Genetics & Stem Cells Authors: Jemima A da Silva Batista Luiza R Carrera Adriele R F Viriato Marco Ant ônio C Novaes Renato Jos é L de Morais Francisco T O Oliveira Wilson Marques Marcela C âmara Machado-Costa Source Type: research

Deciphering the molecular landscape of microcephaly in 87 Indian families by exome sequencing
We present data of 91 patients from 87 unrelated families referred to our clinic during 2016-2020 and provide a comprehensive clinical and genetic landscape in the studied cohort. Molecular diagnosis using exome sequencing was made in 45 families giving a yield of 51.7%. In 9 additional families probable causative variants were detected. We identified disease causing variations in 49 genes that are involved in different functional pathways Among these, 36 had an autosomal recessive pattern, 8 had an autosomal dominant pattern (all inherited de novo), and 5 had an X-linked pattern. In 41 probands where sequence variations i...
Source: European Journal of Medical Genetics - May 14, 2022 Category: Genetics & Stem Cells Authors: Suzena Masih Amita Moirangthem Arya Shambhavi Archana Rai Kausik Mandal Deepti Saxena Mayank Nilay Neha Agrawal Somya Srivastava Haseena Sait Shubha R Phadke Source Type: research

Steel syndrome: Report of three patients, including monozygotic twins and review of clinical and mutation profiles
We describe for the first time, cleft palate and delayed carpal bone ossification as features of Steel syndrome. We reviewed clinical features in all mutation-proven Steel syndrome patients. Short stature and dislocation/subluxation of hip joint are consistently observed. Other features include dislocated radial heads, scoliosis, lordosis, carpal coalition, facial dysmorphism, hearing loss, bilateral fifth finger clinodactyly, knee deformities and developmental delay. Seven missense variants and eight null variants are reported in COL27A1 until date. We also looked into the genotype-phenotype correlation in Puerto Rican an...
Source: European Journal of Medical Genetics - May 14, 2022 Category: Genetics & Stem Cells Authors: Katta M Girisha Prince Jacob Gandham SriLakshmi Bhavani Hitesh Shah Geert R Mortier Source Type: research

Deciphering the molecular landscape of microcephaly in 87 Indian families by exome sequencing
We present data of 91 patients from 87 unrelated families referred to our clinic during 2016-2020 and provide a comprehensive clinical and genetic landscape in the studied cohort. Molecular diagnosis using exome sequencing was made in 45 families giving a yield of 51.7%. In 9 additional families probable causative variants were detected. We identified disease causing variations in 49 genes that are involved in different functional pathways Among these, 36 had an autosomal recessive pattern, 8 had an autosomal dominant pattern (all inherited de novo), and 5 had an X-linked pattern. In 41 probands where sequence variations i...
Source: European Journal of Medical Genetics - May 14, 2022 Category: Genetics & Stem Cells Authors: Suzena Masih Amita Moirangthem Arya Shambhavi Archana Rai Kausik Mandal Deepti Saxena Mayank Nilay Neha Agrawal Somya Srivastava Haseena Sait Shubha R Phadke Source Type: research

Report of three patients, including monozygotic twins and review of clinical and mutation profiles
We describe for the first time, cleft palate and delayed carpal bone ossification as features of Steel syndrome. We reviewed clinical features in all mutation-proven Steel syndrome patients. Short stature and dislocation/subluxation of hip joint are consistently observed. Other features include dislocated radial heads, scoliosis, lordosis, carpal coalition, facial dysmorphism, hearing loss, bilateral fifth finger clinodactyly, knee deformities and developmental delay. Seven missense variants and eight null variants are reported in COL27A1 until date. We also looked into the genotype-phenotype correlation in Puerto Rican an...
Source: European Journal of Medical Genetics - May 14, 2022 Category: Genetics & Stem Cells Authors: Katta M Girisha Prince Jacob Gandham SriLakshmi Bhavani Hitesh Shah Geert R Mortier Source Type: research

Deciphering the molecular landscape of microcephaly in 87 Indian families by exome sequencing
We present data of 91 patients from 87 unrelated families referred to our clinic during 2016-2020 and provide a comprehensive clinical and genetic landscape in the studied cohort. Molecular diagnosis using exome sequencing was made in 45 families giving a yield of 51.7%. In 9 additional families probable causative variants were detected. We identified disease causing variations in 49 genes that are involved in different functional pathways Among these, 36 had an autosomal recessive pattern, 8 had an autosomal dominant pattern (all inherited de novo), and 5 had an X-linked pattern. In 41 probands where sequence variations i...
Source: European Journal of Medical Genetics - May 14, 2022 Category: Genetics & Stem Cells Authors: Suzena Masih Amita Moirangthem Arya Shambhavi Archana Rai Kausik Mandal Deepti Saxena Mayank Nilay Neha Agrawal Somya Srivastava Haseena Sait Shubha R Phadke Source Type: research

Report of three patients, including monozygotic twins and review of clinical and mutation profiles
We describe for the first time, cleft palate and delayed carpal bone ossification as features of Steel syndrome. We reviewed clinical features in all mutation-proven Steel syndrome patients. Short stature and dislocation/subluxation of hip joint are consistently observed. Other features include dislocated radial heads, scoliosis, lordosis, carpal coalition, facial dysmorphism, hearing loss, bilateral fifth finger clinodactyly, knee deformities and developmental delay. Seven missense variants and eight null variants are reported in COL27A1 until date. We also looked into the genotype-phenotype correlation in Puerto Rican an...
Source: European Journal of Medical Genetics - May 14, 2022 Category: Genetics & Stem Cells Authors: Katta M Girisha Prince Jacob Gandham SriLakshmi Bhavani Hitesh Shah Geert R Mortier Source Type: research

Glycogen Storage Disease type IA refractory to cornstarch: Can next generation sequencing offer a solution?
Eur J Med Genet. 2022 May 9:104518. doi: 10.1016/j.ejmg.2022.104518. Online ahead of print.ABSTRACTAvoidance of fasting and regular ingestion of uncooked-cornstarch have long been the mainstay dietary treatment of Glycogen Storage Disease type Ia (GSD-Ia). However, GSD-Ia patients who despite optimal dietary treatment show poor glycemic control and are intolerant to cornstarch, present a complex clinical challenge. We pursued Whole Exome Sequencing (WES) in three such unrelated patients, to both confirm a molecular diagnosis of GSD-Ia, and seek additional variants in other genes (e.g. genes associated with amylase producti...
Source: European Journal of Medical Genetics - May 13, 2022 Category: Genetics & Stem Cells Authors: Or Steg Saban Ben Pode-Shakked Bassam Abu-Libdeh Maya Granot Galia Barkai Yael Haberman Inon Roterman Avishay Lahad Dror S Shouval Batia Weiss Dina Marek-Yagel Ortal Barel Nurit Loberman-Nachum Smadar Abraham Raz Somech David A Weinstein Yair Anikster Source Type: research

Glycogen Storage Disease type IA refractory to cornstarch: Can next generation sequencing offer a solution?
Eur J Med Genet. 2022 May 9:104518. doi: 10.1016/j.ejmg.2022.104518. Online ahead of print.ABSTRACTAvoidance of fasting and regular ingestion of uncooked-cornstarch have long been the mainstay dietary treatment of Glycogen Storage Disease type Ia (GSD-Ia). However, GSD-Ia patients who despite optimal dietary treatment show poor glycemic control and are intolerant to cornstarch, present a complex clinical challenge. We pursued Whole Exome Sequencing (WES) in three such unrelated patients, to both confirm a molecular diagnosis of GSD-Ia, and seek additional variants in other genes (e.g. genes associated with amylase producti...
Source: European Journal of Medical Genetics - May 13, 2022 Category: Genetics & Stem Cells Authors: Or Steg Saban Ben Pode-Shakked Bassam Abu-Libdeh Maya Granot Galia Barkai Yael Haberman Inon Roterman Avishay Lahad Dror S Shouval Batia Weiss Dina Marek-Yagel Ortal Barel Nurit Loberman-Nachum Smadar Abraham Raz Somech David A Weinstein Yair Anikster Source Type: research

Do paternal deletions involving the FOXF1 locus on chromosome 16q24.1 manifest with more severe non-lung anomalies?
Eur J Med Genet. 2022 May 6:104519. doi: 10.1016/j.ejmg.2022.104519. Online ahead of print.ABSTRACTAlveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disorder in neonates due to heterozygous loss-of-function of the mesenchymal transcription factor gene, FOXF1. Interestingly, unlike ACDMPV-causing point mutations in FOXF1 that can be inherited from the mother or father, causative copy-number variant (CNV) deletions arise de novo and almost exclusively on chromosome 16 inherited from the mother (n = 50 vs. n = 3). Here, we describe a fourth case of a de novo paterna...
Source: European Journal of Medical Genetics - May 9, 2022 Category: Genetics & Stem Cells Authors: Esra Y ıldız Bölükbaşı Justyna A Karolak Tomasz Gambin Przemyslaw Szafranski Gail H Deutsch Pawe ł Stankiewicz Source Type: research

Do paternal deletions involving the FOXF1 locus on chromosome 16q24.1 manifest with more severe non-lung anomalies?
Eur J Med Genet. 2022 May 6:104519. doi: 10.1016/j.ejmg.2022.104519. Online ahead of print.ABSTRACTAlveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disorder in neonates due to heterozygous loss-of-function of the mesenchymal transcription factor gene, FOXF1. Interestingly, unlike ACDMPV-causing point mutations in FOXF1 that can be inherited from the mother or father, causative copy-number variant (CNV) deletions arise de novo and almost exclusively on chromosome 16 inherited from the mother (n = 50 vs. n = 3). Here, we describe a fourth case of a de novo paterna...
Source: European Journal of Medical Genetics - May 9, 2022 Category: Genetics & Stem Cells Authors: Esra Y ıldız Bölükbaşı Justyna A Karolak Tomasz Gambin Przemyslaw Szafranski Gail H Deutsch Pawe ł Stankiewicz Source Type: research

Do paternal deletions involving the FOXF1 locus on chromosome 16q24.1 manifest with more severe non-lung anomalies?
Eur J Med Genet. 2022 May 6:104519. doi: 10.1016/j.ejmg.2022.104519. Online ahead of print.ABSTRACTAlveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disorder in neonates due to heterozygous loss-of-function of the mesenchymal transcription factor gene, FOXF1. Interestingly, unlike ACDMPV-causing point mutations in FOXF1 that can be inherited from the mother or father, causative copy-number variant (CNV) deletions arise de novo and almost exclusively on chromosome 16 inherited from the mother (n = 50 vs. n = 3). Here, we describe a fourth case of a de novo paterna...
Source: European Journal of Medical Genetics - May 9, 2022 Category: Genetics & Stem Cells Authors: Esra Y ıldız Bölükbaşı Justyna A Karolak Tomasz Gambin Przemyslaw Szafranski Gail H Deutsch Pawe ł Stankiewicz Source Type: research